From the Guidelines
Methylmalonic acidemia (MMA) is diagnosed through newborn screening and confirmed with blood and urine tests showing elevated methylmalonic acid levels, along with genetic testing, and treatment involves a multi-faceted approach focusing on dietary management, medication, and supportive care. The diagnosis of MMA is crucial for initiating timely treatment and preventing long-term complications. According to 1, laboratory analysis of organic acids is a technical standard of the American College of Medical Genetics and Genomics (ACMG), and MMA is one of the disorders that can be identified through urine organic acid analysis.
Diagnosis
The diagnosis of MMA involves:
- Newborn screening
- Blood and urine tests to confirm elevated methylmalonic acid levels
- Genetic testing to identify the underlying genetic defect
- Urine organic acid analysis, which can detect elevated levels of methylmalonic acid and other metabolites associated with MMA, as described in 1 and 1
Treatment
The treatment of MMA involves:
- Dietary management: a low-protein diet (0.5-1.5 g/kg/day) with supplementation of special medical foods low in propiogenic amino acids
- Medication regimens: intramuscular hydroxocobalamin (1 mg daily initially, then 1-2 mg weekly) for vitamin B12-responsive forms, and oral biotin (5-10 mg daily) for some patients
- Carnitine supplementation: 50-100 mg/kg/day to help remove toxic metabolites
- Supportive care: regular monitoring of metabolic parameters, growth, and development, and emergency protocols for acute decompensation, including hospitalization for intravenous fluids and close monitoring, as described in 1
Long-term Management
Long-term management of MMA involves:
- Lifelong dietary restrictions and medication adherence
- Regular monitoring of metabolic parameters, growth, and development
- Emergency protocols for acute decompensation, including hospitalization for intravenous fluids and close monitoring
- Consideration of liver transplantation (LT) for patients with frequent episodes of metabolic decompensation, uncontrollable hyperammonemia, restricted growth, or severe impairment of health-related quality of life, as described in 1
The rationale behind this approach is to reduce the accumulation of toxic metabolites by limiting precursor amino acids, enhancing the removal of harmful compounds, and supporting overall metabolism. Early diagnosis and consistent management are critical to preventing neurological damage and other complications associated with MMA.
From the Research
Diagnosis of Methylmalonic Acidemia (MMA)
- MMA is a genetic condition affecting cobalamin metabolism, causing elevated serum and urine methylmalonic acid without B12 deficiency 2
- Diagnosis of MMA mainly depends on clinical symptoms, newborn screening, biochemical detection, gene sequencing, and neuroimaging diagnosis 3
- A comprehensive diagnostic approach involves investigations of metabolites with tandem mass spectrometry, organic acid analysis with gas chromatography, enzymatic studies with fibroblast cell culture, and finally, mutation analysis 4
- The diagnosis is essential for specific treatment and favorable evolution to prevent sequelae 5
Treatment Options for MMA
- Improvement is rapid with IV cobalamin and a specialized diet 2
- Treatment includes high-dose vitamin B12 and a specialized diet with low protein, including restricted isoleucine, threonine, methionine, and valines, as well as a high caloric content 2
- Early detection and diagnosis are crucial for the treatment and quality of life of patients with MMA 3
Clinical Presentation and Neuroimaging
- MMA presents with ketoacidotic hyperammonemic coma in newborns and can result in neonatal death or severe neurological disability 2
- The accumulation of methylmalonic acid and other metabolites in the body of patients causes brain tissue damage, which can manifest as various degrees of intellectual disability and severe neurological dysfunction 3
- Neuroimaging examination has important clinical significance in the diagnosis and prognosis of MMA 3