Newborn screening and early biochemical follow-up in combined methylmalonic aciduria and homocystinuria cblC type and utility of methionine as a secondary screening analyte

摘要

IntroductionCombined methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, is an inherited disorder of vitamin B12 metabolism caused by mutations in MMACHC. CblC typically presents in the neonatal period with neurological deterioration, failure to thrive, cytopenias, and multisystem pathology including renal and hepatic dysfunction. Rarely, affected individuals present in adulthood with gait ataxia and cognitive decline. Treatment with hydroxycobalamin may ameliorate the clinical features of early-onset disease and prevent clinical late-onset disease. Propionic acidemia (PA), methylmalonic acidemia (MMA), and various disorders of cobalamin metabolism are characterized by elevated propionylcarnitine (C3) on Newborn Screening (NBS). Distinctions can be made between these disorders with secondary analyte testing. Elevated methionine is already routinely used as a NBS marker for cystathionine ß-synthase deficiency. We propose that low methionine may be useful as a secondary analyte for specific detection of cbl disorders among a larger pool of infants with elevated C3 on NBS.