Fact-sheet: Methylmalonic acidemia
Updated on 09/27/2019 at 8:52 AM
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Definition
Methylmalonic acidemias are a group of genetically and biochemically heterogeneous, rare disorders (1/25,000 to 1/50,000).
Common feature: abnormal accumulation of methylmalonic acid (MMA) in tissues and body fluids, transmitted in an autosomal recessive manner.
Among the most common causes are methylmalonyl-CoA mutase deficiency (50-70%) and isolated adenosylcobalamin deficiency, a B12-derived coenzyme (30%). There are numerous other causes: see classification.
Clinical features
Clinical presentation is highly variable depending on the type of methylmalonic acidemia: neonatal forms, later-onset forms, acute decompensations...
MRI
- Basal ganglia necrosis ++
- Stroke
- Cerebral atrophy
Classification
Non-hereditary causes of elevated MMA:
- Nutritional deficiency++ (B12-deficient mother, vegan diet)
Hereditary causes of elevated MMA:
- Methylmalonyl-CoA mutase enzyme deficiency: complete deficiency mut0 (B12-unresponsive methylmalonic acidemia) or incomplete mut-
- Methylmalonyl-CoA epimerase deficiency (mild MMA excretion)
- Cobalamin (B12) absorption and transport abnormalities: congenital intrinsic factor deficiency, enterocyte transport deficiency (Imerslund-Grasbeck syndrome), transcobalamin deficiency
- Intracellular cobalamin metabolism abnormalities: isolated adenosylcobalamin deficiency (B12-responsive methylmalonic acidemia without homocystinuria): classes cbIA, cbIB, CbIDv2; combined adenosylcobalamin and methylcobalamin deficiency (methylmalonic acidemia with homocystinuria, MAH): classes cbIC, cbID, cbIF, cbIJ
- Succinyl-CoA ligase deficiency (SUCLG1 or SUCLA2 deficiency) (mild MMA excretion)
