A novel m.12908T>A mutation in the mitochondrial ND5 gene in patient with infantile-onset Pompe disease

Pompe disease is a progressive metabolic myopathy caused by deficiency in lysosomal acid α-glucosidase and results in cellular lysosomal and cytoplasmic glycogen accumulation. A wide spectrum of clinical phenotypes exists from hypotonia and severe cardiac hypertrophy in the first few months of life to a milder form with the onset of symptoms in adulthood. The disease is typically due to severe mutations in GAA gene. In the present study, we described a newborn boy with clinical features of Pompe disease particularly with hypertrophic cardiomyopathy, hypotonia and hepatomegaly. This case was at first misdiagnosed as mitochondrial disorder. Accordingly, we performed a mitochondrial mutational analysis that revealed a novel mutation m.12908T>A in the ND5 gene. Secondary structure analysis of the ND5 protein further supported the deleterious role of the m.12908T>A mutation, as it was found to involve an extended imbalance in its hydrophobicity and affect its function.

► A newborn boy with clinical features of Pompe disease was studied.
► A whole mitochondrial mutational analysis was performed.
► A novel mutation m.12908T>A in the MT-ND5 gene was detected.
► A deleterious role of the m.12908T>A mutation was supported.