MMAB

Methylmalonic aciduria type B (MMAB) is a rare genetic disorder characterized by a deficiency of the enzyme cobalamin (vitamin B12) synthesis. This condition is part of a broader group of disorders known as methylmalonic acidemia, which leads to the accumulation of methylmalonic acid in the blood and urine. MMAB specifically results from mutations in the MMAB gene, which plays a crucial role in the metabolic pathway that converts certain lipids and proteins into energy. This article provides an overview of MMAB, including its genetics, pathophysiology, clinical presentation, diagnosis, and treatment options.

Genetics

MMAB is caused by mutations in the MMAB gene located on chromosome 12. This gene is responsible for encoding a protein that is essential for the conversion of vitamin B12 into a coenzyme form. The mutations lead to a functional deficiency of this enzyme, disrupting the normal metabolism of certain fatty acids and amino acids. MMAB is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder.

Pathophysiology

The MMAB gene mutation leads to a deficiency in the synthesis of adenosylcobalamin, a coenzyme form of vitamin B12. This deficiency disrupts the normal function of methylmalonyl-CoA mutase, an enzyme critical for the conversion of methylmalonyl-CoA to succinyl-CoA. As a result, methylmalonic acid accumulates in the body's tissues and fluids, leading to the clinical manifestations of the disorder.

Clinical Presentation

The symptoms of MMAB can vary widely among affected individuals but typically include developmental delay, intellectual disability, failure to thrive, vomiting, dehydration, hypotonia (reduced muscle tone), and hepatomegaly (enlarged liver). Metabolic crises, characterized by ketoacidosis, hyperammonemia, or hypoglycemia, can occur in response to stress or infections. Without prompt treatment, these crises can be life-threatening.

Diagnosis

The diagnosis of MMAB is based on clinical presentation, laboratory findings of elevated methylmalonic acid in the blood and urine, and genetic testing confirming mutations in the MMAB gene. Early diagnosis and treatment are crucial for preventing complications and improving outcomes.

Treatment

There is no cure for MMAB, but treatment focuses on managing symptoms and preventing metabolic crises. Management strategies may include a low-protein diet to reduce the intake of amino acids that contribute to methylmalonic acid production, supplementation with vitamin B12 (which may be effective in some cases), and prompt treatment of infections or other stressors that can precipitate a metabolic crisis. In severe cases, organ transplantation, such as kidney or liver transplant, may be considered.

Prognosis

The prognosis for individuals with MMAB varies depending on the severity of the disorder, the age at diagnosis, and the effectiveness of the management plan. Early diagnosis and intervention can significantly improve the quality of life and lifespan of affected individuals.