The reference OMIM entry for this protein is 248360

Malonyl-coa decarboxylase deficiency

A number sign (#) is used with this entry because the disorder is caused by mutation in the malonyl-CoA decarboxylase gene (MLYCD; 606761), which maps to chromosome 16q.

DESCRIPTION

Malonyl-CoA decarboxylase deficiency is an uncommon inherited metabolic disease. The characteristic phenotype is variable, but may include developmental delay in early childhood, seizures, hypotonia, diarrhea, vomiting, metabolic acidosis, hypoglycemia, ketosis, abnormal urinary compounds, lactic acidemia, and hypertrophic cardiomyopathy (Sweetman and Williams, 2001).

CLINICAL FEATURES

Brown et al. (1984) described deficiency of malonyl-CoA decarboxylase in a 5-year-old boy who had been studied for short stature, abdominal pain, chronic constipation, episodic vomiting, and metabolic acidosis. Abnormal amounts of malonic, methylmalonic, and succinic acids were found in his urine. The parents were first cousins, and a sib had died at 3.5 months of age. The mitochondrial malonyl-CoA decarboxylase was very deficient and both parents had an intermediate level of activity. Haan et al. (1986) reported a second boy with more severe malonyl-CoA decarboxylase deficiency who presented in a quite different way from the previous patient and whose urine contained, in addition to the above-mentioned organic acids, adipic, glutaric, and suberic acids. The child was mildly mentally retarded and presented with vomiting, seizures, hypoglycemia, and mild metabolic acidosis during a urinary tract infection. Mitochondrial malonyl-CoA decarboxylase activity in fibroblasts was 4% of normal; in both parents it was about half normal. MacPhee et al. (1993) described 2 patients, a son of second-cousin Irish parents and a girl, the daughter of first-cousin Scottish parents. They were investigated during episodes of vomiting and febrile convulsions associated with concomitant developmental delay. Malonicaciduria and grossly reduced malonyl-CoA decarboxylase activity were demonstrated. FitzPatrick et al. (1999) provided an analysis of the 7 reported cases of MCD deficiency. The condition was present in early childhood and was associated with malonicaciduria (7 of 7), methylmalonicaciduria (7 of 7), developmental delay (7 of 7), seizure disorder (4 of 7), hypoglycemia (4 of 7), and cardiomyopathy (2 of 7). De Wit et al. (2006) reported a 4.5-year-old girl, born of consanguineous Moroccan parents, with MCD deficiency. Family history revealed 2 neonatal deaths and several miscarriages. The patient had feeding problems, failure to thrive, and severe developmental delay with no language development. Diagnosis occurred at age 2 years when metabolic screening showed compensated metabolic acidosis, hyperammonemia, increased malonic acid, and other abnormalities. Skin fibroblasts showed complete MCD deficiency. Cardiac exam was normal. The patient also had a very poor appetite. Brain MRI showed generalized atrophy, major white matter loss, thickened cortex with pachygyria, and periventricular nodular heterotopia. These findings were consistent with a malformation of cortical development. A review of the literature found that some previously reported patients also had brain imaging abnormalities, such as frontotemporal atrophy and white matter changes.

INHERITANCE

The cases reported by Brown et al. (1984), Haan et al. (1986), and MacPhee et al. (1993) supported autosomal recessive inheritance.

CLINICAL MANAGEMENT

Haan et al. (1986) showed in one case that ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 248360 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).