Outcome of individuals with low-moderate methylmalonic aciduria detected through a neonatal screening program

Background: The clinical spectrum of methylmalonic aciduria (MMAuria) ranges from severe, neonatal acidosis to benign asymptomatic organic aciduria. In 1975, screening for MMAuria was established in the province of Quebec. Although newborn screening programs facilitate presymptomatic detection and treatment and also detect asymptomatic variants, uncertainties about potential long-term hazards of mild to moderate elevations of MMA create concern. The objective of this study was to examine the outcome of individuals excreting low to intermediate quantities of MMA, ascertained by a newborn screening program. Results and study design: One hundred and thirty-six individuals with elevations of urinary MMA were initially identified by the screening program; 122 individuals were noted to have excretion of urinary MMA <1400 mu mol/mmol creatinine. At follow-up assessment at 1 year of age, in 65 of these 122 individuals, the MMA excretion had resolved. Of the remaining individuals, 9 were lost to follow-up, 13 had symptoms, and the remaining 35 were free of symptoms. Among the 35 individuals with asymptomatic persistent MMAuria, MMA excretion has resolved in 13 over 1 year; 22 individuals exhibit persistent low-moderate MMAuria (range, 210 to 1133 mu mol/mmol creatinine). Conclusion: Follow-up examination of individuals in the latter asymptomatic cohort with persistent low-moderate MMAuria indicates normal somatic and cognitive outcomes.