The first case of 3-methylcrotonyl-CoA carboxylase (MCC) deficiency responsive to biotin.

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Friebel D, von der Hagen M, Baumgartner ER, Fowler B, Hahn G, Feyh P, Heubner G, Baumgartner MR, Hoffmann GF

The first case of 3-methylcrotonyl-CoA carboxylase (MCC) deficiency responsive to biotin.

Neuropediatrics. 2006 Apr;37(2):72-8.

PubMed ID

16773504 [ View in PubMed

]

Abstract

3-Methylcrotonylglycinuria is an inborn error of leucine catabolism with an autosomal recessive pattern of inheritance that results from a deficiency of 3-methylcrotonyl-CoA carboxylase (MCC). We report on a nine-year-old boy with severe psychomotor retardation who developed infantile spasms at the age of three weeks. Urine analysis at the age of two years revealed massive 3-methylcrotonylglycinuria and 3-hydroxyisovaleric aciduria suggesting MCC deficiency. Carnitine serum levels were decreased. Biotin therapy led to a dramatic decrease in the frequency of seizures, disappearance of hypsarrhythmia, and near normalisation of organic aciduria. Four months later a protein-restricted diet was introduced in addition and the boy remained clinically and metabolically stable. However, severe psychomotor delay persisted, and the seizures partially reoccurred. Biochemical findings showed partial MCC deficiency in cultured fibroblasts. Molecular genetic studies revealed a heterozygote missense mutation, MCCA-R385S, converting arginine to serine in a highly conserved region of the MCCA gene. This is the first patient with MCC deficiency caused by a heterozygote mutation and who demonstrated a substantial and sustained clinical and biochemical response to therapeutic doses of biotin. Sadly, this patient again also demonstrates that the main determinant of the outcome of even easily treatable metabolic diseases is timely diagnosis.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Biotin	Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial	Protein	Humans	Unknown	Cofactor	Details