Glycogen Storage Disease Type V - McArdle Disease

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Article initiated by:

João Heitor Marques, João Melo Beirão

All contributors:

Leo A. Kim, MD, PhD, Sun Young (Sunny) Lee, MD, PhD, João Heitor Marques, Jennifer I Lim MD, Yicheng Bao, M D

Assigned editor:

Sun Young (Sunny) Lee, MD, PhD

Review:

Assigned status Up to Date

 by Sun Young (Sunny) Lee, MD, PhD on May 28, 2024.

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Contributing Editors:	add

This page addresses the possible ophthalmologic manifestations of glycogen storage disease type V, a rare metabolic disorder.

Disease Entity

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 .

Etiology

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.

Clinical manifestations

Clinically, it manifests as exercise intolerance and acute episodes of contractures, associated with rhabdomyolysis and myoglobinuria.

Diagnosis

• 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

Retinal appearance on color imaging (left panels) and fundus autofluorescence (FAF) imaging (right panels). A, Color fundus images from patient 1. B, Short-wavelength (488-nm) posterior pole (55°) FAF images from patient 1. C, D, Corresponding images from patient 2. E, F, Corresponding images from patient 3. G, H, Pseudocolor image and 488-nm FAF image from patient 4. In all cases, yellow reticular lesions are visible on color imaging, with atrophy in patient 1 and small areas of pigmentary change in patients 2, 3, and 4. Fundus autofluorescence (FAF) shows reticular hyperautofluorescence (likely to result from loss of photoreceptor outer segments, accumulation of fluorophore in the retinal pigment epithelium [RPE], or both) in all cases, with additional dark areas indicating RPE atrophy in patient 1.

Ophthalmologic manifestations

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.