The Diagnostic Path to Pompe Disease

Abstract

Pompe disease (PD) is a lysosomal disease that primarily affects skeletal and smooth muscles due to a deficiency of acid alpha glucosidase.The resulting clinical phenotype reflects a continuum ranging from severe infantile to later onset forms of PD. Early diagnosis is essential to prevent long-term complications and/or disease progression through initiation of enzyme-replacement therapy. The diagnostic path to PD starts with the ascertainment of medical and family history as well as an in-depth clinical and neurological evaluation. The involvement of proximal muscle groups including hip and thigh muscles as well as the diaphragm is characteristic for later onset PD.Once PD is considered creatine kinase (CK) should be measured, realising that levels may be within normal limits in end stage disease.Ultimately, diagnostic confirmation is readily achieved by enzyme analysis in dried blood spots and/or leukocytes followed by molecular analysis. Muscle biopsy is not sensitive enough for diagnostic testing of PD but may be an important diagnostic test for the differential diagnosis of myopathies. Future diagnostic approaches include whole exome and genome sequencing, which may contribute to our understanding of genotype-phenotype correlation and phenotype prediction. KeywordsPompe disease, alpha glucosidase, glycogen storage disease II, diagnosis, laboratory testing, dried blood spot Disclosure: Olaf A Bodamer is a member of Genzyme speaker's bureau and has also received research funding. Christina Y Hung has no conflicts of interest to declare.