Acid maltase deficiency (glycogen-storage disease type II or GSD II) is caused by defects in the lysosomal acid aglucosidase gene. Three clinical phenotypes of the disease are usually distinguished: infantile, juvenile and adult. Patients with the severe infantile form (Pompe's disease) have muscle weakness and cardiomyopathy leading to death before the age of two years, but significant improvement has been observed in few patients treated with recombinant human a—glucosidase (RhGAA).

 

Patients with juvenile or the adult form of GSDII present with a slowly progressive myopathy frequently associated with respiratory insufficiency due to diaphragmatic involvement. Age at onset, and severity of muscle weakness are greatly variable in these patients. Moreover there is no clear correlation between the slope of evolution of limb muscle weakness and respiratory involvement. Beginning of trials with recombinant RhGAA in adult-onset AMD is expected in late 2003 . In anticipation of these therapeutic trials we propose to collect exhaustive data on all patients affected by juvenile and late-onset AMD in France, and to study the natural history of the disease during 18 months on 20 patients regularly examined at the Institute of Myology.

 

Exhaustive clinical, biochemical and molecular data will be collected anonymously in a computer data base in collaboration with specialists of muscle disorders and the "INSERM-AFM" research network on Glycogenosis type II. A clinical questionnaire established by the department of Medical Genetics of Rotterdam will be also proposed to all patients, in close collaboration with the International Pompe association (IPA). The study of natural history will rely on a quantitative assessment of limb muscle weakness with QMT and Biodex, an evaluation of muscular glycogen content in thigh and calf by 13C spectroscopy NMR, and measurements of diaphragmatic function. Those parameters will be measured three times during a 18 months period at the Institute of Myology (limb muscles assessment) and in Raymond-Poincaré Hospital (pulmonary functions). The results of this study will allow: i) To evaluate the number of patients with adult-onset acid maltase deficiency in France, and the disease severity in all of them; 2) To appreciate the rate of evolution of the disease in a subgroup of patients with a strict protocol of clinical follow-up. Those data should also facilitate the identification of patients eligible for therapeutic trials in France, and to better appreciate the response to treatments.