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Published on: December 20, 2010
Clinical and Molecular Spectrum of Patients with Methylmalonic Acidemia
Neerja Gupta1, Mounika Endrakanti2, Meenakshi Bhat3
1Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, Room 840, 8th floor, Mother and Child Block, Ansari Nagar, New Delhi, 110029, India. neerja17@gmail.com.
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 mut0 (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.
Insights
Methylmalonic acidemia (MMA) presents a diverse clinical and molecular spectrum. MMA cblC subtype is most common, and outcomes depend on molecular defect, age, and presentation severity.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Methylmalonic acidemia (MMA) is a group of inherited metabolic disorders.
- These disorders result from defects in the metabolic pathway of methylmalonic acid, leading to its accumulation.
- Understanding the clinical and molecular variations is crucial for diagnosis and management.
Purpose of the Study:
- To investigate the clinical features, biochemical abnormalities, genetic variations, and outcomes in a cohort of patients with Methylmalonic acidemia.
- To identify the most common molecular subtypes of MMA and their associated clinical presentations.
- To explore the factors influencing patient outcomes in MMA.
Main Methods:
- Retrospective analysis of medical records from 30 patients diagnosed with MMA.
- Evaluation of patient phenotypes, biochemical data, and molecular genetic testing results.
- Assessment of treatment responses, particularly to Vitamin B12, and patient outcomes, including mortality.
Main Results:
- The study included 30 patients from 27 families, with consanguinity noted in 41%.
- Acute metabolic decompensation occurred in 57% of patients. MMA cblC was the most frequent molecular subtype (n=8), followed by MMA mutase defects.
- Mortality was 30%, with severe outcomes in isolated MMA mut0 and MMA cblB subtypes.
Conclusions:
- MMA exhibits a wide spectrum, with MMA cblC being the most prevalent subtype, followed by MMA mutase defects.
- Patient outcomes are significantly influenced by the specific molecular defect, age at diagnosis, and disease severity.
- Early detection and timely management are critical for improving outcomes in patients with Methylmalonic acidemia.
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