Clinical Manifestations, Gene Analysis of Patients with 3-Methylcrotonyl-CoA Carboxylase Deficiency

OBJECTIVE: 3-Methylcrotonyl CoA carboxylase deficiency (3MCCD) is classified as organic acid disease due to leucine catabolism. It is among the most common inborn errors of metabolism identified on newborn screening test using tandem mass spectrometry. There is a broad spectrum of clinical presentations. 3-Methylcrotonyl CoA carboxylase converts 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA using biotin as a coenzyme in mitochondria. Restricting protein diets and supplementing carnitine, glycine, and biotin are known treatments. We reported this study to find out clinical symptoms, type of gene mutation, and effect of treatment. METHODS: This study was based on retrospective data of patients with 3MCCD in Soonchunhyang University Seoul Hospital and Soonchunhyang University Bucheon Hospital between April 2009 to August 2016. RESULTS: All 10 infants were born term infants and had no symptoms. During the neonatal period, abnormalities were detected in the new born screening test using tandem mass spectrometry, 3-hydroxyisovalerylcarnitine was increased. 3-Methylcrotonylglycine (3MCG) and 3-hydroxyisovalreric acid (3HIVA) were examined in urine organic acid assay. The results showed that 3MCG was increased in all 10 children. Except for three of the 10 children, 3HIVA was increased. Genetic tests were performed on all 10 children. MCCC1 gene mutations were detected in four patients and MCCC2 mutations were detected in six patients. After diagnosis, all children were recommended leucine-restricted diets, and seven of the 10 patients started to feed on leucine free formula for the treatment of 3MCCD. CONCLUSION: According to our data, all patients has no symptoms and are shown normal development. There were no clinical symptoms or changes in prognosis according to gene mutation type.

Novel heterozygous MCCC1 mutations identified in a patient with 3-methylcrotonyl-coenzyme A carboxylase deficiency

Isolated 3-methylcrotonyl-CoA carboxylase deficiency is an autosomal recessive disorder affecting leucine metabolism; it is one of the most common inborn metabolic diseases detected in newborn screening. Mutations in the genes MCCC1 or MCCC2 cause a defect in the enzyme 3-methylcrotonyl-CoA carboxylase, with MCCC2 mutations being the form predominantly reported in Korea. The majority of infants identified by neonatal screening usually appear to be asymptomatic and remain healthy; however, some patients have been reported to exhibit mild to severe metabolic decompensation and neurologic manifestations. Here we report the clinical features of a patient with asymptomatic 3-methylcrotonyl-CoA carboxylase deficiency and novel heterozygous MCCC1 mutations.

Identification of a Novel Mutation in the MCCC2 Gene of a Korean Patient with 3-Methylcrotonyl-CoA Carboxylase Deficiency

3-methylcrotonyl-CoA carboxylase deficiency is an autosomal recessive disorder characterized by a defect in leucine catabolism. We report the case of an 80-day-old patient with 3-methylcrotonyl-CoA carboxylase deficiency who had elevated levels of 3-hydroxyisovalerylcarnitine (45.56 micromol/L; reference range, C (p.Gly105Arg)] at nucleotide position 313 and a mutation caused by a heterozygous A to T transversion [c.1252A>T (p.lle418Phe)] at nucleotide position 1252. Identification of these 2 novel MCCC2 gene mutations in our patient suggested that analysis of the MCCC1 and MCCC2 genes might prove useful in the diagnosis of 3-methylcrotonyl-CoA carboxylase deficiency.

A Case of Lennox-Gastaut Syndrome due to 3-Methylcrotonyl CoA Carboxylase Deficiency

3-Methylcrotonyl-CoA carboxylase(MCC) is a biotin-dependent enzyme involved in the leucine metabolism. We describe a patient with MCC deficiency who manifested with Reye syndrome-like illness with status epilepticus, metabolic acidosis, hypoglycemia, hyperammonemia, elevated liver enzymes and neurologic impairments after a viral gastroenteritis and then suffered from Lennox-Gastaut syndrome. Urinary organic acid analysis revealed increased excretions of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. This patient was managed with a leucine restriction diet and supplementation of biotin and carnitine, which was not so effective. He suffered from neurologic sequelae such as Lennox-Gastaut syndrome, motor and cognitive impairements.