Clinical and Molecular Spectrum of Patients with Methylmalonic Acidemia.

OBJECTIVES

To study the clinical and molecular spectrum of Methylmalonic acidemia (MMA).

METHODS

In this retrospective study, the records of 30 MMA patients were evaluated for their phenotype, biochemical abnormalities, genotype, and outcomes.

RESULTS

Thirty patients with MMA (age range 0-21 y) from 27 unrelated families were enrolled. Family history and consanguinity were noted in 10/27 (37%) and 11/27 (41%) families respectively. Acute metabolic decompensation was more common (57%) than chronic presentation. Biochemical work-up was suggestive of isolated MMA (n = 18) and MMA with homocystinuria (n = 9) respectively. Molecular testing in 24 families showed 21 pathogenic or likely pathogenic variants with MMA cblC as the commonest molecular subtype (n = 8). B12 responsiveness, an important determinant of long-term outcome, was observed in eight patients [MMAA (n = 3) and MMACHC (n = 5)]. Mortality was 30% (n = 9/30) with a high proportion of early-onset severe disease and fatal outcome in isolated MMA mut (4/4) and MMA cblB (3/3), as compared to MMA cblA (1/5) and MMA cblC (1/10).

CONCLUSIONS

This study cohort had MMA cblC subtype as the most common type of MMA followed by the MMA mutase defect. Outcomes in MMA are influenced by the type of molecular defect, age, and severity of presentation. Early detection and management is likely to result in better outcomes.