The natural course of non-classic Pompe's disease; a review of 225 published cases

Abstract

Pompe's disease is a neuromuscular disorder caused by deficiency of lysosomal acid alpha-glucosidase. Recombinant human alpha- glucosidase is under evaluation as therapeutic drug. In light of this development we studied the natural course of cases not fitting the definition of classic infantile Pompe's disease. Our review of 109 reports including 225 cases shows a continuous spectrum of phenotypes. The onset of symptoms ranged from 0 to 71 years. Based on the available literature, no criteria to delineate clinical sub-types could be established.A common denominator of these cases is that first symptoms were related to or caused by muscle weakness. In general, patients with a later onset of symptoms seemed to have a better prognosis. Respiratory failure was the most frequent cause of death. CK, LDH, ASAT, ALAT and muscle glycogen levels were frequently but not always elevated. In most cases a muscle biopsy revealed lysosomal pathology, but normal muscle morphology does not exclude Pompe's disease. In 10% of the cases in which the enzyme assay on leukocytes was used, a normal alpha-glucosidase activity was reported. Data on skeletal muscle strength and function, pulmonary function, disability, handicap and quality of life were insufficiently reported in the literature. Studies of non-classic Pompe's disease should focus on these aspects, before enzyme replacement therapy becomes generally available.