Late-Onset Glycogen Storage Disease Type II (Pompe's Disease) with a Novel Mutation: A Malaysian Experience

Abstract

Pompe's disease (acid maltase deficiency, glycogen storage disease type II) is an autosomal recessive disorder caused by a deficiency of lysosomal acid α-1,4-glucosidase, resulting in excessive accumulation of glycogen in the lysosomes and cytoplasm of all tissues, most notably in skeletal muscles. We present a case of adult-onset Pompe's disease with progressive proximal muscles weakness over 5 years and respiratory failure on admission, requiring prolonged mechanical ventilation. Electromyography showed evidence of myopathic process with small amplitudes, polyphasic motor unit action potentials, and presence of pseudomyotonic discharges. Muscle biopsy showed glycogen-containing vacuoles in the muscle fibers consistent with glycogen storage disease. Genetic analysis revealed two compound heterozygous mutations at c.444C>G (p.Tyr148∗) in exon 2 and c.2238G>C (p.Trp746Cys) in exon 16, with the former being a novel mutation. This mutation has not been reported before, to our knowledge. The patient was treated with high protein diet during the admission and subsequently showed good clinical response to enzyme replacement therapy with survival now to the eighth year. Conclusion. In patients with late-onset adult Pompe's disease, careful evaluation and early identification of the disease and its treatment with high protein diet and enzyme replacement therapy improve muscle function and have beneficial impact on long term survival.

Figure 1

Hematoxylin and Eosin (H&E) staining shows vacuolar myopathy.

Figure 2

Vacuoles are stained with periodic acid Schiff (PAS).

Figure 3

DNA sequence electropherograms of the two heterozygous compounds detected in this patient. The c.444C>G (p.Tyr148*) mutation is identified in exon 2 and c.2238G>C (p.Trp746Cys) mutation is identified in exon 16 of the GAA gene.

Figure 4

Multiple sequence alignments of GAA homologous sequences in different species are shown. Nonsense mutation reported in this study is highlighted by a red rectangle, illustrating that the p.Tyr148* mutation is in a highly conserved region.