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  • Updated 11.30.2023
  • Released 02.07.1994
  • Expires For CME 11.30.2026

Isolated beta-methylcrotonyl-CoA carboxylase deficiency



The author explains that based on the results of newborn screening, confirmed individuals with isolated beta-methylcrotonyl-CoA carboxylase deficiency often have mild biochemical phenotypes. When neonates are found with elevated C5-OH metabolites on newborn screening and only a single mutation in the carboxylase genes is identified, their mothers should be tested to exclude the possibility that they have isolated beta-methylcrotonyl-CoA carboxylase deficiency.

Key points

• Beta-methylcrotonyl-CoA carboxylase deficiency, an inherited metabolic disorder, usually presents during early childhood with neurologic symptoms, metabolic acidosis, and organic aciduria.

• Some individuals with beta-methylcrotonyl-CoA carboxylase deficiency can exhibit mild symptoms, whereas others have severe symptoms.

• Children with beta-methylcrotonyl-CoA carboxylase deficiency can be identified by tandem mass spectroscopy on newborn screening, or they may be identified later by the characteristic organic aciduria when they are symptomatic.

• Although beta-methylcrotonyl-CoA carboxylase is a biotin-dependent enzyme, individuals with the disorder do not usually respond to biotin therapy.

• Individuals with beta-methylcrotonyl-CoA carboxylase deficiency are usually treated with a low-protein or leucine-restricted, high-carbohydrate diet and carnitine supplementation.

Historical note and terminology

In the early 1970s, two children were described with beta-methylcrotonyl-glycinuria (18; 28; 29). These children had slightly different symptoms but could be differentiated by their responses to biotin supplementation. One improved markedly with biotin treatment (28; 29), whereas the other did not and was considered biotin-resistant (18; 59). Both were thought or shown to have beta-methylcrotonyl-CoA carboxylase deficiency (62). Other patients with beta-methylcrotonyl-glycinuria were subsequently reported, and almost all were biotin-responsive. These biotin-responsive patients were subsequently shown to have metabolites consistent with deficiencies of all three of the mitochondrial carboxylases; this was confirmed enzymatically in most of these children. They were designated as having multiple carboxylase deficiency (61; 72). Few of the children with beta-methylcrotonyl-glycinuria were shown to have beta-methylcrotonyl-CoA carboxylase deficiency with the normal activities of the other mitochondrial carboxylases. They were considered to have isolated beta-methylcrotonyl-CoA carboxylase deficiency. Since then, about a dozen children with isolated beta-methylcrotonyl-CoA carboxylase deficiency with a variety of clinical features have been reported. All have failed to respond to biotin therapy.

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