Glycogen Storage Disease Type V - McArdle Disease
This page addresses the possible ophthalmologic manifestations of glycogen storage disease type V, a rare metabolic disorder.
Glycogen storage disease type V
Glycogen storage disease type V (GSD5) , also known as McArdle's disease , is a metabolic disorder caused by a deficiency of myophosphorylase, the muscle enzyme of glycogen phosphorylase. Its incidence is reported as one in 100,000 .
Two autosomal recessive forms of this disease occur, childhood-onset and adult-onset. The gene for myophosphorylase, PYGM (the muscle-type of the glycogen phosphorylase gene), is located on chromosome 11q13. Myophosphorylase is involved in the breakdown of glycogen to glucose. The enzyme removes 1,4 glycosyl residues from outer branches of glycogen and adds inorganic phosphate to form glucose-1-phosphate. Cells form glucose-1-phosphate instead of glucose during glycogen breakdown because the polar, phosphorylated glucose cannot leave the cell membrane and so is marked for intracellular catabolism.
Clinically, it manifests as exercise intolerance and acute episodes of contractures, associated with rhabdomyolysis and myoglobinuria.
- A muscle biopsy will note the absence of myophosphorylase in muscle fibers. In some cases, acid-Schiff stained glycogen can be seen with microscopy.
- Genetic sequencing of the PYGM gene
Several case-reports and case-series have associated GSD5 with a retinal pattern dystrophy . Glucose is the major energy substrate for retinal metabolism and its source to the outer retina is the retinal pigmented epithelium (RPE) which manages the conversion of glycogen to glucose. It has been demonstrated that, in human RPE, the glycogen phosphorylase enzyme present is the muscle isoform (myophosphorylase).  This reinforces the pathogenesis of retinopathy in McArdle disease.
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