Isolated 3-methylcrotonyl-coenzyme A carboxylase deficiency is a rare metabolic disorder inherited as an autosomal recessive trait [1]. We report features of patient with asymptomatic 3-methylcrotonyl-coenzyme A carboxylase deficiency and two novel heterozygous MCCC1 mutations.

The proband, a girl, was born in the 41th week of gestation with a weight of 2.85 kg to non-consanguineous parents. On the fourth day of life, tandem mass spectrometry was performed, revealing that the level of 3-hydroxyisovaleryl-carnitine (C5-OH) was high (2.74 µM; reference range <0.6 µM). C5-OH levels were repeated in dried blood spot, and it was again high (3.23 ìM). Due to persistently elevated level of C5-OH, blood samples from the proband, her parents and her elder brother were tested for genetic- and mutation- analysis, after informed consent. Genetic analysis of the proband showed two heterozygous novel missense mutations (MCCC1 NW_020166.3: c.1570G>C (p.D524H) and MCCC1 NW_020166.3: c.601C>T (p.P201S)) in the MCCC1 gene. The father was heterozygous for c.601C>T (p.P201S) and the mother was heterozygous for c.1570G>C (p.D524H). The elder brother was heterozygous for c.601C>T (p.P201S). At 11 months of age, the proband was still asymptomatic, and with normal growth and development.

In general, most newborns with isolated 3-methylcrotonyl-coenzyme A carboxylase deficiency detected on screening appear clinically normal and healthy. Features such as vomiting, ketosis, poor oral intake, irritability, lethargy and hypotonia are reported in up to 15% of patients; majority (92.5%) of infants show completely appropriate age-matched development [2].

Acknowledgment: Dr Yang Zou.

Funding: The key research and development program of JiangXi Province (20171BBG70106). Competing interests: None stated.

1. Arnold GL, Koeberl DD,　Matern D, Barshop B, Braverman N, Burton B, et al. A Delphi-based　consensus　clinical practice　protocol　for the diagnosis and management　of 3-methylcrotonyl CoA carboxylase deficiency. Mol Genet Metab.　2008;93:363-70.

2. Lam C, Carter JM, Cederbaum SD, Neidich J, Gallant NM,　Lorey F,　et al. Analysis of cases of 3-methylcrotonyl CoA carboxylase deficiency (3-MCCD) in the California newborn screening program reported in the state database. Mol Genet Metab.　 2013;110:477-83.