Phenotypes and genotypes of 126 patients with isolated methylmalonic aciduria

Objective To investigate the clinical, biochemical and genetic findings in patients with isolated methylmalonic aciduria. Methods From January 2001 to December 2014, a total of 126 patients with isolated methylmalonic aciduria from Peking University First Hospital were enrolled in this study.In 60 patients, gene analysis was performed.The clinical characteristics, laboratory findings, treatment and outcomes were retrospectively analyzed. Results Among the 126 patients, only 3 cases(2.4%) were detected through newborn screening and treated with dietary intervention, cobalamin and L-camitine.The age at onset of 123 cases(97.6%) varied from a few hours after birth to 7 years and 11 months old.The common presentations were recurrent vomiting, mental retardation, poor feeding, lethargy, respiratory distress, coma, seizures, cutaneous lesion and jaundice with 11 patients(8.73%) dead.Abnormal family history was found in 27(21.4%) patients.Metabolic acidosis and anemia were frequent laboratory findings.Basal ganglia damage and white matter changes were observed in most patients.Sixty patients got genetic analysis, and 58 cases of them had MUT gene mutations.One case had MMAA defect.One case had MMAB defect.In MUT gene, 12 novel mutations were identified.After treatment, mild to severe psychomotor retardation was observed in 112 patients with isolated methylmalonic aciduria. Conclusions The clinical manifestation of patients with isolated methylmalonic aciduria is complex, and prone to appear metabolic crisis.MUT defect is the main cause.Early metabolic investigation is very important to reach diagnosis.Newborn screening, early diagnosis and adequate therapy are key points to reduce the morta-lity and handicap. Key words: Organic aciduria; Methylmalonic aciduria; MUT; MMAA; MMAB; Inherited metabolic disease