Methylmalonic acidemia (MMA) is an inborn error of metabolism presenting in neonates or infants as acute failure of liver, renal and CNS functions. The aim of study was a description of clinical course, metabolic findings and molecular cause of this disease at 10 patients with MMA who were diagnosed within selective screening of inherited metabolic diseases between 1988 and 2005. Seven patients presented in neonatal period with fast progressive coma accompanied by metabolic acidosis. Three patients presented in infancy with failure to thrive and repeated attacks of vomiting. Laboratory investigations revealed at all patients mild to marked hyperammonemia, ketoacidosis, markedly increased concentration of methylmalonic acid in blood and elevated excretion of methylmalonic acid, 3-hydroxypropionic acid, methylcitric acid and propionylglycine in urine. Performed enzyme assays demonstrated deficiency of activity of methylmalonyl- CoA mutase in 5 children (mut form) and molecular biological analyses detected mutations present in MUT gene coding methylmalonyl-CoA mutase, MMAA gene coding protein with still unclear function and MMAB gene coding enzyme cob(I)adenosyltransferase. The error of metabolism of adenosylcobalamine (cbl form) was demonstrated in 4 patients with normal activity of methylmalonyl-CoA mutase – 2 children were identified as cblA and 2 children as cblB. Prognosis of patients with MMA is not favourable. The most serious course of disease was present at patients with mut form, 4 of 5 died. The patients with cblA form had much milder clinical symptoms, only they were responsive to vitamin B12, while other patients with MMA were/are non-responsive to B12 supplementation. On the basis of this study the efficient genetic counselling and prenatal diagnostics can be offered to the affected families, which were not available before.

        Key words: methylmalonic acidemia, methylmalonyl-CoA mutase, cobalamine deficiency, methylmalonic acid, gas chromatography/mass spectrometry, tandem mass spectrometry