Methylmalonic aciduria type cblA
Aciduria, as well known as methylmalonic academia, is a congenital error in the metabolism of vitamin B12, characterized by gastrointestinal and neurometabolic symptoms which are caused by a decrease in function of the mitochondrial enzyme methylmalonyl-CoA mutase.
The prevalence is 1/48-61,000 in North America, and 1/26,000 in China.
Clinical symptoms include lethargy, growth retardation, recurrent vomiting, dehydration, respiratory failure and muscular hypotonia, as well as developmental delay, intellectual deficit, hepatomegaly and coma. The long-term consequences of this disorder include neurological damage and terminal renal failure.
Patients may respond or not to the vitamin B12 treatment.
Vitamin B12-sensitive methylmalonic acidemia is caused by defects in the synthesis of adenosylcobalamin (AdoCbl) resulting from genetic alterations in cobalamin metabolism (cblA, cblB or cblD variant 2 [cblDv2]).
Vitamin B12-resistant methylmalonic acidemia is causedby a complete (mut0) or partial (mut-) deficit in the activity of the mitochondrial enzyme methylmalonyl-Coa mutase.
CblA is caused by mutations in the MMAA gene (4q31.1-2), cblB by mutations in the MMAB gene (12q24.1), cblDv2 by mutations in the MMADHC gene (2q23.2), and mut0 and mut – by mutations in the MUT gene (6p21); all of them are inherited following an autosomal recessive pattern. The disorder described in the past as cblH is currently classified as cblDv2.
GENE OR REGION STUDIED