Pompe disease: literature review and case series

Abstract

Pompe disease is a rare multi-systemic metabolic myopathy caused by autosomal recessive mutations in the acidic alpha glucosidase (GAA) gene. Significant progress had been made in the diagnosis and management of patients with Pompe disease. Here, we describe our experience with 12 patients with various forms of Pompe disease including 4 potentially pathogenic, novel GAA variants. We also review the recent the recent advances in the pathogenesis, diagnosis, and treatment of individuals with Pompe disease.

Keywords: Autosomal recessive; Enzyme replacement therapy; Hypotonia; Lysosomal glycogen storage disease; Metabolic myopathy; Newborn screening.

Figure 1

Schematic representations of GAA genomic location and structure (A) and its protein structure (B). GAA maps to chr17q25.3 and consists of 20 (19 coding) exons which encode 952 amino acids. Mutations (DNA variants) identified in this study are shown according to their respective genomic position. Novel variants are boxed. GAA has 4 isoforms (a-d), 2 catalytically active sites (*), 3 disulfide bonds (s-s) and 7 N-linked glycosylation sites (∇).

Figure 2

Histological examination of muscle biopsies of patients 9 (A, B) and 4 (C, D). H&E stained muscle biopsy (A) from patient 9 shows extensive vacuolar changes (asterisk) and positive acid phosphatase aggregates (#) in panel B. The H&E stained muscle biopsy (C) from patient 4 is essentially unremarkable while the muscle electron micrograph (D) showed membrane bound glycogen deposits and mildly distorted mitochondrial morphology.

Figure 3

Photographs of patients with infantile onset Pompe disease. The sib pair (A, B; patients 1 and 2 respectively) have non-classical IOPD while patient 3 (C) has classical IOPD with macroglossia, tracheostomy and severe hypotonia. Abnormal EKG of patient 3 shows sinus tachycardia, short PR interval, ST segment and T wave abnormalities as well as left ventricular hypertrophy.