3-methylcrotonyl-CoA carboxylase deficiency in a child with developmental regression and delay: call for early diagnosis and multidisciplinary approach.

3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency (3-MCC-D) is an autosomal recessive disorder with a variable phenotype. Reduced 3-MCC enzyme activity results in impaired leucine metabolism causing, for example, metabolic acidosis, ketotic hypoglycaemia and carnitine deficiency. The spectrum of clinical presentation is wide, ranging from severe early-onset presentations to incidental findings in asymptomatic individuals. This report describes the case of a young girl who underwent dramatic developmental regression at 11 months of age, following a respiratory tract infection. Metabolic investigations revealed high excretions of urinary 3-methylcrotonylglycine and 3-hydroxyisovaleric acid, consistent with 3-MCC-D. Treatment was commenced immediately, including carnitine, biotin and moderate dietetic modifications. Molecular genetic investigations confirmed compound heterozygosity for two pathogenic variants in the MCCC1 gene, Trp358Cysfs*13 and duplication of exons 2 and 3. Now in middle childhood, the girl is meeting all her developmental milestones and has had no metabolic decompensation in 6 years of follow-up.