Myopathy and ataxia related to impaired mitochondrial function in mevalonate kinase deficiency

Background: Mevalonate kinase deficiency (MKD) is a rare genetic disorder, resulting in the lack of the mevalonate kinase enzyme (MVK), which is involved in the biosynthesis of cholesterol, non-sterol isoprenoids, and coenzyme Q10 (CoQ10). The more severe phenotype of MKD is known as mevalonic aciduria (MA), typically presenting as a multisystemic inflammatory syndrome with possible neurological manifestations, such as developmental delay, cerebellar ataxia, and retinopathy. Myopathy or isolated hyperCKemia have been rarely reported in association with MA. However, a few studies evidenced mitochondrial dysfunction in MVK deficient cells. Aim: To point out the connection between MKD, myopathy, and mitochondrial dysfunction, describing two cases of MA. Methods: We report on two unrelated patients with myopathy and ataxia, providing clinical, histological, biochemical, and genetic data of MKD. Results: Both patients were referred to the Neurology Department in the first year of life, due to muscle weakness, gait disturbances, and increased levels of CK value. Muscle biopsy was performed, showing some mitochondrial alterations and mild lipid storage. Interestingly, biochemical studies on muscle homogenate revealed a reduction of mitochondrial respiratory chain activities and CoQ10 levels. Genetic analysis confirmed the MKD diagnosis, evidencing a homozygous MVK gene mutation in the first case, and compound heterozygous mutations in the second one. Conclusion: This report describes two MKD cases with clinical and morphological evidence of muscle involvement in the spectrum of MA related to mitochondrial dysfunction.