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  • Updated 11.05.2020
  • Released 02.25.2013
  • Expires For CME 11.05.2023

Nonlysosomal muscle glycogenoses

Introduction

Overview

Glycogen storage disorders or glycogenoses are a heterogenous group of inborn errors affecting carbohydrate metabolism. In this review of the muscle glycogenoses (excepting acid maltase deficiency and Danon disease, the only lysosomal glycogen storage diseases), the authors provide brief descriptions of the still increasing list of specific enzyme defects as well as a more general rational diagnostic framework. As a clinical approach, they divide the glycogenoses into 2 distinct groups: (1) those that cause exercise intolerance, cramps, and recurrent episodes of muscle breakdown (rhabdomyolysis) with myoglobinuria and (2) those clinically characterized by fixed progressive weakness. Finally, they present symptomatic therapeutic strategies found to be helpful in these conditions.

Key points

• Disorders of glycogen metabolism can be due to defects in glycogen synthesis or glycogen breakdown.

• These defects may result in deposits of normal glycogen, abnormal glycogen (phosphorylase-limit-dextrin, PLD), or polyglucosan. They may also result in the absence of glycogen (glycogenoses type 0).

• The most frequent muscle glycogenoses are McArdle disease (GSDV), Pompe disease (GSDII, not reviewed here), and debranching enzyme deficiency (GSDIII).

• GSD III and GSD IV (branching enzyme deficiency) cause congenital or later-onset weakness, sometimes accompanied by liver disease or cardiomyopathy. A late-onset form of GSD IV causes adult polyglucosan body disease (APBD), a motor neuron disease that can mimic amyotrophic lateral sclerosis. Lafora disease, better known as a progressive myoclonus epilepsy, is also a polyglucosan storage disease.

• PFK deficiency and McArdle disease can be differentiated by simple laboratory tests, such as increased bilirubin concentration and reticulocyte count without anemia (reflecting compensated hemolytic anemia) in PFK deficiency.

• The differential diagnosis of glycogenoses with exercise intolerance, cramps, and myoglobinuria includes other metabolic myopathies, especially defects of fatty acid oxidation and defects of the mitochondrial respiratory chain, and, more generally, all genetic causes of recurrent myoglobinuria.

• The differential diagnosis of glycogenoses with fixed weakness includes the muscular dystrophies, congenital myopathies, and other metabolic myopathies.

• Depending on the tissue specificity of the isozyme or enzyme subunit involved, glycogenoses can be confined to muscle or involve other tissues, such as erythrocytes, cardiac muscle, or the central nervous system.

• All muscle glycogenoses are inherited as autosomal recessive traits, excepting 2 variants of phosphorylase b kinase (PHK) deficiency and phosphoglycerate kinase (PGK) deficiency, which are X-linked disorders.

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