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Methylmalonicaciduria with homocystinuria is a metabolic disorder consisting of an impaired vitamin B12 metabolism. The combination of abnormal excretion of methylmalonic acid and derived components, increased total or free plasmatic homocystine (> 100 micromo/L), and normal to low plasmatic methionine is strongly suggestive of impaired absorbtion, transportation, binding, or intracellular metabolism of vitamin B12. Methylcobalamin, one of vitamin B12`s derived products, acts, as cofactor to homocystine methyltransferase, while adenosyl cobalamin, another derived product, is a cofactor of methylmalonic CoA mutase. Apart from transcolabamine II deficiencies, three genetic deficiencies have been identified by cellular complementation: the CBLC and CBLD group that may be involved in defective cytoplasmic cobalamin reductase, and the CBLF group causing impaired transportation of cobalamin bound to transcobalamin II out of lysosomes. CBLC is the only frequent disorder of the three. Several clinical forms have been described: an infantile form with acidotic coma, hypotonia, microcephaly, convulsions, megaloblastic anemia, and leukopenia; another more severe infantile form with multiorgan failure, myocardiopathy, retinopathy, and hemolytic uremic syndrome; and finally a juvenile form with onset during childhood or adolescence that causes psychiatric disorders or subacute combined spine degeneration. Chromatography of organic acids and aminoacids is suggestive of the disease, but diagnosis is confirmed by studying complementation groups of cobalamin in fibroblasts. Patients are treated with intramuscular injections of hydroxocobalamin, oral betaine, and folic acid. Antenatal diagnosis is feasible. |