Diagnosis by Electron Microscopy of Late Onset Pompe Disease with Previous Normal or Non Specific Muscle Biopsies by Light Microscopy

Abstract

ntroduction: The diagnosis of late onset Pompe disease may be delayed for many years following onset of muscle eakness. Muscle biopsy may be normal or non specific by light microscopy. ase Reports: Two men are described with late onset acid maltase deficiency and delay from clinical onset to iagnosis of 38 and 30 years, respectively, based on reduced alpha-glucosidase activity on a dried blood spot. The rst man experienced the onset of proximal lower limb muscle weakness at age 27 years. He underwent muscle iopsy at age 43 years which was reported as showing fibre type variability but no diagnostic abnormality. He was iagnosed at age 65 years following a review of his biopsy by electron microscopy which demonstrated multiple mall membrane bound vacuoles containing glycogen particles. The second patient experienced lower limb weakess at 40 years of age and underwent biopsies at 52 and 61 years of age, the first reported as normal and the second s non specific with increased fibre size variability. He was finally diagnosed by electron microscopy at age 70. Both atients developed dyspnea and orthopnea early in the clinical course requiring nocturnal ventilatory support. onclusion: These patients emphasize the importance of considering the diagnosis of late onset Pompe disease even n patients with normal or non specific changes on muscle biopsy. The clinical features strongly suggesting this isorder are respiratory involvement with orthopnea early in the course of disease, and predominantly lower limb roximal weakness. Electron microscopy may be diagnostic when histochemistry has not shown the characteristic ndings of acid phosphatase staining and increased glycogen. Diagnosis based on dried blood spot should be onsidered when there is a clinical suspicion of PD and is simple and inexpensive.