The glycogen storage diseases and related disorders

Abstract

The liver glycogen storage disorders (GSDs) comprise GSD I, the hepatic presentations of GSD III, GSD IV, GSD VI, the liver forms of GSD IX, and GSD 0. GSD I, III, VI, and IX present similarly with hypoglycemia, marked hepatomegaly, and growth retardation. GSD I is the most severe affecting both glycogen breakdown and gluconeogenesis. In GSD Ib there is additionally a disorder of neutrophil function. Most patients with GSD III have a syndrome that includes hepatopathy, myopathy, and often cardiomyo pathy. GSD VI and GSD IX are the least severe: there is only a mild tendency to fasting hypoglycemia, liver size normalises with age, and patients reach normal adult height. GSD IV manifests in most patients in infancy or childhood as hepatic failure with cirrhosis leading to end-stage liver disease. GSD 0 presents in infancy or early childhood with fasting hypoglycemia and ketosis and, in contrast, with postprandial hyperglycemia and hyperlactatemia. Treatment is primarily dietary and aims to prevent hypoglycemia and suppress secondary metabolic decompensation. This usually requires frequent feeds by day, and in GSD I and in some patients with GSD III, continuous nocturnal gastric feeding. The muscle glycogenoses fall into two clinical groups. The first comprises GSD V, GSD VII, the muscle forms of GSD IX (VIII according to McKusick), phosphoglycerate kinase deficiency (IX according to McKusick), GSD X, GSD XI, GSD XII and GSD XIII, and is characterised by exercise intolerance with exercise-induced myalgia and cramps, which are often followed by rhabdomyolysis and myoglobinuria; all symptoms are reversible with rest. Disorders in the second group, consisting of the myopathic form of GSD III, and rare neuromuscular forms of GSD IV, manifest as sub-acute or chronic myopathies, with weakness of trunk, limb, and respiratory muscles. Involvement of other organs (erythrocytes, central or peripheral nervous system, heart, liver) is possible, as most of these enzymes defects are not confined to skeletal muscle. Generalized glycogenoses comprise GSD II, caused by the deficiency of a lysosomal enzyme, and Danon disease due to the deficiency of a lysosomal membrane protein. Recent work on myoclonus epilepsy with Lafora bodies (Lafora disease) suggests that this is a glycogenosis, probably due to abnormal glycogen synthesis. GSD II can be treated by enzyme replacement therapy, but there is no specific treatment for Danon and Lafora disease. © 2006 Springer Medizin Verlag Heidelberg.