Methylmalonic acidemia is an autosomal recessive disorder, caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase, a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin, or deficiency of the enzyme methylmalonyl-CoA epimerase. Onset of the manifestations usually is in early infancy, and varies from mild to life threatening. These manifestations include: lethargy, failure to thrive, recurrent vomiting, dehydration, respiratory distress, muscle hypotonia, hepatomegaly, and coma. Patients may also show signs of anemia (not megaloblastic), have potentially life-threatening ketoacidosis and/or hyperammonemia, and developmental delay and intellectual deficit, with metabolic stroke affecting the brain stem.
The cblC type methylmalonic acidemia with homocystinuria is the most frequent type of methylmalonic acidemia with homocystinuria. To date over 500 cases of this condition have been reported. The diagnosis is based on clinical, biochemical, complementation group, and molecular genetic data. Treatment of the thromboembolic complications may include initiation of hydroxocobalamin (OHCbl) and betaine. Long-term management focuses on improving the metabolic derangement by lowering plasma tHcy and MMA concentrations and maintaining plasma methionine concentrations within the normal range.
In a retrospective analysis of IEMs diagnosed over a 12-year period (1998-2010) in a hospital in Lebanon, Karam et al. (2013) found 11 patients diagnosed with cobalamin c deficiency. The median age of diagnosis was 3-months.
Al-Shamsi et al. (2014) undertook a study to calculate the birth prevalence of IEMs among Emiratis in the UAE by taking into consideration all neonates born with an inherited metabolic condition at Tawam Hospital between 1995 and 2012. A total of 37 distinct IEMs were found in Emirati neonates in this study, providing an estimated IEM birth prevalence of 75.24 per 100,000 live births. Cobalamin C Deficiency was found to have a birth prevalence of less than 0.98 per 100,000. A single mutation in the MMACHC gene was identified in the affected patient(s).