Pompe disease is a progressive metabolic myopathy caused by deficiency in lysosomal acid a-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 GM 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 mis-diagnosed 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. (C) 2012 Elsevier Inc. All rights reserved.