Abnormalities of tetrahydrobiopterin metabolism
Apr. 07, 2024
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Propionyl-CoA carboxylase deficiency
- Updated 11.30.2023
- Released 02.07.1994
- Expires For CME 11.30.2026
Propionyl-CoA carboxylase deficiency
Introduction
Overview
The author explains that individuals with propionic acidemia are surviving into adolescence and adulthood; therefore, we are beginning to see additional complications of the disorder, such as psychiatric problems, optic neuropathy, and chronic renal failure in some of them.
Key points
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• Propionyl-CoA carboxylase deficiency or propionic acidemia, an inherited metabolic disorder, is due to deficient propionyl-CoA carboxylase activity and usually presents during infancy and early childhood with neurologic symptoms, metabolic acidosis, hyperammonemia, and organic aciduria. | |
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• Although propionyl-CoA carboxylase is a biotin-dependent enzyme, individuals with the disorder do not usually respond to biotin therapy. | |
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• Individuals with propionic acidemia are usually treated with a protein-restricted, high-carbohydrate diet and carnitine supplementation. | |
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• Children with propionic acidemia can be identified by mass spectroscopy on newborn screening, but they are also identified by the characteristic organic aciduria during infancy or childhood when they are symptomatic. |
Historical note and terminology
In 1961, a patient was described with ketosis and increased plasma glycine concentrations and was designated as having idiopathic hyperglycinemia (40; 134). The name of the disorder was subsequently changed to "ketotic hyperglycinemia" to distinguish it from disorders with hyperglycinemia without ketosis. Some patients excreted high concentrations of methylmalonic acid and were considered to have methylmalonic acidemia, whereas others excreted high concentrations of propionate derivatives in their urine and were considered to have propionic acidemia (163; 12). In 1968, a patient with propionic acidemia was found to have increased excretion of hydroxypropionate and odd-numbered carbon-chain fatty acids (78). These findings suggested that propionic acidemia was due to a defect in the conversion of propionyl-CoA to methylmalonyl-CoA. In 1969, the absence of propionate oxidation was demonstrated in the peripheral blood leukocytes of the sibling of the first patient described with ketotic hyperglycinemia (79). The next year, deficient propionyl-CoA carboxylase activity was shown in the fibroblasts of an affected patient (80). Propionyl-CoA carboxylase deficiency was shown in the liver extracts of another patient (64). Subsequently, more than 100 children with propionic acidemia have been reported. The human enzyme has been purified to homogeneity, the cDNA encoding for both of its two subunits have been sequenced, and various molecular mutations have been identified.
Clinical manifestations
Presentation and course
Propionic acidemia has been extensively reviewed (210). The symptoms and clinical complications of propionic acidemia are variable (205; 162; 61; 77; 139; 68; 148). Symptoms usually occur immediately after birth or in the first few weeks or months of life but may not occur until several years of age. The initial symptoms are usually nonspecific and include feeding problems, vomiting, hypotonia, lethargy, and dehydration. The infant may exhibit generalized or myoclonic seizures and hepatomegaly. Symptomatic children may not have acidosis (150). One child presented with ketolactic acidosis and hyperglycemia mimicking diabetic ketoacidosis (57). Some patients have presented with tachypnea, constipation, hypothermia, and jaundice. Several children with propionic acidemia have experienced visual hallucinations (174).
Thrombocytopenia, with and without petechiae or purpura, or neutropenia and pancytopenia have been seen in propionic acidemia, especially in the severely ill infant. Multiple children have exhibited optic atrophy (82; 119). One newborn presented with E coli sepsis (199). Chronically ill patients often have mild hypochromic normocytic anemia. Frequently, respiratory or gastrointestinal infections precipitate symptoms and metabolic compromise. An increasing number of children with propionic acidemia are exhibiting sensorineural hearing loss (26). Affected children may progress rapidly to coma. In a review of 49 symptomatic children with propionic acidemia who were diagnosed by selective testing, most exhibited symptoms during the first three months of life, and about one third died (165). The use of different therapeutic strategies is a probable explanation for the variation in outcomes. Rapid diagnosis and supportive intervention are essential for preventing irreversible brain damage.
Symptoms of children with propionic acidemia who present in early childhood are similar to those that present in the newborn period or infancy. The seizures in childhood tend to be generalized or of absence type, with a few exhibiting focal seizures. One patient exhibited dysautonomia (76). It is common for affected individuals to have recurrent episodes of metabolic compromise due to infections, increased protein intake, or immunologic abnormalities (127).
Some patients appear to be more prone to infection. There may not, however, be an obvious predisposing condition for metabolic compromise. One child developed skin lesions that suggested acrodermatitis enteropathica (51).
Growth retardation is common. A number of patients exhibited osteoporosis on radiographic examination.
An increasing number have had evidence of cardiomyopathy (120; 117; 85; 156). The latter can be rapidly fatal. In a review of 10 children with propionic acidemia, most exhibited cardiac electrophysiological abnormalities, including prolonged QTc intervals, arrhythmias, reduced left ventricular function, and dilated cardiomyopathy (89; 17; 87; 22; 56; 100; 50). Cardiomyopathies and long QT intervals are common in older individuals with propionic acidemia in the Amish population (58). Some of these cardiac abnormalities are life-threatening, and early preventive intervention must be considered. The cardiomyopathies observed in individuals with propionic acidemia may be reversible with orthotopic liver transplantation (161; 192). A study has shown that high-dose coenzyme Q10 supplementation may be a potential adjuvant therapeutic to be considered in propionic acidemia-related cardiomyopathy (16).
As the individuals with propionic acidemia are living longer, it has been observed that many exhibit liver disease, such as fibrosis and cirrhosis (83). This was evident by elevations of serum alpha-fetoprotein.
Hearing loss has been described in some individuals with propionic acidemia, and there is evidence that the accumulated metabolites in untreated disease may cause long QT syndrome by inhibiting the KvLQT1/KCNE1 channel complex (66).
Individual patients have exhibited recurrent acute pancreatitis (27), cerebral infarction (90), and late-onset optic neuropathy (201). One child was described as having autism spectrum disorder (10; 202; 49).
Hyperechogenic nephromegaly has been reported in a child with propionic acidemia (21).
A rare finding in an affected infant was hemophagocytic lymphohistiocytosis (99).
A milder form of propionic acidemia has been reported in Japan, with the children exhibiting mild mental retardation or extrapyramidal symptoms, occasionally with metabolic acidosis (215).
EEGs are frequently abnormal (205; 181). Slow delta waves and loss of normal alpha rhythm may be due to hyperammonemia. The changes may vary from mild nonspecific abnormalities to grossly aberrant generalized or focal (temporal) patterns. Individuals with propionic acidemia appear to be prone to cortical dysfunction, which can result in background and epileptiform activity and a high frequency of clinical seizures (71). These individuals may also exhibit stroke-like episodes (168) and cerebral hemorrhage (194), especially during metabolic decompensation. MRI or CT scan of the head may indicate cerebral edema, ventricular dilation or cerebral atrophy, lucencies (leukoencephalopathy), and delayed myelination (62; 24; 20; 05). These findings, if persistent, appear to indicate poor prognosis. Transient basal ganglia lucencies were seen on CT scans following episodes of metabolic compromise in affected individuals who presented after the newborn period. No abnormalities were found in the concentration of neurotransmitters in the cerebrospinal fluid of these patients. An increasing number of patients have developed symptoms of basal ganglia lesions including variable degrees of dementia; extrapyramidal tract symptoms, such as dystonia, choreoathetosis, and rigidity; and acute infarction in the absence of metabolic compromise (70; 74; 143; 133; 09).
One infant with propionic acidemia had spontaneous resolution of his basil ganglia lesions (25). Magnetic resonance spectroscopy has been used to study metabolic alterations in affected children who are metabolically stable (38).
In a survey of 20 patients with propionic acidemia, 11 initially developed symptoms during the first week of life, and nine developed symptoms after the newborn period; those who presented earlier had a higher mortality rate than those who presented later (184). Moreover, all the early-onset patients were retarded, and three had mild chorea and dystonia. Four individuals in the late-onset group had movement disorders. One 31-year-old man with propionyl-CoA carboxylase deficiency initially presented with adult-onset chorea and dementia (110; 170). In a review of the long-term follow-up of 19 children with propionic acidemia by a French group, the prognosis was in general poor, although aggressive treatment did prevent death in many children with neonatal onset of symptoms (164). Other studies indicate more favorable outcomes when there is good dietary compliance (188; 132). Autistic behaviors have been described in children with propionic acidemia (202).
Some patients with propionic acidemia have grown and developed normally on a protein-restricted diet. Several patients have had above average intelligence. In fact, one individual, who was detected because her brother had symptoms, has remained asymptomatic (207). One asymptomatic, healthy adult presented initially with dilated cardiomyopathy (105). Most affected children have some degree of developmental delay. A review of over 128 children with propionic acidemia, most of whom have had mutation analysis, reveals that those who have null mutations are more likely to have had severe clinical courses, whereas those who have missense mutations are more likely to have had later onset of symptoms and milder clinical courses (144). A consortium of clinical metabolic specialists reviewed the natural history of individuals with propionic acidemia (140).
Several adolescents have exhibited acute psychotic episodes, including hallucinations, panic, and disorganized behavior, for up to several months. Although these individuals had moderate metabolic compromise at the beginning of an episode, the psychiatric symptoms lasted longer (48).
An enzyme-deficient child developed rhabdomyolysis 1 to 2 weeks after a metabolic crisis (97). This was likely due to defective energy production caused by secondary mitochondrial dysfunction.
There are reports of children who suddenly deteriorated after minor infections, with and without metabolic acidosis or low plasma carnitine concentrations, and died from arrhythmias even though supportive therapy was rapidly administered (115). These examples suggest that cardiac complications are associated with this disorder.
Several children have exhibited optic neuropathy (13). Several children have exhibited renal failure in early infancy; and others have had chronic renal failure (93; 195).
Individuals with propionic acidemia identified by newborn screening appear to have a lower mortality rate than those found symptomatically; however, no clear benefit was demonstrated for the surviving individuals with regards to their clinical course, including the number of metabolic compromise episodes, physical and cognitive development and long-term complications (67). Even with the advances in management of propionic acidemia, in a study of 55 pediatric and adolescent individuals with disorder, most exhibited long-term neurocognitive impairment and complications affecting multiple organ systems (68).
Prognosis and complications
Early diagnosis and treatment is essential for better outcomes; however, it is still difficult to predict overall outcomes in this disorder (92). Some patients develop hypoxia and shock, especially in the newborn period. Many patients who have been diagnosed and aggressively treated soon after birth still experience frequent episodes of metabolic compromise, growth delay, neurologic sequelae, mental retardation, and cardiac complications, such as arrhythmias or death.
Clinical vignette
A 3-day-old male infant had vomiting, lethargy, and hypotonia. After several hours, the infant developed generalized myoclonic seizures. An arterial blood gas revealed a pH of 7.20 with a bicarbonate concentration of 10 mEq/L and a base deficit of 24. There was marked hyperammonemia. A complete blood count revealed neutropenia and mild thrombocytopenia. Plasma amino acid analysis revealed an elevated glycine concentration, and urinary organic acid analysis showed hydroxypropionate and methylcitrate, consistent with a diagnosis of propionic acidemia. The infant was treated with intravenous fluids and gradually improved. Although dialysis was considered for the hyperammonemia, it was not started because the ammonia concentration decreased, the ketones cleared from the urine, and the child became more alert and active. Over the next several days, the child was given increasing amounts of a protein-restricted diet, particularly restricting the amino acids, isoleucine, threonine, and valine. The infant was given a trial of biotin, which was ultimately considered to be of no benefit. Propionyl-CoA carboxylase deficiency was confirmed by enzyme assay in extracts of peripheral blood leukocytes and in cultured fibroblasts. The child has thrived on a protein-restricted formula, with occasional episodes of metabolic compromise when stressed with an infection. Over the years, the child has had mild developmental delay.
Biological basis
Etiology and pathogenesis
Propionic acidemia is due to a deficiency of propionyl-CoA carboxylase activity (64; 80). The deficiency is inherited as an autosomal recessive trait. Genetic complementation studies using heterokaryons formed from the pair-wise fusion of fibroblasts from patients with propionyl-CoA carboxylase deficiency have revealed two major groups, pccA and pccBC; the latter is further divided into the pccB and pccC subgroups (65; 203). Heterozygotes of the pccA group have about 50% of mean normal activity in leukocytes and fibroblasts, whereas heterozygotes of the pccBC group have normal enzyme activity (208). Human propionyl-CoA carboxylase has been purified to homogeneity, and the enzyme protein has been characterized in many patients (135). The cDNA for the two subunits of propionyl-CoA carboxylase, alpha (to which the biotin is covalently bound) and beta, have been cloned and sequenced (102; 107; 29). The alpha and beta subunits have been localized to chromosome 13q32 and 3q13.3-22, respectively (102; 96). Individuals with propionyl-CoA carboxylase deficiency belonging to the pccA complementation group have defects in the alpha subunit, and those belonging to the pccBC complementation group have defects in the beta subunit (106; 137). Various mutations in both the alpha and beta subunits of the enzyme causing propionic acidemia have been elucidated (108; 187; 136; 138; 154; 30; 31; 129; 155; 190; 152; 43; 98; 215; 141; 142; 44; 53; 212; 52; 101; 193; 39; 69; 182; 157; 08; 198; 113; 116). The effects of some of these mutations on enzyme activity and subunit assembly and stability have been studied (128; 41). Different mutations in the same beta-subunit may exhibit intragenic complementation due to stabilization of the subunits, thereby partially correcting the loss of enzyme activity (159). Studies of several mutations in the beta-subunit have revealed that the assembled abnormal enzymes have reduced activity and decreased thermostability but normal molecular mass and secondary structure (88). This suggests that propionic acidemia due to these and similar mutations may be amenable to chaperone therapy. As yet, there is no correlation between the residual enzyme activity, complementation groups, or mutation and the clinical features of the disorder. In a report of two children who were diagnosed with propionic academia, exome sequencing failed to identify a pathogenic variant of the PCCC genes (103). Genomic sequencing did demonstrate homozygous intronic variants of PCCB. Additionally, RNA analysis revealed that this variant created a pseudoexon with a premature stop codon. This case demonstrates the strength of genomic sequencing and RNA analysis in determining the pathogenicity of challenging cases.
Most individuals with propionic acidemia have been shown to have missense mutations in either the PCCA or PCCB gene. However, multiple patients with propionyl-CoA carboxylase deficiency have not been found to have a detectable alteration in one or both of their alleles. Of these, several have now been shown to have relatively large deletions of the PCCA gene that were not detected by routine sequencing (94; 54).
Propionyl-CoA carboxylase is a mitochondrial enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA, which subsequently is metabolized to succinyl-CoA that enters the tricarboxylic acid cycle. Propionyl-CoA is formed from the catabolism of several branched-chain amino acids, isoleucine, threonine, methionine, and valine, the oxidation of odd-numbered carbon-chain fatty acids, and the 3-carbon side chain of cholesterol. Enzyme activity is present in most human tissues, including the liver, brain, kidney, skin fibroblasts, and peripheral blood leukocytes and lymphoblasts.
Propionic acidemia usually presents with various degrees of metabolic acidosis, hyperammonemia, and ketosis. Patients have been symptomatic with and without acidosis, hyperammonemia, or ketosis (196; 162). The metabolic acidosis is usually accompanied by an increased anion gap and lactate elevations. The ketosis is due to the accumulation of abnormal organic acid metabolites of propionate in blood and beta-hydroxypropionate, methylcitrate, hydroxyvalerate, propionylglycine, tiglylglycine, acetoacetate, and beta-hydroxybutyrate in urine (205). Hyperammonemia plays a major role in causing the lethargy, somnolence, and coma seen in the disorder (171; 206). The hyperammonemia is due to the secondary inhibition of N-acetyl-glutamate synthetase, which produces N-acetylglutamate, the activator of carbamyl phosphate synthetase in the urea cycle (45). Hyperglycinemia is often seen particularly in infants, but its etiology and effects are not well understood (171; 11). Patients usually develop serum carnitine deficiency due to the conjugation of propionyl derivatives with carnitine and the urinary excretion of these acylcarnitines. Prior to treatment, the urinary ratio of the concentrations of acylcarnitine to free carnitine is greatly elevated. Hypoglycemia is not common in the disorder, unless there is severe metabolic compromise or impending death (211). Liver and kidney functions are usually normal, unless there is kidney failure from severe metabolic compromise or dehydration.
Two children, one infant and one adolescent, exhibited MRI findings of diffuse cortical or subcortical restriction with volume loss or vermian atrophy. The authors suggested that these unique radiological findings may help the radiologist to suggest the diagnosis.
Thrombocytopenia, neutropenia, or pancytopenia is probably due to the effect of abnormal organic acids on bone marrow (185; 183). These abnormalities or hypogammaglobulinemia caused by decreased protein intake may predispose affected individuals to infection. Anemia is probably due to nutritional deficits or frequent blood drawing.
Growth retardation is likely due to decreased protein intake or to repeated episodes of metabolic compromise that require hospitalization or restricted protein for various lengths of time. Plasma L-arginine and L-valine concentrations in individuals with propionic acidemia and the protein-to-energy prescription ratio are positively associated with height (123). Optimizing these plasma amino acid concentrations is critical in achieving normal growth and increasing protein tolerance.
Individuals with propionic acidemia may also be prone to develop secondary mitochondrial or respiratory chain deficiencies (197), such as a functional defect of coenzyme Q (59).
At autopsy, the brains of affected individuals have shown demyelination, swelling, spongy degeneration, and Alzheimer II cells (175; 205; 19). Livers have shown fatty infiltration, swollen hepatocytes, and degeneration. The fatty infiltration is likely due to carnitine deficiency because hepatomegaly usually resolves following carnitine supplementation.
Epidemiology
The exact incidence and prevalence of propionic acidemia are not known, but it is one of the most common organic acidemias. In 1973, amino acid screening of 350,000 newborns in Massachusetts detected only one patient with propionic acidemia on the basis of hyperglycinuria (111). This certainly represents an underestimation of the true incidence.
Prevention
Newborn screening for propionic acidemia is possible using electrospray tandem mass spectroscopy (173). With the incorporation of this technology into an increasing number of newborn screening programs, propionic acidemia should be diagnosed more rapidly and treatment initiated sooner. False-positive newborn screening results are common because the test is designed to identify elevation of C3 or propionylcarnitine metabolites. Second-tier measurement of 3-OH-propionic acid in the same blood spots can reduce the false-positive rate (104; 03).
Prenatal diagnosis of propionic acidemia is possible. Propionyl-CoA carboxylase can be determined in amniocytes and chorionic villi (63; 186; 32). 14C-propionate incorporation into trichloroacetic acid material in amniocytes has also been performed (200), but there was a reported discrepancy when the procedure was carried out in chorionic villi (131). Direct enzymatic assay in combination with molecular mutation analysis in chorion villi has been shown to be a rapid and reliable method of prenatal diagnosis (145). Abnormal concentrations of methylcitrate can be measured by isotope dilution assay or by gas-liquid chromatography of amniotic fluid (55; 86; 84). Methylcitrate is undetectable in normal amniotic fluid, but it is detectable and greatly increased in fluid from affected fetuses as early as 11 weeks' gestation. Prenatal diagnosis of propionic acidemia has also been performed by measuring elevated concentrations of propionylcarnitine in amniotic fluid (172). Measurement of the metabolites in amniotic fluid is advantageous; results can be obtained in several days, the samples can be easily transported to appropriate diagnostic centers without deterioration, and there is no risk of maternal contamination of amniocytes, as has been described. Prenatal diagnosis should be performed by a laboratory with experience. Preimplantation genetic diagnosis was successful in the delivery of healthy twins (02).
Differential diagnosis
Nonspecific clinical symptoms, including vomiting, hypotonia, and seizures, are often characteristic of treatable disorders, such as sepsis, gastrointestinal obstruction, and cardiorespiratory problems. After exclusion of these conditions, or when these findings are accompanied by metabolic ketoacidosis or hyperammonemia, the presence of an inborn error of metabolism should be considered. Both holocarboxylase synthetase deficiency and biotinidase deficiency may present initially with these clinical features, and both conditions have been misdiagnosed as other disorders before they were correctly identified (200).
Most affected children have metabolic acidosis and large anion gaps with elevated concentrations of lactate in serum and urine, although not all do (01). An amino acid analysis may reveal hyperglycinemia, which is also found in other organic acidemias, such as the methylmalonic acidemias and isovaleric acidemia and nonketotic hyperglycinemia. The latter is not accompanied by organic acidemia; nevertheless, propionic acidemia has been misdiagnosed as nonketotic hyperglycinemia (75).
Urinary organic acid analysis can be used to determine the type of organic acidemia or carboxylase deficiency. Elevated concentrations of propionate metabolites, such as beta-hydroxypropionate, methylcitrate, tiglic acid, and propionylglycine, in the absence of methylmalonic acid or isovaleric acid, suggest a diagnosis of propionic acidemia. The methylmalonic acidemias must be differentiated from propionic acidemia because some of the former are vitamin responsive. Elevated urinary concentrations of beta-hydroxyisovalerate, beta-methylcrotonylglycinuria, or lactate, in addition to methylcitrate and beta-hydroxypropionate, are indicative of multiple carboxylase deficiency.
Propionic acidemia can be differentiated from the multiple carboxylase deficiencies by direct assay of the carboxylases. Biotinidase deficiency can easily be excluded by direct enzymatic assay. Propionic acidemia can be confirmed by demonstrating deficient activity of propionyl-CoA carboxylase and normal activities of beta-methylcrotonyl-CoA and pyruvate carboxylase in peripheral blood leukocytes or in cultured fibroblasts (80; 208).
Several children were described with an infantile mitochondrial DNA depletion syndrome that is characterized by elevated urinary organic acids. Decreased activities of beta-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase were found in their fibroblasts. The depleted mtDNA is assumed to result in aberrations in normal mitochondrial function altering carboxylase activities (213).
Prenatal diagnosis of propionic acidemia is also possible by determining mutations in fetal DNA isolated from maternal blood (28).
Diagnostic workup
Elevated concentrations of propionate metabolites, such as beta-hydroxypropionate, methylcitrate, tiglic acid, and propionylglycine (in the absence of methylmalonic acid or isovaleric acid) on urinary organic acid analysis suggest a diagnosis of propionic acidemia. Propionate is elevated on organic acid analysis of plasma. The organic acids are usually still elevated even when the patient is metabolically stable. Propionic acidemia can also be diagnosed by finding elevated concentrations of propionylcarnitine in plasma or in blood-soaked filter paper spots (151). Propionic acidemia is definitively diagnosed by demonstrating deficient propionyl-CoA carboxylase activity and normal activities of beta-methylcrotonyl-CoA and pyruvate carboxylase in peripheral blood leukocytes, skin fibroblasts, or other tissues from suspected affected patients (79; 64; 80). Decreased incorporation of 14C-propionate into trichloroacetic acid-precipitable material in fibroblasts or leukocytes can be used to determine a defect in the propionate pathway, but it does not differentiate between propionyl-CoA carboxylase deficiency and the various methylmalonic acidemias (200).
Management
Management guidelines have been reported (60). Propionic acidemia must be treated rapidly and aggressively (205; 110). A consortium of clinical metabolic specialists reviewed the acute treatment of propionic acidemia (36). There have been guidelines presented for the general treatment of individuals with propionic acidemia (18) and for their acute illness (04). Affected individuals should be adequately hydrated, especially if there is evidence of dehydration. Large quantities of parenteral fluids help to facilitate excretion of abnormal organic acid metabolites. Adequate nutrition is essential (23). Acutely, protein is usually restricted because the branched-chain amino acids specifically are a source of organic acids, and the protein, in general, is a source of nitrogen for the hyperammonemia. Care must be taken to reintroduce protein with formulas that are restricted in isoleucine, threonine, methionine, and valine. However, intake of protein in excess of recommended quantities is likely to result in worse clinical outcomes (124). In addition, N-carbamoyl-L-glutamate, together with a protein-restricted diet and carnitine supplementation, may be effective in treating the hyperammonemia associated with propionic acidemia (169; 178; 189). Determinations of various metabolites in filter-paper blood and urinary samples can be used to more closely and more frequently follow the biochemical and clinical course of individuals with propionic acidemia (179).
If protein is restricted for too long a period, the child may still develop hyperammonemia from the degradation of endogenous protein. Because inadequate caloric intake can result in tissue breakdown and endogenous protein degradation, it is imperative to supply sufficient calories in the form of parenteral glucose or oral polysaccharides. Some patients have been treated with parenteral hyperalimentation or continuous insulin infusion (91). Care must be taken not to cause hyperosmolar feedings, particularly when an individual has gastrointestinal problems.
Severe acidosis may require bicarbonate supplementation in addition to hydration. Severe metabolic acidosis and hyperammonemia may require exchange transfusion, hemodialysis, or peritoneal dialysis (158; 81). Evidence supports that severe hyperammonemia can be successfully treated with sodium benzoate or phenylacetate, which conjugate amine-containing compounds, thereby facilitating their excretion (81). These compounds, however, may aggravate the acidosis. Use of an intestinal motility agent resulted in a significant and rapid decrease in blood ammonia and a rise in the ratio of free to total carnitine (147). Enhancement of gut motility may be useful in maintaining metabolic stability in these children.
Intervening infections must be diagnosed and treated aggressively. Mineral and electrolyte concentrations should be carefully monitored. Serious bacterial infections and disseminated intravascular coagulopathy must be excluded in the severely ill child with thrombocytopenia, neutropenia, or pancytopenia.
Although propionyl-CoA carboxylase is a biotin-dependent enzyme, pharmacological doses of biotin (10 mg per day) have not resulted in true vitamin-responsiveness or increased carboxylase activity (204). Several patients with vitamin-responsive propionic acidemia have been reported, but on further investigation none have been substantiated. Biotin supplementation may help to optimize residual enzyme activity in those with some carboxylase activity (203).
Carnitine (100 mg/kg per day) is useful in resupplying the body with carnitine that is excreted as acylcarnitines, especially during severe organic acidemic episodes (160; 34). Carnitine supplementation can decrease the size of the liver in those patients with hepatomegaly, probably by adequately mobilizing the storage of acyl-derivatives during secondary carnitine deficiency.
Carglumic acid supplementation together with standard treatments in individuals with propionic acidemia have resulted in a decreased number of visits to the emergency department for hyperammonemia (07).
One report indicated that coQ10 was decreased in metabolically compromised individuals with propionic acidemia that was likely due to mitochondrial dysfunction (180). Ubiquinol supplementation increased the urinary excretion of citrate and the citrate/methylcitrate ratio in these individuals, indicative of improved anaplerosis. The authors suggested further studies are necessary to confirm these results.
Three children with propionic acidemia who were treated with growth hormone (two had decreased hormone secretion) exhibited increased linear growth. Protein tolerance was also increased during hormone treatment. Growth hormone therapy may be useful in the treatment of children with propionic acidemia, particularly those with growth retardation (118).
Several children with propionic acidemia who had frequent and severe metabolic compromise have undergone orthotopic liver transplantation at 7 to 9 years of age (167; 95). The results have been equivocal even when the children were maintained on a protein-restricted diet supplemented with biotin and carnitine. However, in another study, a child was transplanted with a living-related liver (216). The metabolic abnormalities corrected, and the child tolerated a protein diet up to 2 g/kg per day. In addition, the child’s growth and development improved. Living donor liver transplantation or partial liver grafts from asymptomatic obligate heterozygous (parental) donors in propionic acidemia is being performed successfully (217). Preliminary results indicate that although there is a high survival rate, pretransplant growth retardation adversely affects posttransplant outcomes (126; 166). A review of 12 children who have undergone liver transplantation revealed clinical improvement, including cessation of decline in neurologic and cognitive function, in some even to the point of reducing or discontinuing the need for protein restriction or other medical treatments (15). The study suggested that transplantation should be considered in those children who continued to experience severe metabolic compromise in spite of maximal medical intervention (46). Moreover, transplantation may limit the degree of developmental delay and cardiomyopathy (161; 14). Two centers have reported the early and late complications of liver transplantation in propionic acidemia (37). There has been a cost-effectiveness analysis of liver transplantation for propionic acidemia (112). Additional experience and careful follow-up, especially when performed before major neurologic irreversible effects, have occurred. Favorable long-term outcomes of auxiliary liver transplantation in this disorder are being reported (153; 192; 130; 14; 83; 42; 146; 06; 47; 214; 218). It is important to follow these individuals diligently long-term because they can rapidly become compromised or develop strokes (176). Transplantation in propionic academia has a high risk of complications and requires highly specialized preoperative and perioperative management, involving a multidisciplinary team (33).
A mouse with propionyl-CoA carboxylase deficiency, which causes death soon after birth, was successfully treated with a liver-specific carboxylase delivered transgenically after birth (122). An adeno-associated virus gene transfer successfully rescued a neonatal lethal mouse with propionic acidemia (35).
During periods of metabolic stability, therapy consists of restricting the dietary intake of the various branched-chain amino acids that are not metabolized in this disorder. During infancy this is accomplished by using artificial commercial formulas. These formulas are usually supplemented with normal formulas and should be adjusted on a regular basis by a dietitian trained in metabolic disorders. Dietary restriction is lifelong, with an increasing dependency on using natural foods. For enzyme-deficient children, the diet is usually supplemented with carnitine and biotin. There should be routine consultations with metabolic specialists and dietitians as well as periodic developmental assessments and psychosocial support of the patient and family. Studies have suggested that citrate may be an anaplerotic therapy for individuals with propionic acidemia by increasing the downstream concentrations of intermediates in the Krebs cycle (114). A study determined that parents of individuals with propionic acidemia often make adjustments in their child’s diet (109). These alterations may not correspond to the recommendations of the metabolic team, and the parents may not inform the team about the changes made in the diet.
Because one of the long-term complications of organic acidemias is impaired mitochondrial metabolism, elevations of the biomarker, fibroblast growth factor 21 (FGF-21), were found in individuals with metabolic compromise compared to that in individuals with stable metabolic disease (125).
The Inborn Errors of Metabolism Collaborative found that newborn screening identified individuals with propionic acidemia earlier than those who presented with symptoms (121). There was no correlation between the genotype and C3 acylcarnitine concentrations. Further studies are needed to evaluate the long-term outcomes based on the mode of ascertainment.
Outcomes
The outcomes of individuals with propionic acidemia has been variable, with many exhibiting complications, such as cardiac arrhythmias (72; 73). Systematic collaborations and follow-up is necessary for developing better management guidelines for individuals with propionic acidemia at all ages (18). As described above, more individuals with propionic acidemia are being treated with liver transplantation. Systematic evaluation of outcomes of this intervention is essential to determine its efficacy (47; 214).
Special considerations
Pregnancy
One pregnant woman with mild propionic acidemia who was maintained on a protein-restricted diet and carnitine supplementation delivered a healthy child (191).
Anesthesia
Surgeons and anesthesiologists must have a though understanding of the volatility of this disorder before and during surgery, particularly liver transplantation (149). There has been a report of peripheral nerve block in an individual with the disorder (177).
Media
References
- 01
- Akman I, Imamoglu S, Demirkol M, Alpay H, Ozek E. Neonatal onset propionic acidemia without acidosis: a case report. Turk J Pediatr 2002;44:339-42. PMID 12458812
- 02
- Alberola TM, Bautista-Llácer R, Vendrell X, et al. Case report: birth of healthy twins after preimplantation genetic diagnosis of propionic acidemia. J Assist Reprod Genet 2011;28(3):211-6. PMID 21125326
- 03
- Al-Dirbashi OY, McIntosh N, McRoberts C, et al. Analysis of methylcitrate in dried blood spots by liquid chromatography-tandem mass spectrometry. JIMD Rep 2014;16:65-73. PMID 24997714
- 04
- Aldubayan SH, Rodan LH, Berry GT, Levy HL. Acute illness protocol for organic acidemias: methylmalonic acidemia and propionic acidemia. Pediatr Emerg Care 2017;33(2):142-6. PMID 28141776
- 05
- Al-Essa M, Bakheet S, Patay Z, et al. 18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in propionic acidemia: clinical and MRI correlations. Brain Dev 1999;21:312-7. PMID 10413018
- 06
- Alexopoulos SP, Matsuoka L, Hafberg E, et al. Liver transplantation for propionic acidemia: a multi-center linked database analysis. J Pediatr Gastroenterol Nutr 2020;70(2):178-82. PMID 31633652
- 07
- Alfadhel M, Nashabat M, Saleh M, et al. Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): a randomized clinical trial. Orphanet J Rare Dis 2021;16:422. PMID 34635114
- 08
- Al-Hamed MH, Imtiaz F, Al-Hassnan Z, et al. Spectrum of mutations underlying Propionic acidemia and further insight into a genotype-phenotype correlation for the common mutation in Saudi Arabia. Mol Genet Metab Rep 2019;18:22-9. PMID 30705822
- 09
- Almuqbil M, Chinsky JM, Srivastava S. Metabolic strokes in propionic acidemia: transient hemiplegic events without encephalopathy. Child Neurol Open 2019. PMID 31523698
- 10
- Al-Owain M, Kaya N, Al-Shamrani H, et al. Autism spectrum disorder in a child with propionic acidemia. J Inherit Metab Dis Rep 2013;7:63-6. PMID 23430497
- 11
- Ando T, Nyhan WL, Gerritsen T, Gong L, Heiner DC, Bray PF. Metabolism of glycine in the nonketotic form of hyperglycinemia. Pediatr Res 1968;2:254-63. PMID 5669662
- 12
- Ando T, Rasmussen K, Nyhan WL, Donnell GN, Barnes ND. Propionic acidemia in patients with ketotic hyperglycinemia. J Pediatr 1971;78:827-32. PMID 5581587
- 13
- Arias C, Raimann E, Peredo P, et al. Propionic acidemia and optic neuropathy: a report of two cases. J Inherit Metab Dis Rep 2014;12:1-4. PMID 23818179
- 14
- Arrizza C, De Gottardi A, Foglia E, Baumgartner M, Gautschi M, Nuoffer JM. Reversal of cardiomyopathy in propionic acidemia after liver transplantation: a 10-year follow-up. Transpl Int 2015;28(12):1447-50. PMID 26358860
- 15
- Barshes NR, Vanatta JM, Patel AJ, et al. Evaluation and management of patients with propionic acidemia undergoing liver transplantation: a comprehensive review. Pediatr Transplant 2006;10(7):773-81. PMID 17032422
- 16
- Baruteau J, Hargreaves I, Krywawych S, et al. Successful reversal of propionic acidaemia associated cardiomyopathy: evidence for low myocardial coenzyme Q10 status and secondary mitochondrial dysfunction as an underlying pathophysiological mechanism. Mitochondrion 2014;17:150-6. PMID 25010387
- 17
- Baumgartner D, Scholl-Burgi S, Sass JO, et al. Prolonged QTc intervals and decreased left ventricular contractility in patients with propionic acidemia. J Pediatr 2007;150(2):192-7. PMID 17236900
- 18
- Baumgartner MR, Hörster F, Dionisi-Vici C, et al. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis 2014;9:130. PMID 25205257
- 19
- Behbehani AW, Lehnert W, Langenbeck U, Luthe H, Baumgartner R. Propionic acidemia with myelination of the CNS. Klin Padiatr 1984;196:106-10. PMID 6737946
- 20
- Bergman AJ, Van der Knaap MS, Smeitink JA, et al. Magnetic resonance imaging and spectroscopy of the brain in propionic acidemia: clinical and biochemical considerations. Pediatr Res 1996;40:404-9. PMID 8865276
- 21
- Bernheim S, Deschênes G, Schiff M, Cussenot I, Niel O. Antenatal nephromegaly and propionic acidemia: a case report. BMC Nephrol 2017;18(1):110. PMID 28359305
- 22
- Bodi I, Grünert SC, Becker N, et al. Mechanisms of acquired long QT syndrome in patients with propionic academia. Heart Rhythm 2016;13(6):1335-45. PMID 26854997
- 23
- Brandt IK, Hsia YE, Clement DH, Provence SA. Propionicacidemia (ketotic hyperglycinemia) dietary treatment resulting in normal growth and development. Pediatrics 1974;53:391-5. PMID 4815259
- 24
- Brismar J, Ozand PT. CT and MR of the brain in disorders of the propionate and methylmalonate metabolism. AJNR Am J Neuroradiol 1994;15:1459-73. PMID 7985563
- 25
- Broomfield A, Gunny R, Prabhakar P, Grunewald S. Spontaneous rapid resolution of acute basal ganglia changes in an untreated infant with propionic acidemia: a clue to pathogenesis. Neuropediatrics 2010;41(6):256-60. PMID 21445815
- 26
- Brosch S, Rauffeisen A, Baur M, Michels L, Trefz FK, Pfister M. Propionic acidemia and sensorineural hearing loss: is there a connection at the molecular genetics level. HNO 2008;56(1):37-42. PMID 17415538
- 27
- Bultron G, Seashore MR, Pashankar DS, Husain SZ. Recurrent acute pancreatitis associated with propionic acidemia. J Pediatr Gastroenterol Nutr 2008;47(3):370-1. PMID 18728537
- 28
- Bustamante-Aragones A, Perez-Cerda C, Perez B, de Alba MR, Ugarte M, Ramos C. Prenatal diagnosis in maternal plasma of a fetal mutation causing propionic acidemia. Mol Genet Metab 2008;95(1-2):101-3. PMID 18599334
- 29
- Campeau E, Desviat LR, Leclerc D, et al. Structure of the PCCA gene and distribution of mutations causing propionic acidemia. Mol Genet Metab 2001;74:238-47. PMID 11592820
- 30
- Campeau E, Dupuis L, Leclerc D, Gravel RA. Detection of a normally rare transcript in propionic acidemia patients with mRNA destabilizing mutations in the PCCA gene. Hum Mol Genet 1999a;8:107-13. PMID 9887338
- 31
- Campeau E, Dupuis L, Leon-Del-Rio A, Gravel R. Coding sequence mutations in the alpha subunit of propionyl-CoA carboxylase in patients with propionic acidemia. Mol Genet Metab 1999b;67:11-22. PMID 10329019
- 32
- Chadefaux B, Augereau C, Rabier D, et al. Prenatal diagnosis of propionic acidemia in chorionic villi by direct assay of propionyl CoA carboxylase. Prenat Diagn 1988;8:161-4. PMID 3362779
- 33
- Chakrapani A, Stojanovic J, Vara R, De Nictolis F, Spada M, Dionisi-Vici C. Safety, efficacy, and timing of transplantation(s) in propionic and methylmalonic aciduria. J Inherit Metab Dis 2023;46(3):466-81. PMID 37067856
- 34
- Chalmers RA, Roe CR, Stacey TE, Hoppel CL. Urinary excretion of L-carnitine and acylcarnitines by patients with disorders of organic acid metabolism: evidence for secondary insufficiency of L-carnitine. Pediatr Res 1984;18:1325-8. PMID 6441143
- 35
- Chandler RJ, Chandrasekaran S, Carrillo-Carrasco N, et al. Adeno-associated virus serotype 8 gene transfer rescues a neonatal lethal murine model of propionic acidemia. Hum Gene Ther 2011;22(4):477-81. PMID 20950151
- 36
- Chapman KA, Gropman A, MacLeod E, et al. Acute management of propionic acidemia. Mol Genet Metab 2012;105:16-25. PMID 22000903
- 37
- Charbit-Henrion F, Lacaille F, McKiernan P, et al. Early and late complications after liver transplantation for propionic acidemia in children: a two centers study. Am J Transplant 2015;15(3):786-91. PMID 25683683
- 38
- Chemelli AP, Schocke M, Sperl W, Trieb T, Aichner F, Felber S. Magnetic resonance spectroscopy (MRS) in five patients with treated propionic acidemia. J Magn Reson Imaging 2000;11:596-600. PMID 10862057
- 39
- Chen Z, Wen P, Wang G, Hu Y, Liu X, Chen L, Chen S, Wan L, Cui D, Shang Y, Li C. Analysis of PCCA and PCCB gene mutations in patients with propionic acidemia. [Article in Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2015;32:26-30. PMID 25636094
- 40
- Childs B, Nyhan WL, Borden MA, Bard L, Cooke RE. Idiopathic hyperglycinemia and hyperglycinuria, a new disorder of amino acid metabolism. Pediatrics 1961;27:522-38. PMID 13693094
- 41
- Chloupkova M, Maclean KN, Alkhateeb A, Kraus JP. Propionic acidemia: analysis of mutant propionyl-CoA carboxylase enzymes expressed in Escherichia coli. Hum Mutat 2002;19:629-40. PMID 12007220
- 42
- Chu TH, Chien YH, Lin HY, et al. Methylmalonic acidemia/propionic acidemia - the biochemical presentation and comparing the outcome between liver transplantation versus non-liver transplantation groups. Orphanet J Rare Dis 2019;14(1):73. PMID 30940196
- 43
- Clavero S, Martinez MA, Perez B, Perez-Cerda C, Ugarte M, Desviat LR. Functional characterization of PCCA mutations causing propionic acidemia. Biochim Biophys Acta 2002;1588:119-25. PMID 12385775
- 44
- Clavero S, Perez B, Rincon A, Ugarte M, Desviat LR. Qualitative and quantitative analysis of the effect of splicing mutations in propionic acidemia underlying non-severe phenotypes. Hum Genet 2004;115:239-47. PMID 15235904
- 45
- Coude FX, Sweetman L, Nyhan WL. Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat liver mitochondria: a possible explanation for hyperammonemia in propionic and methylmalonic acidemia. J Clin Invest 1979;64:1544-51. PMID 500823
- 46
- Critelli K, McKiernan P, Vockley J, et al. Liver transplantation for propionic acidemia and methylmalonic acidemia: perioperative management and clinical outcomes. Liver Transpl 2018;24(9):1260-70. PMID 30080956
- 47
- Curnock R, Heaton ND, Vilca-Melendez,H, Dhawan A, Hadzic N, Vara R. Liver transplantation in children with propionic acidemia: Medium-term outcomes. Liver Transpl. 2020;26(3):419-30. PMID 31715057
- 48
- Dejean de la Bâtie C, Barbier V, Valayannopoulos V, et al. Acute psychosis in propionic acidemia: 2 case reports. J Child Neurol 2014;29(2):274-9. PMID 24334345
- 49
- de la Batie CD, Barbier V, Roda C, et al. Autism spectrum disorders in propionic acidemia patients. J Inherit Metab Dis 2018;41(4):623-9. PMID 28856627
- 50
- Della Rossa AA, Dixit PM, Shah R, Hang S, Duong J. Ventricular arrhythmias in a patient with propionic acidemia. Cureus 2022;14(9):e28966. PMID 36111330
- 51
- De Raeve L, De Meirleir L, Ramet J, Vandenplas Y, Gerlo E. Acrodermatitis enteropathica-like cutaneous lesions in organic aciduria. J Pediatr 1994;124:416-20. PMID 8120711
- 52
- Desviat LR, Clavero S, Perez-Cerda C, Navarrete R, Ugarte M, Perez B. New splicing mutations in propionic acidemia. J Hum Genet 2006;51(11):992-7. PMID 17051315
- 53
- Desviat LR, Perez B, Perez-Cerda C, Rodriguez-Pombo P, Clavero S, Ugarte M. Propionic acidemia: mutation update and functional and structural effects of the variant alleles. Mol Genet Metab 2004;83(1-2):28-37. PMID 15464417
- 54
- Desviat LR, Sanchez-Alcudia R, Pérez B, et al. High frequency of large genomic deletions in the PCCA gene causing propionic acidemia. Mol Genet Metab 2009;96(4):171-6. PMID 19157943
- 55
- Dhondt JL, Farriaux JP, Amedee Manesme O, Cartigny B. Antenatal diagnosis of propionic acidemia by methylcitrate determination. J Inherit Metab Dis 1981;4:49-50. PMID 6790842
- 56
- Duras E, İrdem A, Özkaya O. Long QT syndrome diagnosed in two sisters with propionic acidemia: a case report. J Pediatr Endocrinol Metab 2017;30(10):1133-6. PMID 28820736
- 57
- Dweikat IM, Naser EN, Abu Libdeh AI, et al. Propionic acidemia mimicking diabetic ketoacidosis. Brain Dev 2011;33(5):428-31. PMID 20634010
- 58
- Ehrenberg S, Walsh Vockley C, Heiman P, et al. Natural history of propionic acidemia in the Amish population. Mol Genet Metab Rep 2022;33:100936. PMID 36393899
- 59
- Fragaki K, Cano A, Benoist JF, et al. Fatal heart failure associated with CoQ10 and multiple OXPHOS deficiency in a child with propionic acidemia. Mitochondrion 2011;11(3):533-6. PMID 21329767
- 60
- Fraser JL, Venditti CP. Methylmalonic and propionic acidemias: clinical management update. Curr Opin Pediatr 2016;28(6):682-93. PMID 27653704
- 61
- Gascon GG, Ozand PT, Brismar J. Movement disorders in childhood organic acidurias. Clinical, neuroimaging, and biochemical correlations. Brain Dev 1994;16:94-103. PMID 7726387
- 62
- Gebarski SS, Gabrielsen TO, Knake JE, Latack JT. Cerebral CT findings in methylmalonic acid and propionic acidemias. AJNR Am J Neuroradiol 1983;4:955-7. PMID 6410881
- 63
- Gompertz D, Goodeye PA, Thom H, et al. Prenatal diagnosis and family studies in a case of propionicacidemia. Clin Genet 1975;8:244-50. PMID 1183068
- 64
- Gompertz D, Storres CN, Bau DC, Peters TJ, Hughes EA. Localization of enzymatic defect in propionic-acidemia. Lancet 1970;1:1140-3. PMID 4192098
- 65
- Gravel RA, Lam KF, Scully KJ, Hsia YE. Genetic complementation of propionyl-CoA carboxylase deficiency in cultured human fibroblasts. Am J Hum Genet 1977;29:378-88. PMID 195466
- 66
- Grünert SC, Bodi I, Odening KE. Possible mechanisms for sensorineural hearing loss and deafness in patients with propionic acidemia. Orphanet J Rare Dis 2017;12(1):30. PMID 28193246
- 67
- Grünert SC, Müllerleile S, de Silva L, et al. Propionic acidemia: neonatal versus selective metabolic screening. J Inherit Metab Dis 2012;35:41-9. PMID 22134541
- 68
- Grünert SC, Müllerleile S, De Silva L, et al. Propionic acidemia: clinical course and outcome in 55 pediatric and adolescent patients. Orphanet J Rare Dis 2013;8:6. PMID 23305374
- 69
- Gupta D, Bijarnia-Mahay S, Kohli S, et al. Seventeen novel mutations in PCCA and PCCB genes in Indian propionic acidemia patients, and their outcomes. Genet Test Mol Biomarkers 2016;20(7):373-82. PMID 27227689
- 70
- Haas RH, Marsden DL, Capistrano-Estrada S, et al. Acute basal ganglia infarction in propionic acidemia. J Child Neurol 1995;10:18-22. PMID 7769171
- 71
- Haberlandt E, Canestrini C, Brunner-Krainz M, et al. Epilepsy in patients with propionic acidemia. Neuropediatrics 2009;40(3):120-5. PMID 20020396
- 72
- Haijes HA, Jans JJM, Tas SY, Verhoeven-Duif NM, van Hasselt PM. Pathophysiology of propionic and methylmalonic acidemias. Part 1: Complications. J Inherit Metab Dis 2019a;42(5):730-44. PMID 31119747
- 73
- Haijes HA, van Hasselt PM, Jans JJM, Verhoeven-Duif NM. Pathophysiology of propionic and methylmalonic acidemias. Part 2: Treatment strategies. J Inherit Metab Dis 2019b;42(5):730-44. PMID 31119742
- 74
- Hamilton RL, Haas RH, Nyhan WL, Powell HC, Grafe MR. Neuropathology of propionic acidemia: a report of two patients with basal ganglia lesions. J Child Neurol 1995;10:25-30. PMID 7769173
- 75
- Harris DJ, Yang BI, Thompson RM, Wolf B. Propionyl CoA carboxylase deficiency presenting as non-ketotic hyperglycinemia. J Med Genet 1981;18:156-7. PMID 7241536
- 76
- Harris DJ, Yang BI, Wolf B, Snodgrass PJ. Dysautonomia in an infant with secondary hyperammonemia due to propionyl coenzyme A carboxylase deficiency. Pediatrics 1980;65:107-10. PMID 7355003
- 77
- Henriquez H, el Din A, Ozand PT, Subramanyam SB, al Gain SI. Emergency presentations of patients with methylmalonic acidemia, propionic acidemia and branched chain amino acidemia (MSUD). Brain Dev 1994;16:86-93. PMID 7726386
- 78
- Hommes FA, Kuipers JR, Elema JD, Jansen JF, Jonix JH. Propionicacidemia, a new inborn error of metabolism. Pediatr Res 1968;2:519-24. PMID 5727920
- 79
- Hsia YE, Scully KJ, Rosenberg LE. Defective propionate carboxylation in ketotic hyperglycinemia. Lancet 1969;1(7598):757-8. PMID 4180220
- 80
- Hsia YE, Scully KJ, Rosenberg LE. Inherited propionyl CoA carboxylase deficiency in "ketotic hyperglycinemia." J Clin Invest 1971;50:127-30. PMID 5101292
- 81
- Hsu WC, Lin SP, Huang FY, Wang PA, Hsiao KJ. Propionic acidemia: report of a case that is successfully managed by peritoneal dialysis and sodium benzoate therapy. Chung Hua I Hsueh Tsa Chih 1990;46:306-10. PMID 2178070
- 82
- Ianchulev T, Kolin T, Moseley K, Sadun A. Optic nerve atrophy in propionic acidemia. Ophthalmology 2003;110:1850-4. PMID 13129889
- 83
- Imbard A, Garcia Segarra N, Tardieu M, et al. Long-term liver disease in methylmalonic and propionic acidemias. Mol Genet Metab 2018;123(4):433-40. PMID 29433791
- 84
- Inoue Y, Kuhara T. Rapid and sensitive method for prenatal diagnosis of propionic acidemia using stable isotope dilution gas chromatography-mass spectrometry and urease pretreatment. J Chromatogr B Analyt Technol Biomed Life Sci 2002;776:71-7. PMID 12127327
- 85
- Iwashima S, Ishikawa T, Ohzeki T, Endou Y. Delayed enhancement cardiac magnetic resonance imaging in propionic acidemia. Pediatr Cardiol 2010;31(6):884-6. PMID 20490478
- 86
- Jakobs C, Sweetman L, Nyhan WL. Stable isotope dilution analysis of 3-hydroxyisovaleric acid in amniotic fluid: contribution to the prenatal diagnosis of inherited disorders of leucine catabolism. J Inherit Metab Dis 1984;7:15-20. PMID 6429435
- 87
- Jameson E, Walter J. Cardiac arrest secondary to long QT(C) in a child with propionic acidemia. Pediatr Cardiol 2007;29(5):969-70. PMID 18058159
- 88
- Jiang H, Rao KS, Yee VC, Kraus JP. Characterization of four variant forms of human propionyl-CoA carboxylase expressed in Escherichia coli. J Biol Chem 2005;280(30):27719-27. PMID 15890657
- 89
- Kakavand B, Schroeder VA, Di Sessa TG. Coincidence of long QT syndrome and propionic acidemia. Pediatr Cardiol 2006;27(1):160-1. PMID 16391987
- 90
- Kalidas K, Behrouz R. Inherited metabolic disorders and cerebral infarction. Expert Rev Neurother 2008;8(11):1731-41. PMID 18986243
- 91
- Kalloghlian A, Gleispach H, Ozand PT. A patient with propionic acidemia managed with continuous insulin infusion and total parenteral nutrition. J Child Neurol 1992;7:S88-91. PMID 1588020
- 92
- Karimzadeh P, Jafari N, Ahmad Abadi F, et al. Propionic acidemia: diagnosis and neuroimaging findings of this neurometabolic disorder. Iran J Child Neurol 2014;8:58-61. PMID 24665329
- 93
- Kasapkara CS, Akar M, Yürük Yıldırım ZN, Tüzün H, Kanar B, Ozbek MN. Severe renal failure and hyperammonemia in a newborn with propionic acidemia: effects of treatment on the clinical course. Ren Fail 2014;36(3):451-2. PMID 24329397
- 94
- Kaya N, Al-Owain M, Albakheet A, et al. Array comparative genomic hybridization (aCGH) reveals the largest novel deletion in PCCA found in a Saudi family with propionic acidemia. Eur J Med Genet 2008;51(6):558-65. PMID 18790721
- 95
- Kayler LK, Merion RM, Lee S, et al. Long-term survival after liver transplantation in children with metabolic disorders. Pediatr Transplant 2002;6:295-300. PMID 12234269
- 96
- Kennerknecht I, Sourmala T, Barbi G, Baumgartner ER. The gene coding for the alpha-subunit of human propionyl-CoA carboxylase maps to chromosome band 13q32. Hum Genet 1990;86:238-40. PMID 2265838
- 97
- Kido J, Matsumoto S, Sawada T, Endo F, Nakamura K. Rhabdomyolysis in organic acidemia patients manifesting with metabolic decompensation. Hemodial Int 2019;23(4):E115-9. PMID 31476111
- 98
- Kim SN, Ryu KH, Lee EH, Kim JS, Hahn SH. Molecular analysis of PCCB gene in Korean patients with propionic acidemia. Mol Genet Metab 2002;77:209-16. PMID 12409268
- 99
- Koker SA, Yesibbas O, Koker A, Sevketoglu. Propionic acidemia: An extremely rare cause of hemophagocytic lymphohistiocytosis in an infant. Arch Argent Pediatr 2020;118(2):e174-7. PMID 32199059
- 100
- Kovacevic A, Garbade SF, Hoffmann GF, Gorenflo M, Kolker S, Staufner C. Cardiac phenotype in propionic acidemia-Results of an observational monocentric study. Mol Genet Metab 2020;130(1):41-8. PMID 32067920
- 101
- Kraus JP, Spector E, Venezia S, et al. Mutation analysis in 54 propionic acidemia patients. J Inherit Metab Dis 2012;35:51-63. PMID 22033733
- 102
- Kraus JP, Williamson CL, Firgiaira FA, et al. Cloning nanogram amounts of immunopurified mRNAs: cDNA cloning and chromosomal mapping of cystathionine synthetase and the beta subunit of propionyl CoA carboxylase. Proc Natl Acad Sci U S A 1986;83:2047-51. PMID 3457373
- 103
- Kurolap A, Barel D, Shaul Lotan N, et al. A common benign intronic deletion masking a pathogenic deep intronic PCCB variant - genome sequencing and RNA studies to the rescue. Mol Genet Metab 2023;140(3):107702. PMID 37776842
- 104
- la Marca G, Malvagia S, Pasquini E, Innocenti M, Donati MA, Zammarchi E. Rapid 2nd-tier test for measurement of 3-OH-propionic and methylmalonic acids on dried blood spots: reducing the false-positive rate for propionylcarnitine during expanded newborn screening by liquid chromatography-tandem mass spectrometry. Clin Chem 2007;53(7):1364-9. PMID 17510301
- 105
- Laemmle A, Balmer C, Doell C, Sass JO, Häberle J, Baumgartner MR. Propionic acidemia in a previously healthy adolescent with acute onset of dilated cardiomyopathy. Eur J Pediatr 2014;173:971-4. PMID 24916042
- 106
- Lam Hon Wah AM, Lam KF, Tsui F, et al. Assignment of the alpha and beta chains of propionyl-CoA carboxylase to the genetic complementation groups. Am J Hum Genet 1983;35:889-99. PMID 6614005
- 107
- Lamhonwah AM, Barankiewicz TJ, Willard HF. Isolation of cDNA clones coding for the alpha and beta chains of human propionyl-CoA carboxylase: chromosomal assignments and DNA polymorphisms associated with PCCA and PCCB genes. Proc Natl Acad Sci U S A 1986;83:4864-8. PMID 3460076
- 108
- Lamhonwah AM, Troxel CE, Schuster S, Gravel RA. Two distinct mutations at the same site in the PCCB gene in propionic acidemia. Genomics 1990;8:249-54. PMID 2249848
- 109
- Lea D, Shchelochkov O, Cleary J, Koehly LM. Dietary management of propionic acidemia: parent caregiver perspectives and practices. JPEN J Parenter Enteral Nutr 2019;43(3):434-7. PMID 30357861
- 110
- Leonard JV, Daish P, Naughten ER, Bartlett K. The management and long term outcome of organic acidaemias. J Inherit Metab Dis 1984;7:13-7. PMID 6434837
- 111
- Levy HL. Newborn screening for metabolic disorders. N Engl J Med 1973;288:1299-300. PMID 4703321
- 112
- Li M, Dick A, Montenovo M, Horslen S, Hansen R. Cost-effectiveness of liver transplantation in methylmalonic and propionic acidemias. Liver Transpl 2015;21(9):1208-18. PMID 25990417
- 113
- Liu Y, Chen Z, Dong H, et al. Analysis of the relationship between phenotypes and genotypes in 60 Chinese patients with propionic acidemia: a fourteen-year experience at a tertiary hospital. Orphanet J Rare Dis 2022;17(1):135. PMID 35331292
- 114
- Longo N, Price LB, Gappmaier E, et al. Anaplerotic therapy in propionic acidemia. Mol Genet Metab 2017;122(1-2):51-9. PMID 28712602
- 115
- Lucke T, Perez-Cerda C, Baumgartner M, et al. Propionic acidemia: unusual course with late onset and fatal outcome. Metabolism 2004;53(6):809-10. PMID 15164333
- 116
- Ma X, Liu Y, Chen ZH, et al. Phenotypes and genotypes of 78 patients with propionic acidemia. Zhonghua Yu Fang Yi Xue Za Zhi 2022;56(9):1263-71. PMID 36207890
- 117
- Mardach R, Verity MA, Cederbaum SD. Clinical, pathological, and biochemical studies in a patient with propionic acidemia and fatal cardiomyopathy. Mol Genet Metab 2005;85:286-90. PMID 15939644
- 118
- Marsden D, Barshop BA, Capistrano-Estrada S, et al. Anabolic effect of human growth hormone: management of inherited disorders of catabolic pathways. Biochem Med Metab Biol 1994;52:145-54. PMID 7993663
- 119
- Martinez Alvarez L, Jameson E, Parry NR, Lloyd C, Ashworth JL. Optic neuropathy in methylmalonic acidemia and propionic acidemia. Br J Ophthalmol 2016;100(1):98-104. PMID 26209586
- 120
- Massoud AF, Leonard JV. Cardiomyopathy in propionic acidemia. Eur J Pediatr 1993;152:441-5. PMID 8319715
- 121
- McCrory NM, Edick MJ, Ahmad A, et al. Comparison of methods of initial ascertainment in 58 cases of propionic acidemia enrolled in the inborn errors of metabolism information system reveals significant differences in time to evaluation and symptoms at presentation. J Pediatr 2017;180:200-5. PMID 27776753
- 122
- Miyazaki T, Ohura T, Kobayashi M, et al. Fatal propionic acidemia in mice lacking propionyl-CoA carboxylase and its rescue by postnatal, liver-specific supplementation via a transgene. J Biol Chem 2001;216:35995-9. PMID 11461925
- 123
- Molema F, Gleich F, Burgard P, et al. Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: options for treatment. Mol Genet Metab 2019;126(4):397-405. PMID 30827756
- 124
- Molema F, Haijes HA, Janssen MC, et al. High protein prescription in methylmalonic and propionic acidemia patients and its negative association with long-term outcome. Clin Nutr 2021;40:3622-30. PMID 33451859
- 125
- Molema F, Jacobs EH, Onkenhout W, Schoonderwoerd GC, Langendonk JG, Williams M. Fibroblast growth factor 21 as a biomarker for long-term complications in organic acidemias. J Inherit Metab Dis 2018;41(6):1179-87. PMID 30159853
- 126
- Morioka D, Kasahara M, Takada Y, et al. Living donor liver transplantation for pediatric patients with inheritable metabolic disorders. Am J Transplant 2005;5(11):2754-63. PMID 16212637
- 127
- Muller S, Falkenberg N, Monch E, Jakobs C. Propionic acidaemia and immunodeficiency. Lancet 1980;1:551-2. PMID 6102279
- 128
- Muro S, Perez B, Desviat LR, et al. Effect of PCCB gene mutations on the heteromeric and homomeric assembly of propionyl-CoA carboxylase. Mol Genet Metab 2001;74:476-83. PMID 11749052
- 129
- Muro S, Rodriguez-Pombo P, Perez B, et al. Identification of novel mutations in the PCCB gene in European propionic acidemia patients. Mutation in brief no. 253. Online. Hum Mutat 1999;14:89-90. PMID 10447268
- 130
- Nagao M, Tanaka T, Morii M, Wakai S, Horikawa R, Kasahara M. Improved neurologic prognosis for a patient with propionic acidemia who received early living donor liver transplantation. Mol Genet Metab 2013;108(1):25-9. PMID 23151386
- 131
- Naylor G, Sweetman L, Nyhan WL, et al. Isotope dilution analysis of methylcitric acid in amniotic fluid for the prenatal diagnosis of propionic and methylmalonic acidemia. Clin Chim Acta 1980;107:175-83. PMID 7002368
- 132
- North KN, Korson MS, Gopal YR, et al. Neonatal-onset propionic acidemia: neurologic and developmental profiles, and implications for management. J Pediatr 1995;126:916-22. PMID 7539836
- 133
- Nyhan WL, Bay C, Beyer EW, Mazi M. Neurologic nonmetabolic presentation of propionic acidemia. Arch Neurol 1999;56:1143-7. PMID 10488817
- 134
- Nyhan WL, Borden M, Childs B. Idiopathic hyperglycinemia, a new disorder of amino acid metabolism. Pediatrics 1961;27:539-50. PMID 13729969
- 135
- Ohura T, Kraus JP, Rosenberg LE. Unequal synthesis and differential degradation of propionyl-CoA carboxylase subunits in cells from normal and propionic acidemic patients. Am J Hum Genet 1989;45:33-40. PMID 2741949
- 136
- Ohura T, Miyabayashi S, Narisawa K, Taka K. Genetic heterogeneity of propionic acidemia: analysis of 15 Japanese patients. Hum Genet 1991;87:41-4. PMID 2037281
- 137
- Ohura T, Narisawa K, Tada K, Iinuma K. A novel splicing mutation in propionic acidemia associated with a tetranucleotide direct repeat in the PCCB gene. Hum Genet 1995;95:707-8. PMID 7789958
- 138
- Ohura T, Ogasawara M, Ikeda H, Narisawa K, Tada K. The molecular defect in propionic acidemia: exon skipping caused by an 8-bp deletion from an intron in the PCCB allele. Hum Genet 1993;92:397-402. PMID 8225321
- 139
- Ozand PT, Rashed M, Gascon GG, et al. Unusual presentations of propionic acidemia. Brain Dev 1994;16:46-57. PMID 7726381
- 140
- Pena L, Franks J, Chapman KA, et al. Natural history of propionic acidemia. Mol Genet Metab 2012;105:5-9. PMID 21986446
- 141
- Perez B, Desviat LR, Rodriguez-Pombo P, et al. Propionic acidemia: identification of twenty-four novel mutations in Europe and North America. Mol Genet Metab 2003;78:59-67. PMID 12559849
- 142
- Perez-Cerda C, Clavero S, Perez B, Rodriguez-Pombo P, Desviat LR, Ugarte M. Functional analysis of PCCB mutations causing propionic acidemia based on expression studies in deficient human skin fibroblasts. Biochim Biophys Acta 2003;1638:43-9. PMID 12757933
- 143
- Perez-Cerda C, Merinero B, Marti M, et al. An unusual late-onset case of propionic acidaemia: biochemical investigations, neuroradiological findings and mutation analysis. Eur J Pediatr 1998;157:50-2. PMID 9461363
- 144
- Perez-Cerda C, Merinero B, Rodriguez-Pombo P, et al. Potential relationship between genotype and clinical outcome in propionic acidaemia patients. Eur J Hum Genet 2000;8:187-94. PMID 10780784
- 145
- Perez-Cerda C, Perez B, Merinero B, Desviat LR, Rodriguez-Pombo P, Ugarte M. Prenatal diagnosis of propionic acidemia. Prenat Diagn 2004;24:962-4. PMID 15614906
- 146
- Pillai NR, Stroup BM, Poliner A, et al. Liver transplantation in propionic and methylmalonic acidemia: a single center study with literature review. Mol Genet Metab 2019;128(4):431-43. PMID 31757659
- 147
- Prasad C, Nurko S, Borovoy J, Korson MS. The importance of gut motility in the metabolic control of propionic acidemia. J Pediatr 2004;144(4):532-5. PMID 15069406
- 148
- Rafique M. Propionic acidaemia: demographic characteristics and complications. J Pediatr Endocrinol Metab 2013;26(5-6):497-501. PMID 23509210
- 149
- Rajakumar A, Kaliamoorthy I, Reddy MS, Rela M. Anaesthetic considerations for liver transplantation in propionic acidemia. Indian J Anaesth 2016;60(1):50-4. PMID 26962256
- 150
- Ramachandran R, Pietz J. Propionic acidemia without acidemia: a case report. J Perinatol 1995;15:71-3. PMID 7650559
- 151
- Rashed MS, Ozand PT, Bucknall MP, Little D. Diagnosis of inborn errors of metabolism from blood spots by acylcarnitines and amino acids profiling using automated electrospray tandem mass spectrometry. Pediatr Res 1995;38:324-31. PMID 7494654
- 152
- Ravn K, Chloupkova M, Christensen E, et al. High incidence of propionic acidemia in Greenland is due to a prevalent mutation, 1540insCCC, in the gene for the beta-subunit of propionyl CoA carboxylase. Am J Hum Genet 2000;67:203-6. PMID 10820128
- 153
- Rela M, Battula N, Madanur M, et al. Auxiliary liver transplantation for propionic acidemia: a 10-year follow-up. Am J Transplant 2007;7(9):2200-3. PMID 17697263
- 154
- Richard E, Desviat LR, Perez B, Perez-Cerda C, Uqarte M. Three novel splice mutations in the PCCA gene causing identical exon skipping in propionic acidemia patients. Hum Genet 1997;101:93-6. PMID 9385377
- 155
- Richard E, Desviat LR, Perez B, Perez-Cerda C, Ugarte M. Genetic heterogeneity in propionic acidemia patients with alpha-subunit defects. Identification of five novel mutations, one of them causing instability of the protein. Biochim Biophys Acta 1999;1453:351-8. PMID 10101253
- 156
- Riemersma M, Hazebroek MR, Helderman-van den Enden ATJM, et al. Propionic acidemia as a cause of adult-onset dilated cardiomyopathy. Eur J Hum Genet 2017;25(11):1195-201. PMID 28853722
- 157
- Rivera-Barahona A, Navarrete R, García-Rodríguez R, et al. Identification of 34 novel mutations in propionic acidemia: functional characterization of missense variants and phenotype associations. Mol Genet Metab 2018;125(3):266-75. PMID 30274917
- 158
- Robert MF, Schultz DJ, Wolf B, Cochran WD, Schwartz AL. Treatment of a neonate with propionic acidaemia and severe hyperammonaemia by peritoneal dialysis. Arch Dis Child 1979;54(12):962-5. PMID 533302
- 159
- Rodriguez-Pombo P, Perez-Cerda C, Perez B, Desviat LR, Sanchez-Pulido L, Ugarte M. Towards a model to explain the intragenic complementation in the heteromultimeric protein propionyl-CoA carboxylase. Biochim Biophys Acta 2005;1740(3):489-98. PMID 15949719
- 160
- Roe CR, Bohan TP. L-carnitine therapy in propionic acidemia. Lancet 1982;1:1411-2. PMID 6123699
- 161
- Romano S, Valayannopoulos V, Touati G, et al. Cardiomyopathies in propionic aciduria are reversible after liver transplantation. J Pediatr 2010;156(1):128-34. PMID 19818452
- 162
- Rosenberg LE. Disorders of propionate and methylmalonate metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic Basis of Inherited Disease. New York: McGraw-Hill, 1989:821-44.
- 163
- Rosenberg LE, Lilljeqvist A, Hsia YE. Methylmalonic aciduria. An inborn error leading to metabolic acidosis, long chain ketonuria, and intermittent hyperglycinemia. N Engl J Med 1968;278:1319-22. PMID 5648598
- 164
- Rousson R, Guiband P. Long term outcome of organic acidurias: survey of 105 French cases (1967-1983). J Inherit Metab Dis 1984;7:10-2. PMID 6434836
- 165
- Sass JO, Hofmann M, Skladal D, Mayatepek E, Schwahn B, Sperl W. Propionic acidemia revisited: a workshop report. Clin Pediatr 2004;43(9):837-43. PMID 15583780
- 166
- Sato S, Kasahara M, Fukuda A, et al. Liver transplantation in a patient with propionic acidemia requiring extra corporeal membrane oxygenation during severe metabolic decompensation. Pediatr Transplant 2009;13(6):790-3. PMID 19207227
- 167
- Saudubray JM, Touati G, Delonlay P, et al. Liver transplantation in propionic acidaemia. Eur J Pediatr 1999;158(Suppl 2):S65-9. PMID 10603102
- 168
- Scholl-Burgi S, Haberlandt E, Gotwald T, et al. Stroke-like episodes in propionic acidemia caused by central focal metabolic decompensation. Neuropediatrics 2009;40(2):76-81. PMID 19809936
- 169
- Schwahn BC, Pieterse L, Bisset WM, Galloway PG, Robinson PH. Biochemical efficacy of N-carbamylglutamate in neonatal severe hyperammonaemia due to propionic acidaemia. Eur J Pediatr 2010;169(1):133-4. PMID 19680687
- 170
- Sethi KD, Ray R, Roesel RA, et al. Adult-onset chorea and dementia with propionic acidemia. Neurology 1989;39:1343-5. PMID 2797456
- 171
- Shafai T, Sweetman L, Weyler W, Goodman SI, Fennessey PV, Nyhan WL. Propionic acidemia with severe hyperammonemia and defective glycine metabolism. Pediatrics 1963;92:84-6. PMID 619088
- 172
- Shigematsu Y, Hata I, Nakai A, et al. Prenatal diagnosis of organic acidemias based on amniotic fluid levels of acylcarnitines. Pediatr Res 1996;39:680-4. PMID 8848345
- 173
- Shigematsu Y, Hirano S, Hata I, et al. Newborn mass screening and selective screening using electrospray tandem mass spectrometry in Japan. J Chromatogr B Analyt Technol Biomed Life Sci 2002;776:39-48. PMID 12127323
- 174
- Shuaib T, Al-Hashmi N, Ghaziuddin M, et al. Propionic acidemia associated with visual hallucinations. J Child Neurol 2012;27:799-803. PMID 22156789
- 175
- Shuman RM, Leech RW, Scott CR. The neuropathology of the nonketotic and ketotic hyperglycinemias: three cases. Neurology 1978;28:139-46. PMID 563996
- 176
- Sivananthan S, Hadžić N, Dhawan A, Heaton N, Vara R. Fatal metabolic stroke in a child with propionic acidemia 11 years post liver transplant. Am J Transplant 2021;21:1637-40. PMID 33205569
- 177
- Soberón JR, Elliott CE, Bland KS, Weinberg GL. Peripheral nerve block in a patient with propionic acidemia. Reg Anesth Pain Med 2014;39:560-1. PMID 25340489
- 178
- Soyucen E, Demirci E, Aydin A. Outpatient treatment of propionic acidemia-associated hyperammonemia with N-carbamoyl-L-glutamate in an infant. Clin Ther 2010;32(4):710-3. PMID 20435240
- 179
- Stanescu S, Belanger-Quintana A, Fernández-Felix BM, et al. Long-term follow-up with filter paper samples in patients with propionic acidemia. JIMD Rep 2020;57:44-51. PMID 33473339
- 180
- Stanescu S, Belanger-Quintana A, Fernández-Felix BM, et al. Plasma CoQ10 status in patients with propionic acidaemia and possible benefit of treatment with ubiquinol. Antioxidants (Basel) 2022;11(8):1588. PMID 36009307
- 181
- Stigsby B, Yarworth SM, Rahbeeni Z, et al. Neurophysiologic correlates of organic acidemias: a survey of 107 patients. Brain Dev 1994;16:125-44. PMID 7726377
- 182
- Stojiljkovic M, Klaassen K, Djordjevic M, et al. Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias. Clin Genet 2016;90(3):252-7. PMID 26830710
- 183
- Stork LC, Ambruso DR, Wallner SF, et al. Pancytopenia in propionic acidemia: hematologic evaluation and studies of hematopoiesis in vitro. Pediatr Res 1986;8:783-8. PMID 3737292
- 184
- Surtees RA, Mathews EE, Leonard JV. Neurologic outcome of propionic acidemia. Pediatr Neurol 1992;8:333-7. PMID 1418175
- 185
- Sweetman L, Nyhan WL, Cravens J, Zomer Y, Plunket DC. Propionic acidaemia presenting with pancytopaenia in infancy. J Inherit Metab Dis 1979a;2:65-9. PMID 6796762
- 186
- Sweetman L, Weyler W, Shafai T, Young PE, Nyhan WL. Prenatal diagnosis of propionic acidemia. JAMA 1979b;242:1048-52. PMID 470045
- 187
- Tahara T, Kraus JP, Rosenberg LE. An unusual insertion/deletion in the gene encoding the beta-subunit of propionyl-CoA carboxylase is a frequent mutation in the Caucasian propionic acidemia. Proc Natl Acad Sci U S A 1990;87:1372-6. PMID 2154743
- 188
- Thomas E. A study of the response to protein-modified diets for propionic acidemia in twelve patients. Brain Dev 1994;16:58-63. PMID 7726382
- 189
- Tummolo A, Melpignano L, Carella A, et al. Long-term continuous N-carbamylglutamate treatment in frequently decompensated propionic acidemia: a case report. J Med Case Rep 2018;12(1):103. PMID 29679984
- 190
- Ugarte M, Perez-Cerda C, Rodriguez-Pombo P, et al. Overview of mutations in the PCCA and PCCB genes causing propionic acidemia. Hum Mutat 1999;4:275-82. PMID 10502773
- 191
- Van Calcar SC, Harding CO, Davidson SR, Barness LA, Wolff JA. Case reports of successful pregnancy in women with maple syrup urine disease and propionic acidemia. Am J Hum Genet 1992;44:641-6. PMID 1481826
- 192
- Vara R, Turner C, Mundy H, et al. Liver transplantation for propionic acidemia in children. Liver Transpl 2011;17(6):661-7. PMID 21618686
- 193
- Vatanavicharn N, Liammongkolkul S, Sakamoto O, Kamolsilp M, Sathienkijkanchai A, Wasant P. Clinical characteristics and mutation analysis of propionic acidemia in Thailand. World J Pediatr 2014;10:64-8. PMID 24464666
- 194
- Velasco-Sanchez D, Gómez-Lopez L, Vilaseca MA, et al. Cerebellar hemorrhage in a patient with propionic acidemia. Cerebellum 2009;8(3):352-4. PMID 19468795
- 195
- Vernon HJ, Bagnasco S, Hamosh A, Sperati CJ. Chronic kidney disease in an adult with propionic acidemia. JIMD Rep 2014;12:5-10. PMID 23756992
- 196
- Wadlington WB, Kilroy A, Ando T, Sweetman L, Nyhan WL. Hyperglycinemia and propionyl CoA carboxylase deficiency and episodic severe illness without consistent ketosis. J Pediatr 1975;86:707-12. PMID 1133651
- 197
- Wajner M, Goodman SI. Disruption of mitochondrial homeostasis in organic acidurias: insights from human and animal studies. J Bioenerg Biomembr 2011;43(1):31-8. PMID 21249436
- 198
- Wang H, Meng L, Li W, et al. Combinations of exonic deletions and rare mutations lead to misdiagnosis of propionic acidemia. Clin Chim Acta 2020;502:153-8. PMID 31893529
- 199
- Werlin SL. E. coli sepsis as a presenting sign in neonatal propionic acidemia. Am J Med Genet 1993;46:455-6. PMID 8357022
- 200
- Willard HF, Ambani LM, Hart AC, Mahoney MJ, Rosenberg LE. Rapid prenatal and postnatal detection of inborn errors of propionate, methylmalonate, and cobalamin metabolism. Hum Genet 1976;34:277-83. PMID 1002151
- 201
- Williams ZR, Hurley PE, Altiparmak UE, et al. Late onset optic neuropathy in methylmalonic and propionic acidemia. Am J Ophthalmol 2009;147(5):929-33. PMID 19243738
- 202
- Witters P, Debbold E, Crivelly K, et al. Autism in patients with propionic acidemia. Mol Genet Metab 2016;119(4):317-21. PMID 27825584
- 203
- Wolf B. Reassessment of biotin-responsiveness in "unresponsive" propionyl CoA carboxylase deficiency. J Pediatr 1980;97:964-6. PMID 7441430
- 204
- Wolf B, Hsia YE. Biotin-responsiveness in propionic acidemia. Lancet 1978;2:901. PMID 81453
- 205
- Wolf B, Hsia YE, Sweetman L, Gravel R, Harris DJ, Nyhan WL. Propionic acidemia: a clinical update. J Pediatr 1981;99:835-46. PMID 7031206
- 206
- Wolf B, Hsia YE, Tanaka K, Rosenberg LE. Correlation between serum propionate and blood ammonia concentrations in propionic acidemia. J Pediatr 1978a;93:471-3. PMID 690769
- 207
- Wolf B, Paulsen EP, Hsia YE. Asymptomatic propionyl CoA carboxylase deficiency in a 13-year-old girl. J Pediatr 1979;95:563-5. PMID 480035
- 208
- Wolf B, Rosenberg LE. Heterozygote expression in propionyl coenzyme A carboxylase deficiency. J Clin Invest 1978b;62:931-6. PMID 711858
- 209
- Wolf B, Willard HF, Rosenberg LE. Kinetic analysis of genetic complementation in heterokaryons of propionyl CoA carboxylase-deficient human fibroblasts. Am J Hum Genet 1980;32:16-25. PMID 7361761
- 210
- Wongkittichote P, Ah Mew N, Chapman KA. Propionyl-CoA carboxylase - A review. Mol Genet Metab 2017;122(4):145-52. PMID 29033250
- 211
- Worthen HG, al Ashwal A, Ozand PT, et al. Comparative frequency and severity of hypoglycemia in selected organic acidemias, branched chain amino acidemia, and disorders of fructose metabolism. Brain Dev 1994;16:81-5. PMID 7726385
- 212
- Yang X, Sakamoto O, Matsubara Y, et al. Mutation spectrum of the PCCA and PCCB genes in Japanese patients with propionic acidemia. Mol Genet Metab 2004;81:335-42. PMID 15059621
- 213
- Yano S, Li L, Le TP, et al. J Infantile mitochondrial DNA depletion syndrome associated with methylmalonic aciduria and 3-methylcrotonyl-CoA and propionyl-CoA carboxylase deficiencies in two unrelated patients: a new phenotype of mtDNA depletion syndrome. Inherit Metab Dis 2003;26:481-8. PMID 14518828
- 214
- Yap S, Vara R, Morais A. Post-transplantation outcomes in patients with PA and MMA: A review of the literature. Mol Genet Metab 2020;130(3):183-96. PMID 32270363
- 215
- Yorifuji T, Kawai M, Muroi J, et al. Unexpectedly high prevalence of the mild form of propionic acidemia in Japan: presence of a common mutation and possible clinical implications. Hum Genet 2002;111:161-5. PMID 12189489
- 216
- Yorifuji T, Muroi J, Uematsu A, Nakahata T, Egawa H, Tanaka K. Living-related liver transplantation for neonatal-onset propionic acidemia. J Pediatr 2000;137:572-4. PMID 11035841
- 217
- Zeng ZG, Zhou GP, Wei L, et al. Therapeutic potential of living donor liver transplantation from heterozygous carrier donors in children with propionic acidemia. Orphanet J Rare Dis 2022;17(1):62. PMID 35189944
- 218
- Zhou GP, Jiang YZ, Wu SS, Kong YY, Sun LY, Zhu ZJ. Liver transplantation for propionic acidemia: evidence from a systematic review and meta-analysis. Transplantation 2021;105:2272-82. PMID 33093405
Contributors
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Author
-
Barry Wolf MD PhD
Dr. Wolf of Lurie Children's Hospital of Chicago has no relevant financial relationships to disclose.
See Profile
Patient Profile
- Age range of presentation
-
- 0 month to 44 years
- Sex preponderance
-
- male=female
- Heredity
-
- heredity typical
- heredity may be a factor
- Population groups selectively affected
-
- none selectively affected
- Occupation groups selectively affected
-
- none selectively affected
ICD & OMIM codes
- ICD-9
-
- Disturbances of branched-chain amino-acid metabolism: 270.3
- ICD-10
-
- Other disorders of branched-chain amino-acid metabolism: E71.1
- OMIM
-
- Propionyl-CoA carboxylase deficiency type I: *232000
- Propionyl-CoA carboxylase deficiency type II: *232050
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