The variability of Pompeʹs disease : a clinical, biochemical and genetic study of glycogen storage disease type 2, or acid maltase deficiency

textabstractPompe's disease is an autosomal recessive metabolic disorder, characterized by storage of glycogen in organs and tissues, and associated with deficiency of the lysosomal enzyme acid maltase (acid a -I, 4-glucosidase, E. C. 3 .2.1.20). Synonyms for Pompe's disease are "glycogen storage disease type 2" and "acid maltase deficiency". Several clinical variants have become known. In this thesis a generalized form and a muscular form are distinguished. The generalized form is a progressive disease of infancy. It is characterized by a failure to thrive, cardiorespiratory difficulties and weakness with hypotonia, and leads to death within the first two years of life. The muscular form may occur in childhood or even in adults. It causes a slowly progressive myopathy which is ultimately fatal, usually because of respiratory insufficiency. Despite the wide variability in clinical manifestations, one and the same enzyme, lysosomal acid maltase, is deficient in both forms. The present study was prompted by two circumstances. The first was an exceptional combination of both clinical forms in one family: an infant suffered from the generalized form and her grandfather form the muscular form. The second reason was that data of 20 patients with this rare disorder (seven with the generalized form, and 13 with the muscular form) were available for study. This series consisted of patients known to the pediatrician Fernandes and the biochemist Koster in Rotterdam, both of whom have a special interest in the field of the glycogenoses, and of patients diagnosed by the neurologists Bethlem (Amsterdam), Busch (Rotterdam) and J ennekens Utrecht