Symptoms tend to resolve spontaneously around puberty. Myopathy often appears in adult life, long after liver symptoms have subsided. Adult-onset myopathies have been distinguished into two groups, distal and generalized (31). Patients with distal myopathy develop atrophy of leg and intrinsic hand muscles, often suggesting the diagnosis of motor neuron disease or peripheral Inhibitors,research,lifescience,medical neuropathy (32). The course is slowly progressive and

the myopathy is rarely crippling. Patients with generalized myopathy are more severely affected and often suffer from respiratory distress (31, 33). Although debrancher works in parallel with myophosphorylase, the symptoms of debrancher deficiency are very Inhibitors,research,lifescience,medical different from those of McArdle disease and cramps and myoglobinuria are exceedingly

rare. One reason for this discrepancy may be that in McArdle disease glycogen cannot be broken down at all, whereas in GSD III, the most peripheral portions of normal glycogen can be utilized, as shown by lactate production in vitro (Fig. ​(Fig.4).4). However, for this minor “spare fuel” to work in vivo, one has to postulate a constant recycling of the peripheral chains between glycogen and PLD, while most of the stored glycogen in GSD Inhibitors,research,lifescience,medical III appears to be in the form of PLD. Figure 4 Comparative lactate production through anaerobic glycolysis in vitro by muscle homogenates from normal controls, 3 patients with debrancher deficiency (P1, P2, P3) and one patient with McArdle disease. A more important explanation for the fixed, and mostly distal, weakness is the simultaneous involvement of muscle and nerve, as clearly documented both electrophysiologically and by nerve Inhibitors,research,lifescience,medical biopsy (34, 35). Although the glycogenoses have been studied for almost one century (29), this Symposium documents how new enzyme defects are still

being discovered, clinical variants of known defects are being described, pathogenetic mechanisms are incompletely understood, molecular studies have not provided clear genotype/phenotype Tideglusib molecular weight relationships, and therapy is still woefully inadequate. Clearly, much remains to be done. Acknowledgements Inhibitors,research,lifescience,medical Part of this work has been supported by a grant from the Muscular Dystrophy Thiamine-diphosphate kinase Association.
Glycogen storage disease type II (GSD-II), also known as Pompe disease, or acid maltase deficiency (AMD), is an autosomal recessive genetic disorder that encompasses a range of clinical phenotypes, but myopathy is common to all. This “variable expressivity” manifests primarily as variances in age of onset of disease symptoms, as well which organs are pathologically involved. The most severe form of GSD-II is the infantile-onset form, and was originally described by Dr. Pompe. These severely affected infants may appear normal at birth, but soon develop generalized muscle weakness and cardiac myopathy manifesting initially as a hypertrophic cardiomyopathy.