Mevalonic aciduria

Mevalonic aciduria (MVA), also known as mevalonate kinase deficiency (severe form) or mevalonicaciduria, is a rare autosomal recessive inborn error of cholesterol and isoprenoid biosynthesis caused by pathogenic variants in the MVK gene, which encodes the enzyme mevalonate kinase. It represents the most severe end of the mevalonate kinase deficiency spectrum, with hyper-IgD syndrome (HIDS) being the milder form. The deficiency of mevalonate kinase leads to accumulation of mevalonic acid in body fluids and impaired production of downstream isoprenoids essential for numerous cellular functions. Mevalonic aciduria affects multiple organ systems. Key clinical features include recurrent febrile crises (often triggered by infections or vaccinations), failure to thrive, developmental delay and intellectual disability, progressive cerebellar ataxia, dysmorphic facial features, hepatosplenomegaly, lymphadenopathy, and ocular abnormalities such as cataracts and uveitis. Patients may also develop anemia, diarrhea, and myopathy. The disease typically presents in infancy or early childhood, and severely affected individuals may have a shortened lifespan due to recurrent inflammatory episodes and progressive neurological deterioration. There is currently no curative treatment for mevalonic aciduria. Management is primarily supportive and symptomatic. Anti-inflammatory therapies, including corticosteroids and biologic agents such as anakinra (an IL-1 receptor antagonist) and canakinumab, have been used to manage inflammatory episodes with variable success. Hematopoietic stem cell transplantation (HSCT) has been attempted in severe cases with some reported benefit, though outcomes remain uncertain. Nutritional support, physical therapy, and management of specific complications (such as cataracts) are important components of multidisciplinary care. Diagnosis is confirmed by elevated urinary mevalonic acid levels, reduced mevalonate kinase enzyme activity, and molecular genetic testing of the MVK gene.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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