Malonic aciduria

Malonic aciduria (also known as malonyl-CoA decarboxylase deficiency or malonic acidemia) is an extremely rare autosomal recessive inborn error of metabolism caused by mutations in the MLYCD gene, which encodes the enzyme malonyl-CoA decarboxylase. This enzyme is responsible for converting malonyl-CoA to acetyl-CoA, and its deficiency leads to accumulation of malonic acid and methylmalonic acid in body fluids. The condition primarily affects the nervous system, heart, and metabolic pathways, with disruption of mitochondrial fatty acid oxidation playing a central role in its pathophysiology. Clinical features typically present in infancy or early childhood and include developmental delay, seizures, hypoglycemia, metabolic acidosis, cardiomyopathy (particularly dilated cardiomyopathy), and failure to thrive. Gastrointestinal symptoms such as vomiting and diarrhea may also occur. The severity of the disease is variable, with some patients experiencing life-threatening metabolic crises during periods of illness or fasting, while others may have a milder phenotype. Diagnosis is established through detection of elevated malonic acid in urine organic acid analysis, often accompanied by mildly elevated methylmalonic acid, and can be confirmed by molecular genetic testing of the MLYCD gene or enzyme activity assays. Treatment is primarily supportive and includes dietary management with avoidance of prolonged fasting, a low-fat diet, and carnitine supplementation to address secondary carnitine deficiency. During acute metabolic decompensation, intravenous glucose and supportive care are essential. Cardiac function should be monitored regularly due to the risk of cardiomyopathy. Early diagnosis and management can improve outcomes, though long-term prognosis varies depending on disease severity.

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