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

Abstract

JGM 3-methylcrotonyl-CoA accumulates and is eventually converted into 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, which are typically elevated in this disease. MCCC2 mutations were reported to be 1.7 times more common than MCCC1 mutations, as found in a cohort study of 53 newborns [3]. Of the genetic mutations reported in Korean patients, 75% have been found within MCCC2 [4,5]. Infants carrying a mutation identified by neonatal screening usually appear to be asymptomatic and remain healthy. However, some patients are reported to present with hypotonia, encephalopathy, seizure, failure to thrive, cardiomyopathy, and late onset severe metabolic decompensation with metabolic acidosis and hypoglycemia [1,[6][7][8][9].In this report, we present the clinical characteristics, laboratory findings and molecular analysis of a patient possessing novel heterozygous mutations of MCCC1.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.

Discovery, Structure, and Function of Filamentous 3-Methylcrotonyl-CoA Carboxylase

“…In humans, upregulated MCC expression often correlates with various cancers (Chen et al, 2021; Dai et al, 2020; Gondáš et al, 2022; He et al, 2020; Liu et al, 2019). On the other hand, MCC deficiency, one of the most common metabolic disorders in newborns (Lee and Hong, 2014), may cause vomiting, seizures, and other neurological abnormalities (Grünert et al, 2012; Kim et al, 2017).…”

Discovery, Structure, and Function of Filamentous 3-Methylcrotonyl-CoA Carboxylase

“…In humans, upregulated MCC expression often correlates with various cancers 4,[13][14][15][16] . On the other hand, MCC deficiency, one of the most common metabolic disorders in newborns 17 , may cause vomiting, seizures, and other neurological abnormalities 18,19 .…”