Methylmalonic acidemia (MMA)
Incidence
1/48.000-1/61.000. 10-15% of all organic acidurias. At least 4 different genotypes exist. All 5 enzymes of the urea cycle are depressed, with resultant hyperammonemia. Aut. recessive. Depr.gluconeogen. lead to hypoglyc. and increase ketone production.
Clinical Characteristics
Similar to Propionic acidemia (interm.vomiting, lethargy & ketosis). Prodromal phase of vomiting, fasting, rapidly lead to lethargy and coma with ketolactic acidosis. This can occur at any age, mostly early infancy. Vomit x sev days precede metab attacks The disease is transmitted as an autosomal recessive trait and is due to methylmalonyl-CoA-mutase deficiency, an enzyme that is common to the catabolism of valine, isoleucine, methionine, and threonine. Methylmalonyl-CoA-mutase transforms methylmalonate into succinate. Onset is usually infantile with ketoacidotic coma, dehydration, hyperammonemia, and leucothrombocytopenia. A subacute form begins during early childhood with vomiting, hypotonia, growth and psychomotor retardation. Finally there is a later form characterized by recurrent ketoacidotic comas. Complications include growth and psychomotor retardation, glomerulointerstitial nephropathy, and acute central grey nuclei disorders causing extrapyramidal signs. Chromatography of organic acids and aminoacids is suggestive, but diagnosis is confirmed by measuring the enzyme in fibroblasts. Patients should follow a strict, lifelong diet with limited protein intake. Treatment otherwise includes carnitine and antibiotics to destroy intestinal bacteria that produce propionic acid.
Precipitants
Heavy protein feeding, any infection. The best precipitants are fasting & vomiting
Provocation Tests
Methylmalonic acidemia: At present, no provocation test is adviced. Tandem MS and GC/MS provide always conclusive results.
Diagnostic Procedures
Methylmalonic acidemia:Tandem MS (acyl-carnitine profile in blood), GC/MS in urine. EB-F, OB-F, CB-F. Also see cobalamine mutations.