Cockayne syndrome
May. 08, 2026
Worddefinition
At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas.
GABA-transaminase deficiency
- Updated 12.22.2025
- Released 03.21.1994
- Expires For CME 12.22.2028
GABA-transaminase deficiency
Introduction
Overview
GABA-transaminase deficiency is a rare GABA metabolism disorder that combines neonatal encephalopathy, hypotonia, and epilepsy. In this article, the authors review this enigmatic pediatric neurotransmitter disorder. Patients manifest global developmental impairment, seizures, hypotonia, hyperreflexia, extrapyramidal manifestations, and lethargy. Urine amino acids may show elevated GABA, homocarnosine, and beta-alanine. Differential diagnosis includes succinic semialdehyde dehydrogenase deficiency (SSADHD), cerebral gigantism, globoid cell leukodystrophy, and Pelizaeus-Merzbacher disease. GABA-transaminase deficiency can be diagnosed through accurate determination of elevated CSF GABA and beta-alanine, which is performed by liquid chromatography-electrospray-tandem mass spectrometry (01), although it is now more typically identified using exome or genome sequencing. As opposed to succinic semialdehyde dehydrogenase deficiency, which is diagnosed by elevated urinary γ-hydroxybutyrate (GHB), the GHB levels in GABA-transaminase deficiency are low.
Key points
|
• GABA-transaminase deficiency is inherited as an autosomal recessive disorder. | |
|
• This disorder is characterized by high levels of GABA in serum and CSF. | |
|
• Patients manifest with profoundly abnormal development, epileptic seizures, and choreoathetosis. |
Historical note and terminology
GABA-transaminase deficiency was initially reported in two of four siblings in a single Flemish family (18). Only the female, who died at 2 years of age, was confirmed enzymatically. An older brother, who died previously at 1 year of age, had similar clinical symptomatology. A report and literature review subsequently published 10 cases, including the original family noted above (23).
Clinical manifestations
Presentation and course
Patients present with neonatal or early infantile onset encephalopathy with inability to visually track, generalized tonic-clonic seizures, hypotonia, choreoathetosis, and subcortical myoclonus. Accelerated growth has been documented, as well as delayed cerebral myelination (35; 23). In the index family, both affected siblings had neonatal seizures, lethargy, hypotonia, hyperreflexia, poor feeding, severely delayed psychomotor development, and a high-pitched cry (18; 11; 17; 17; 10; 32; 20; 38). Linear growth and head circumference were accelerated, consistent with the growth-hormone promoting effects of GABA, with adiposity and intermittent hepatomegaly noted in the female proband (36). EEG in the female was normal at 2 weeks of age, revealed predominantly low-voltage beta-frequency activity with intermittent epileptiform discharges at 7 months, and showed generalized epileptiform paroxysms at 2 years. Visual, auditory, and somatosensory evoked potentials were absent at the age of 2 years. CT in both siblings revealed severe ventricular enlargement as well as increased cisternal and sulcal spaces.
Next, a 6745 gram Japanese female was born to healthy, nonconsanguineous Japanese parents with no family history of neurologic disorders (43). The patient had an uncomplicated birth and normal early infancy but was evaluated at 7 months for hyperreflexia, developmental delay, hypotonia, bilateral intermittent esotropia, and a positive Babinski reflex. No dysmorphic features were noted. At 8 months of age, the patient was hospitalized for decreased consciousness after the onset of a febrile illness. She developed respiratory distress and required mechanical ventilation. She began to experience segmental myoclonic jerks that were partially controlled by phenobarbital, clonazepam, valproate, or midazolam. EEG revealed diffuse spike-and-wave activity with 1- to 2-second periods of background suppression. At 11 months, the patient experienced chronic respiratory failure, and the febrile illness resulted in neurodegeneration characterized by opisthotonic posturing with generalized dystonia and continued segmental myoclonus. Free GABA was elevated in serum, CSF, and cortical tissue, whereas GABA-transaminase activity was diminished. CT was normal, and the brain MRI suggested a mild delay in myelination, but no structural abnormalities. Follow-up was reported at 9 years of age with profound neurodevelopmental impairment, active generalized tonic-clonic seizures, and a medication program of phenobarbital, clonazepam, diazepam, baclofen, dantrolene, and haloperidol. Diagnostic findings include significantly elevated GABA (free and total) and beta-alanine levels in plasma and CSF, as well as diminished GABA-transaminase enzymatic activity. In both the female index patient and the unrelated case, CSF free-GABA was the most elevated biological marker at 60x and 16x elevated levels, respectively. CSF bound, plasma bound, and plasma free GABA were also markedly elevated, at levels at least three times the normal range (18; 20; 43). Tsuji and colleagues used quantitative proton magnetic resonance spectroscopy (1H-MRS) to detect the GABA concentration in the basal ganglia of their patient (43).
A 12-month-old male diagnosed postmortem was reported with neonatal generalized tonic-clonic seizures, hypotonia, accelerated growth, lethargy, and cerebral atrophy without developmental progress (24). In another family, two siblings presented at 3 months of age with profound impairment, seizures, hypotonia, lethargy, and cerebral atrophy. The female died at 7 years of age; the male was alive at this age (06). Both had free CSF GABA levels that were more than twice the upper limit of normal (2.9 and 3.1 ULN = 1.4). A 2016 paper reported a third sibling of the above two patients, who presented at 2 months with a highly similar clinical presentation to the two siblings previously discussed and died at 12 months (05). This paper also reported a patient with a milder clinical presentation. This 6-month-old male presented with hypotonia, hypersomnolence, developmental delay, and mild chorea. No structural brain abnormalities were noted, but a cranial MRI at 9 months showed delayed myelination. Unlike the previously reported patients, he reached developmental milestones and could control his head when sitting, track faces, smile appropriately, and eat and drink solid food by mouth by 18 months. Though EEG showed hypsarrhythmia, he did not present with overt seizures (05).
Nagappa and colleagues described a female neonate that presented with global developmental delay, hypersomnolence, hypotonia, and a hyperkinetic movement disorder with choreoathetosis that subsided during sleep (31). EEG was normal at 6 months but showed multifocal epileptiform spikes at 18 months. MRI showed increased T2/FLAIR signal with T1 hypointensity, interpreted as dysmyelination, affecting the medulla, dorsal pons, cerebellar dentate nucleus, and internal capsule (anterior limb and genu). A trilaminated appearance was present based on central hypointensity and hyperintense margins involving the posterior limb of the internal capsule. In 2019, Morales-Briceño and colleagues described previously unreported findings of paroxysmal dyskinesias associated with drowsiness and T2 thalamic hyperintensities in two adult siblings, 32- and 25-year-old sisters with history of mild developmental delays and seizures (29).
A series published in 2017 reported a boy born to consanguineous parents who presented at 5 months with developmental delay, hypotonia, hypersomnolence, choreoathetosis, and focal seizures (23). Seizure types expanded to include generalized tonic-clonic at 2 years and absence as well as generalized convulsive status epilepticus at 6 years. Cranial MRI showed progressive atrophy at 4 years. In the same series, four out of the 10 patients were deceased by 25 months. The five surviving cases were ages 18 months to 9.5 years at the time of the report. Recent years have shown the emergence of milder phenotypes, associated with higher residual enzymatic activity and survival into adulthood (15; 29).
In 2020, another neonatal case of genetically confirmed GABA-transaminase deficiency was reported, with a description including severe neonatal epileptic encephalopathy, lethargy, hypotonia, hyperreflexia, and poor feeding (33). An MRI revealed potentially coincidental extensive intraventricular hemorrhage. At 14 days of age, he developed polyuria and hypernatremia with a low antidiuretic hormone serum level, corresponding to diabetes insipidus. He was treated with desmopressin until his death at 7 months. An exome study detected homozygosity of the c.316G > A (p.Gly106Ser) variant in the ABAT gene. Both consanguineous parents were heterozygous carriers of this variant.
An additional case report from 2023 described a 4-year-old boy from India born to nonconsanguineous parents (13). He presented with global developmental delay, drug-resistant seizures, and excessive sleep. Examination revealed mild dysmorphic features, upper motor neuron and cerebellar signs, and autism. An EEG captured multifocal and generalized epileptiform patterns, and a brain MRI demonstrated mild hyperintensity in the superior cerebellar area. Exome sequencing identified compound heterozygosity of the variants c.43C>T:pGln15Ter and c.1295C>T:p.Thr432Ile (13).
Increasing the use of sequencing of the ABAT gene is expected to identify new cases. To confirm the pathogenic sequencing findings, CSF quantification of GABA-free and total levels is recommended. Definitive diagnosis can also be made by measuring GABA-T activity in the liver, lymphocytes isolated from whole blood, or Epstein-Barr virus-transformed cultured lymphoblasts (12).
Prognosis and complications
Patients have uniformly presented with neonatal or early infantile encephalopathy, often accompanied by hypotonia, lethargy, seizures, and extrapyramidal manifestations. In the first reported family, their oldest child died at 5 days of age from an unknown cause without sufficient clinical history to establish a retrospective diagnosis. GABA-transaminase deficiency appears to be extremely rare, although it is possible that the inborn error is lethal in utero or very early in the neonatal period, before a metabolic diagnosis is made. Additionally, CSF GABA levels are not measured routinely in patients with epileptic encephalopathies, and the disorder may be undetected.
Clinical vignette
An 8-year-old boy born to consanguineous parents (first cousins) presented at 5 months of age with developmental delay, hypotonia, excessive daytime somnolence, and virtually continuous movements in the awake state consistent with choreoathetosis. Generalized seizures ensued by age 2 years, and EEGs showed multifocal discharges and diffuse slowing. MRI demonstrated progressive atrophy. Whole exome sequencing demonstrated a novel homozygous variant in ABAT (c.1129C> T; p.R377W). Parents were confirmed as heterozygous carriers.
Biological basis
Etiology and pathogenesis
GABA-transaminase deficiency is a rare autosomal recessive disorder characterized by a defect in the major GABA degradative pathway (E.C. 2.6.1.19). Normally, GABA is converted to succinic semialdehyde, an unstable intermediate, by GABA-transaminase, and then to succinic acid, which enters the tricarboxylic acid cycle (34). This process leads to the conversion of alpha-ketoglutarate to glutamate, one step within the GABA shunt pathway where each molecule of GABA that is metabolized leads to the synthesis of a molecule of glutamate, which is then converted to GABA via glutamic acid decarboxylase. Hence, GABA-transaminase is a vital enzyme in the intricate balance of the brain’s excitatory-inhibitory balance, responsible for the catabolism and regulation of GABA (08).
Compared to control levels, the index female patient showed markedly elevated CSF concentrations of free GABA (60-fold), homocarnosine (3-fold), and beta-alanine (10-fold) (20). Her CSF also contained increased amounts of unidentified GABA conjugates, ornithine, and putrescine (18). Plasma analysis revealed free GABA and beta-alanine concentrations elevated 10- and 4-fold, respectively, alongside fasting plasma growth hormone levels ranging from 8 to 38 ng/mL (normal < 5 ng/mL). Urinalysis demonstrated elevated GABA, beta-alanine, beta-aminoisobutyric acid, and taurine (18). In an unrelated patient, free GABA was increased nearly 7-fold in plasma and 16-fold in CSF (43). Elevated 2-pyrrolidionone–a more stable, blood-brain-barrier permeable cyclization product of GABA–was found in two patients, at levels above two standard deviations from the control mean. The administration of flumazenil did not alter levels (22). Kennedy and colleagues also described similar findings in CSF and urine in three of four patients, with elevated 2-pyrrolidinone (average of over four standard deviations beyond the control mean) and succinamic acid in the plasma. To validate results, this elevation of 2-pyrrolidinone was also observed in patients taking vigabatrin, an antiseizure medication that inhibits GABA-transaminase. Although 2-pyrrolidinone was elevated with the administration of other antiseizure medications, the difference was not significantly higher as was seen with GABA-T deficiency and vigabatrin (21). Thus, 2-pyrrolidinone has the potential to be a biomarker for GABA and can be utilized to identify elevations in GABA from noninvasive testing of a plasma or urine sample for diagnosis of GABA-transaminase deficiency.
GABA-transaminase deficiency was documented in the first proband from enzyme activity measurements in biopsied liver, lymphocytes isolated from whole blood, and Epstein-Barr virus-transformed cultured lymphoblasts, showing approximately 15% of normal controls (18; 12). Mean GABA-transaminase activity was 1.2 protein pmol/h/mg (range 20 to 50) in the original female proband and 2 protein pmol/h/mg (range 23 to 64) in the unrelated patient (43). The neurologic manifestations are likely due to elevated CNS concentrations of GABA and possibly beta-alanine, whereas less elevated levels of homocarnosine appear unrelated to symptoms (40). Length-growth acceleration, though an unusual feature for an early onset epileptic encephalopathy, is consistent with GABA’s growth hormone releasing effects, and is likely a consequence of growth hormone hypersecretion (37; 36). The severity of encephalopathy and involuntary hyperkinetic movements may correlate with basal ganglia GABA levels, which peak between ages 1 and 2 before declining with age (16).
Postmortem findings in a male patient of 1 year revealed well-developed subcutaneous fat, brain edema, thymus enlargement, bronchopneumonia, and small regions of hepatic necrosis. In the same patient, neuropathologic examination revealed poor or absent myelination in gyral white matter. Even where well-myelinated, a spongy state of varying degrees was present throughout the white matter of the cerebral hemispheres, cerebellum, and brainstem, sparing the arcuate fibers (18). An autopsy was not performed on the patient’s sister. The disorder is inherited in an autosomal recessive manner, with the carrier parents of the first described family showing intermediate GABA-T activity between the female patient and the control range (12).
Molecular investigations by Medina-Kauwe and colleagues identified an A-to-G transition at nucleotide 754 of the human GABA-transaminase gene in lymphoblast cDNA (c.754A> G) of the index proband, resulting in p.Arg220Lys (27; 28). This mutation destabilizes the binding of pyridoxal-5’-phosphate to GABA-transaminase. A second allele in this patient was later identified as c.1433T>C, causing the substitution p.Leu478Pro. In the second family, Tsuji reported compound heterozygosity for c.275G>A that causes the substitution p.Arg92Gl and an unspecific exon deletion around nucleotides 199 to 316 of the GABA-transaminase coding region (43). Besse and colleagues found GABA-transaminase functions in both the known GABA catabolism and newly reported mitochondrial nucleoside salvage pathways after localizing activity to the mitochondrial matrix (06). Fibroblast in vitro studies showed a low mitochondrial DNA copy number, which was corrected by delivering wild-type GABA-transaminase. A similar depletion of mitochondrial DNA was reported in murine retinal cells after pharmacological inhibition of GABA-transaminase by administering vigabatrin, which when administered with nucleotides, prevented mtDNA depletion and presented a potential therapeutic for vigabatrin-related retinopathy with associated visual field defects.
Interestingly, in recent years, GABA-transaminase has also been found to have an association with other medical conditions, including Alzheimer disease, tumorigenesis, hepatocellular carcinoma, and medulloblastoma metastasis (26; 45; 09). GABA-transaminase has also been associated with weight loss; an investigation showed that GABA transaminase inhibitors lead to increased GABA effectively suppress food intake and promote weight loss in obese murine models (30; 04).
Epidemiology
GABA-T deficiency is an extremely rare autosomal recessive disease, with several case reports and small series published thus far (23; 15; 16; 29). The oldest identified patient was 32 years of age at the time reported (21; 29).
Prevention
Only parents who are asymptomatic heterozygote carriers for GABA-transaminase deficiency could give rise to an affected child, with each pregnancy having a one in four chance of producing an affected fetus. Genetic counseling for a family with a previously documented proband is recommended. The potential for prenatal diagnosis by means of chorionic villus sampling has been presented (41). The possibility of prenatal diagnosis by measuring amniotic fluid levels of GABA and beta-alanine may also exist (34).
Differential diagnosis
GABA-transaminase deficiency could be confused with hyper-beta-alaninemia (39). Despite certain similarities in clinical and metabolic presentation, there are various differences between the two disorders: linear growth is increased in GABA-transaminase deficiency but delayed in hyper-beta-alaninemia; CSF beta-alanine concentrations were reported two orders of magnitude higher in hyper-beta-alaninemia than the (index) patient with GABA-transaminase deficiency; and the urinary metabolite profile, including the concentrations of GABA, beta-alanine and beta-aminoisobutyric acid, were different in the two disorders. Impaired transamination of beta-alanine was suggested as the primary defect in hyper-beta-alaninemia (39; 38). It remains possible that hyper-beta-alaninemia is a variant form of GABA-transaminase deficiency.
Patients with semialdehyde dehydrogenase deficiency may present with elevated quantities of urinary beta-alanine and beta-aminoisobutyric acid, which may suggest GABA-transaminase deficiency in the differential diagnosis (34). However, these patients present with organic aciduria, often characterized by increased urinary 4-hydroxybutyric, 3-hydroxyisobutyric, 2-ethylhydracrylic, 3-hydroxypropionic, and 3,4-dihydroxyhexanoic acids. The patient with GABA-transaminase deficiency manifests amino aciduria, not organic aciduria.
Jaeken and coworkers noted that a qualitative biochemical profile similar to that seen in GABA-transaminase deficiency, including increases in GABA, GABA-conjugates, and beta-alanine, is detected in the CSF of patients treated with the GABA-transaminase inhibitor gamma-vinyl-GABA (vigabatrin), an antiseizure medicine used for epileptic spasms as well as focal onset seizures (17). However, the relative increase in free GABA is much less pronounced than in GABA-transaminase deficiency (14).
Clinically, the disorder may resemble cerebral gigantism, certain leukodystrophies (including globoid cell leukodystrophy, adult-onset progressive dominant leukodystrophy, and Pelizaeus-Merzbacher disease), or adult-onset progressive dominant leukodystrophy. These can be excluded by specific clinical and metabolite features: cerebral gigantism lacks a biochemical marker, Krabbe disease is associated with galactocerebrosidase deficiency, adult-onset progressive dominant leukodystrophy presents later, and Pelizaeus-Merzbacher disease manifests an unusual pendular nystagmus with X-linked inheritance (03; 02; 25; 07).
Lastly, succinic semialdehyde dehydrogenase (SSADH) deficiency, another GABA metabolic pathway disorder, also elevates GABA but is differentiated by the build-up of gamma-hydroxybutyrate (GHB), a metabolite of GABA, which does not accumulate in GABA-transaminase deficiency. Repeated organic acid analysis of urine is the most reliable method of determining excess GHB, and inherited gamma hydroxybutyric aciduria should be distinguished from exogenous use of GHB, either for pharmacologic purposes in the treatment of narcolepsy-cataplexy or as a drug of abuse (35).
Diagnostic workup
Diagnosis will be made in most cases by whole exome or genome sequencing, with identification of biallelic ABAT pathogenic variants. GABA-transaminase deficiency is not associated with acidosis, hypoglycemia, ketosis, or hyperammonemia, abnormalities often considered in the differential diagnosis of inborn metabolic errors. Quantitative plasma testing and quantitative CSF amino acid analysis should be considered in patients presenting with psychomotor deficits, hypotonia, accelerated length-growth, and hyperreflexia. The detection of increased GABA and beta-alanine in urine would warrant the analysis of plasma and CSF amino acid concentrations. A pitfall in determining free GABA concentrations in CSF is the enzymatic degradation of homocarnosine, a dipeptide of GABA and L-histidine. Accurate free CSF GABA measurement requires deep freezing (-20°C short-term or -70°C long-term) for a few minutes. It may also be of value to determine the fasting level of plasma growth hormone. Elevated fasting plasma growth hormone is consistent with the growth hormone-releasing effect of GABA and may suggest GABA-transaminase deficiency in the differential diagnosis (36). Detection of increased GABA and beta-alanine in CSF could be further investigated for assessment of GABA-transaminase activity in isolated lymphocytes or Epstein-Barr virus-transformed lymphoblasts. Tsuji and colleagues utilized quantitative [1H]MR spectroscopy to measure GABA concentrations in brain parenchyma in vivo (43).
Untargeted metabolomics may serve as a useful screening method for inherited metabolic disorders. An automated computational diagnostic method has shown to have the capacity to connect pieces of information derived from metabolite perturbations observed in individual metabolomics profiling data and modules identified in disease-specific metabolite co‑perturbation networks. This has demonstrated the ability to reproduce an accurate diagnosis in known as well as newly identified inherited metabolic disorders, including GABA-transaminase deficiency (42).
Additional light has been shed on the underlying pathomechanism of GABA-transaminase deficiency. This was achieved through a computational based methodology examining the molecular dynamics, structural stability, and binding free energy of GABA-transaminase deficiency’s pathogenic variants (44). A 3D model of the GABA transaminase enzyme was created, as well as seven other versions of GABA-transaminase enzymes, each with a different structural abnormality. The structural stability of all the predicted models was analyzed and evaluated based on their phytochemical values and calculated free energy. The findings of the investigation showed that the models resulting from the pathogenic variants P152S, Q296H, and R92Q led to greater degrees of structural instability of the GABA transaminase enzyme compared those derived from G465R, L211F, L478P, and R220K. Future studies may explore the relationships between these pathogenic variants and clinical outcomes. This will have value for prognostication and perhaps targeted drug-development.
Management
Trials with pyridoxine (up to 3 g/day) as well as picrotoxin (up to 0.12 mg/kg per day) did not improve the clinical situation in the index case. Two reported patients have received trials of flumazenil, antagonist of the benzodiazepine binding site of the GABA(A) receptor. One appears to have responded to a regimen involving an initial bolus of 0.01 mg/kg intravenously in an intensive care unit setting and maintained on 1.7 mg/kg/day with an 11-month ongoing course of treatment (23). The other patient discontinued the medicine following a 2-month trial due to increased wakefulness with agitation and no observed benefit.
References
- 01
- Arning E, Wasek B, Bottiglieri T. Quantitation of γ-aminobutyric acid in cerebrospinal fluid using liquid chromatography-electrospray-tandem mass spectrometry. In: Clinical applications of mass spectrometry in biomolecular analysis. New York: Springer, 2022:165-74.
- 02
- Ashrafi MR, Mohammadi M, Alizadeh H, Nikkhah A. Pelizaeus-merzbacher disease: the first genetically approved case report from Iran. Iran J Pediatr 2011;21(3):395-8. PMID 23056820
- 03
- Baujat G, Cormier-Daire V. Sotos syndrome. Orphanet J Rare Dis 2007;2:36. PMID 17825104
- 04
- Begazo-Jimenez R, Yu A, Gros R, Lu WY. Long-term supplementation of GABA regulates growth, food intake, locomotion, and lipid metabolism by increasing Ghrelin and growth hormone in adolescent mice. Nutrients 2025;17(10):1634. PMID 40431374
- 05
- Besse A, Peterson AK, Hunter JV, Appadurai V, Lalani SR, Bonnen PE. Personalized medicine approach confirms a milder case of ABAT deficiency. Molec Brain 2016;9(1):93-103. PMID 27903293
- 06
- Besse A, Wu P, Bruni F, et al. The GABA transaminase, ABAT, is essential for mitochondrial nucleoside metabolism. Cell Metab 2015;21(3):417-27. PMID 25738457
- 07
- Bradbury AM, Bongarzone ER, Sands MS. Krabbe disease: New hope for an old disease. Neurosci Lett 2021;752:135841. PMID 33766733
- 08
- Feng Y, Wei ZH, Liu C, et al. Genetic variations in GABA metabolism and epilepsy. Seizure 2022;101:22-9. PMID 35850019
- 09
- Gao X, Jia X, Xu M, et al. Regulation of gamma-aminobutyric acid transaminase expression and its clinical significance in hepatocellular carcinoma. Front Oncol 2022;12:879810. PMID 35847853
- 10
- Gibson KM. Gamma-aminobutyric acid (GABA) transaminase deficiency. In: Buyse ML, editor. Birth defects encyclopedia. Cambridge (MA): Blackwell Scientific, 1990:766-7.
- 11
- Gibson KM, Nyhan W L, Jaeken J. Inborn errors of GABA metabolism. Bioessays 1986;4:24-7. PMID 3790108
- 12
- Gibson KM, Sweetman L, Nyhan WL, Jansen I, Jaeken J. Demonstration of 4-aminobutyric acid aminotransferase deficiency in lymphocytes and lymphoblasts. J Inherit Metab Dis 1985;8:204-8. PMID 3939544
- 13
- Gowda VK, Srinivasan VM. Rare cause of drug-resistant epilepsy due to GABA transaminase deficiency: A case report from India. Karnataka Paediatr J 2023;37(4):120-1.
- 14
- Grove J, Schechter PJ, Tell G, et al. Increased gamma-aminobutyric acid (GABA), homocarnosine and beta-alanine in cerebrospinal fluid of patients treated with gamma-vinyl GABA (4-amino-hex-5-enoic acid). Life Sci 1981;28:2431-9. PMID 6789022
- 15
- Hegde AU, Karnavat PK, Vyas R, DiBacco ML, Grant PE, Pearl PL. GABA transaminase deficiency with survival into adulthood. J Child Neurol 2019;34(4):216-20. PMID 30644311
- 16
- Ichikawa K, Tsuji M, Tsuyusaki Y, Tomiyasu M, Aida N, Goto T. Serial magnetic resonance imaging and 1H-magnetic resonance spectroscopy in GABA transaminase deficiency: a case report. JIMD Rep 2019;43:7-12. PMID 29478219
- 17
- Jaeken J. Disorders of neurotransmitters. In: Fernandes J, Saudubray JM, Tada K, editors. Inborn metabolic diseases: diagnosis and treatment. New York: Springer-Verlag, 1990:637-48.
- 18
- Jaeken J, Casaer P, de Cock P, et al. Gamma-aminobutyric acid-transaminase deficiency: a newly recognized inborn error of neurotransmitter metabolism. Neuropediatrics 1984;15:165-9. PMID 6148708
- 19
- Jaeken J, Casaer P, Haegele KD, Schechter PJ. Review: normal and abnormal central nervous system GABA metabolism in childhood. J Inherit Metab Dis 1990;13:793-801. PMID 2079831
- 20
- Jakobs C, Jaeken J, Gibson KM. Inherited disorders of GABA metabolism. J Inherit Metab Dis 1993;16:704-15. PMID 8412016
- 21
- Kennedy AD, Pappan KL, Donti T, et al. 2-Pyrrolidinone and succinimide as clinical screening biomarkers for GABA-transaminase deficiency: anti-seizure medications impact accurate diagnosis. Front Neurosci 2019;13:394. PMID 31133775
- 22
- Koenig MK, Bonnen PE. Metabolomics profile in ABAT deficiency pre- and post-treatment. JIMD Rep 2019;43:13-17. PMID 29480352
- 23
- Koenig MK, Hodgeman R, Riviello JJ, et al. Phenotype of GABA-transaminase deficiency. Neurology 2017;88(20):1919-24. PMID 28411234
- 24
- Louro P, Ramos L, Robalo C, et al. Phenotyping GABA transaminase deficiency: a case description and literature review. J Inherit Metab Dis 2016;39(5):743-7. PMID 27376954
- 25
- Lynch DS, Wade C, Paiva ARB, et al. Practical approach to the diagnosis of adult-onset leukodystrophies: an updated guide in the genomic era. J Neurol Neurosurg Psychiatry 2019;90(5):543-54. PMID 30467211
- 26
- Martirosian V, Deshpande K, Zhou H, et al. Medulloblastoma uses GABA transaminase to survive in the cerebrospinal fluid microenvironment and promote leptomeningeal dissemination. Cell Rep 2021;35(13):109302. PMID 34192534
- 27
- Medina-Kauwe LK, Nyhan WL, Gibson KM, Tobin AJ. Identification of a familial mutation associated with GABA-transaminase deficiency disease. Neurobiol Dis 1998;5(2):89-96. PMID 9746906
- 28
- Medina-Kauwe LK, Tobin AJ, De Meirleir L, et al. 4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency. J Inherit Metab Dis 1999;22:414-27. PMID 10407778
- 29
- Morales-Briceño H, Chang FCF, Wong C, et al. Paroxysmal dyskinesias with drowsiness and thalamic lesions in GABA transaminase deficiency. Neurology 2019;92(2):94-7. PMID 30617166
- 30
- Nagao T, Braga JD, Chen S, et al. Synergistic effects of peripheral GABA and GABA-transaminase inhibitory drugs on food intake control and weight loss in high-fat diet-induced obese mice. Front Pharmacol 2024;15:1487585. PMID 39415835
- 31
- Nagappa M, Bindu PS, Chiplunkar S, et al. Hypersomnolence-hyperkinetic movement disorder in a child with compound heterozygous mutation in 4-aminobutyrate aminotransferase (ABAT) gene. Brain Dev 2017;39(2):161-5. PMID 27596361
- 32
- Nutzenadel W. Disorders of beta-alanine, 4-aminobutyrate (GABA), carnosine, and homocarnosine. In: Fernandes J, Saudubray JM, Tada K, editors. Inborn metabolic diseases: diagnosis and treatment. New York: Springer-Verlag, 1990:337-43.
- 33
- Oshi A, Alfaifi A, Seidahmed MZ, et al. GABA transaminase deficiency. Case report and literature review. Clin Case Rep 2022;9(3):1295-8. PMID 33768830
- 34
- Parviz M, Vogel K, Gibson KM, Pearl PL. Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies. J Pediatr Epilepsy 2014;3(4):217-27. PMID 25485164
- 35
- Pearl PL, Parviz M, Vogel K, Schreiber J, Theodore WH, Gibson MK. Inherited disorders of gamma-aminobutyric acid metabolism and advances in ALDH5A1 mutation identification. Dev Med Child Neurol 2015;57(7):611-7. PMID 25558043
- 36
- Powers M. GABA supplementation and growth hormone response. Med Sport Sci 2013;59:36-46. PMID 23075553
- 37
- Racagni G, Apud JA, Cocchi D, Locatelli V, Muller EE. Minireview: GABAergic control of anterior pituitary hormone secretion. Life Sci 1982;31:823-38. PMID 6294431
- 38
- Scriver CR, Gibson KM. Disorders of beta- and gamma-amino acids in free and peptide-linked forms. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular basis of inherited disease. 7th ed. New York: McGraw-Hill, 1995.
- 39
- Scriver CR, Pueschel S, Davies E. Hyper-beta-alaninemia associated with beta-aminoaciduria and gamma-aminobutyric aciduria, somnolence and seizures. N Engl J Med 1966;274:635-43. PMID 17926374
- 40
- Sjaastad O, Berstad J, Gjesdahl P, Gjessing L. Homocarnosinosis. 2. A familial metabolic disorder associated with spastic paraplegia, progressive mental deficiency, and retinal pigmentation. Acta Neurol Scand 1976;53:275-90. PMID 1266573
- 41
- Sweetman F, Gibson KM, Sweetman L, et al. Activity of biotin-dependent and GABA metabolizing enzymes in chorionic villus samples: potential for 1st trimester prenatal diagnosis. Prenat Diagn 1986;6:187-94. PMID 3725738
- 42
- Thistlewaite LR, Li X, Burrage LC, et al. Clinical diagnosis of metabolic disorders using untargeted metabolomic profiling and disease-specific networks learned from profiling data. Sci Rep 2022;12(1):6556. PMID 35449147
- 43
- Tsuji M, Aida N, Obata T, et al. A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy. J Inherit Metab Dis 2010;33(1):85-90. PMID 20052547
- 44
- Yasir M, Park J, Han ET, et al. Computational exploration of the effects of mutations on GABA aminotransferase in GABA aminotransferase deficiency. Int J Mol Sci 2023;24(13):10933. PMID 37446113
- 45
- Zheng Q, Bi R, Xu M, et al. Exploring the genetic association of the ABAT gene with Alzheimer’s disease. Mol Neurobiol 2021;58(5):1894-903. PMID 33404980
Contributors
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Authors
-
Swann Li
Ms. Li of Georgetown University has no relevant financial relationships to disclose.
See Profile -
Itay Tokatly Latzer MD
Dr. Tokatly Latzer of Boston Children's Hospital has no relevant financial relationships to disclose.
See Profile -
Phillip L Pearl MD
Dr. Pearl of Boston Children's Hospital and Harvard Medical School has no relevant financial relationships to disclose.
See Profile
Editor
-
Deepa S Rajan MD
Dr. Rajan of UPMC Children's Hospital of Pittsburgh has no relevant financial relationships to disclose.
See Profile
Former Authors
- Susan Combs BA
- Mahsa Parviz MD PhD
- Ryan Hodgeman BS
- Melissa L DiBacco MD
- Jasmine Gite BS
- K Michael Gibson PhD
- Jennifer Friedman MD
Patient Profile
- Age range of presentation
-
- 0 to 7 months
- Sex preponderance
-
- male=female
- Heredity
-
- heredity typical
- heredity may be a factor
- autosomal recessive
- Population groups selectively affected
-
- none selectively affected
- Occupation groups selectively affected
-
- none selectively affected
ICD & OMIM codes
- ICD-10
-
- Disorder of amino-acid metabolism, unspecified: E72.9
- ICD-11
-
- Inborn errors of amino acid or other organic acid metabolism: 5C50
- OMIM
-
- GABA-transaminase deficiency: #613163
This is an article preview.
Start a Free Account
to access the full version.
-
Nearly 3,000 illustrations, including video clips of neurologic disorders.
-
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
-
Full spectrum of neurology in 1,200 comprehensive articles.
-
Listen to MedLink on the go with Audio versions of each article.
Questions or Comment?
MedLink, LLC
3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122
Toll Free (U.S. + Canada): 800-452-2400
US Number: +1-619-640-4660
Support: service@medlink.com
Editor: editor@medlink.com
ISSN: 2831-9125
Also in This Category
-
-
Neurogenetic Disorders
GM2 gangliosidoses
Apr. 30, 2026
-
Neuropharmacology & Neurotherapeutics
Levacetylleucine
Apr. 23, 2026
-
Neurogenetic Disorders
HHH syndrome
Apr. 14, 2026
-
Neurogenetic Disorders
Hyperargininemia
Apr. 14, 2026
-
Neurogenetic Disorders
Carbamoyl phosphate synthetase 1 deficiency
Apr. 14, 2026
-
Neurogenetic Disorders
Ornithine transcarbamylase deficiency
Apr. 14, 2026
-
Neurogenetic Disorders
Citrullinemias types 1 and 2
Apr. 14, 2026