Long-term outcome in methylmalonic aciduria: A series of 30 French patients

ObjectiveTo better delineate the natural history of patients with methylmalonic aciduria (MMA).Study designThirty patients with vitamin-B12-unresponsive MMA (25 aged 1.5 to 22.0 years (y) at the end of the study and 5 who died during a metabolic crisis) were managed following standardized guidelines and studied retrospectively. The median follow-up was 8.3 y (range: 1.4–19.5). Patients were investigated with neuropsychological testing, brain MRIs, inulin clearances, biochemical and genetic studies.ResultsFifteen patients had a neonatal onset. Thirteen patients (43%) had significant neurological impairment. Chronic renal disease (CRD) occurred in 14 patients (47%) with a median age of onset of 6.5 y (range 1.5–18.6). Renal function further deteriorated in 4 patients within a median period of 5.8 y (range 2–7.4). Of 25 patients investigated at the enzymatic level, 17 were classified mut°, 3 mut- and 5 cblA. Mortality, number of acute decompensations (p = 0.031), median MMA urinary excretion (p = 0.006) and neurological impairment (p < 0.0001) were higher in mut° patients compared to mut-/cblA patients. Concerning the CRD, no difference incidence was found although the onset of CRD occurred earlier in mut° patients and was more severe.ConclusionsOur study provides unique data concerning the progression of renal disease in MMA. Patients with mut° phenotype have a more severe phenotype and probably an earlier and more severe CRD than patients with mut-/cblA phenotype.