Case of the Month
Edited by Robert N. Johnson, MD
Case #113, Nov, 2018
Joseph Alsberge, MD
A 29-year-old woman with pigmented yellow spots in both eyes.
Figure 1: Color photo montage of the right eye. Note the pigmented yellow spots in the macula (see inset) as well as scattered areas of similar appearing spots in the periphery, particularly in the nasal periphery.
Figure 2: Color photo montage of the left eye. Note similar pigmented yellow spots in the macula (see inset) as seen in the right eye. Also, there is a similar distribution of scattered areas of similar appearing spots in the periphery.
A 29-year-old woman presented for evaluation of yellow spots in both eyes.
On examination, visual acuity was 20/16 in the right eye and 20/20 in the left eye. The anterior segment examination was unremarkable. Dilated examination revealed pigmented yellow spots involving the macula and nasal mid-periphery of both eyes (Figures 1 and 2). Fundus autofluorescence showed focal areas of subtle hypoautofluorescence centrally with surrounding haloes of hyperautoflourescence (Figures 3 and 4). Optical coherence tomography revealed changes at the level of the retinal pigment epithelium (RPE) in both eyes (Figures 5 and 6).
Figure 3: Wide-field autofluorescence of the right eye. Note the subtle areas of central hypoautofluorescence with surrounding halo of hyperautofluorescence.
Figure 4: Wide-field autofluorescence of the left eye. Note the subtle areas of central hypoautofluorescence with surrounding halo of hyperautofluorescence.
Figure 5: SD-OCT horizontal (top) and vertical (bottom) scan of the right macula. Faint changes are noted at the level of the RPE
Figure 6: SD-OCT horizontal (top) and vertical (bottom) with detail of deposits above and below fovea (see Figure 2-detail for correlation) of the left eye. Note the RPE elevation and presence of surrounding subretinal hyperreflectivel material.
What is your Diagnosis?
Isolated pattern dystrophy (PRPH2/RDS), pattern dystrophy associated with systemic disease (e.g., pseudoxanthoma elasticum, myotonic dystrophy, maternally inherited diabetes and deafness, hereditary spastic paraplegia, McArdle disease), Stargart’s disease, central serous chorioretinopathy.
Additional History and Diagnosis
The patient reported a several year history of exercise intolerance due to fatigue and muscle cramping. A muscle biopsy had been performed and revealed a deficiency of glycogen phosphorylase, consistent with McArdle disease, a glycogen storage disease. She had no family history of retinal dystrophy. Given the medical history and clinical findings, the diagnosis of pattern dystrophy associated with McArdle disease was made.
McArdle disease (glycogen storage disease type V) is a rare genetic condition that is characterized by a deficiency of skeletal muscle glycogen phosphorylase, an enzyme that is responsible for breaking down muscle glycogen.1 This deficiency results in inability to mobilize muscle glycogen during exercise when anaerobic metabolism is required. Pattern dystrophy-type retinal findings have been reported in multiple patients with McArdle disease.2-5
McArdle disease is autosomal recessive and is associated with mutations in the PYGM gene on chromosome 11, which encodes skeletal muscle glycogen phosphorylase.1 Symptoms of the disease include fatigue and muscle cramping induced by exercise and relieved with rest. Intense exercise may lead to rhabdomyolysis. Laboratory studies may show elevated serum creatine kinase and myoblobinuria. Diagnosis of the disease requires a high index of suspicion and is based on a forearm exercise test showing inability to produce lactate, the absence of muscle glycogen phosphorylase on muscle biopsy, or DNA analysis of the PYGM gene.
Pattern dystrophy refers to a group of diseases that is characterized by patterned deposits of yellow, orange, or gray pigment in the macula and mid periphery. Isolated pattern dystrophies are most frequently associated with mutations in PRPH2 located on chromosome 6, and inherited in an autosomal dominant fashion.6 These dystrophies have been categorized into 5 principle groups based on their characteristic distribution of findings: adult-onset foveomacular vitelliform dystrophy, butterfly-shaped pigment dystrophy, reticular dystrophy of the RPE, multifocal pattern dystrophy simulating fundus flavimaculatus, and fundus pulverulentus.6 Retinal changes typical of isolated pattern dystrophy have also been associated with a number of systemic diseases including pseudoxanthoma elasticum,7 myotonic dystrophy, maternally inherited diabetes and deafness, and hereditary spastic paraplegia.6
The first case of pattern dystrophy in a patient with McArdle disease was reported in 1998 by Leonardy et al.,2 and several others have followed since.3-5 These cases describe bilateral, pigmented, yellow, reticular lesions at the level of the RPE involving the macula and periphery, very similar in appearance to the case we have shown here. Importantly, in recent series by Mahroo et al., patients with confirmed McArdle disease and pattern dystrophy lacked PRPH2 mutations.5 This suggests that though PRPH2-associated isolated pattern dystrophy and McArdle-associated pattern dystrophy share similar phenotypes, they are distinct entities.
The potential causative mechanism of pattern dystrophy in McArdle disease is unknown. As mentioned previously, McArdle disease results from a mutation in the PYGM gene on chromosome 11, leading to deficiency of skeletal muscle glycogen phosphorylase. Intriguingly, muscle glycogen phosphorylase isoforms have been detected in human RPE,8 so perhaps the McArdle’s-associated PYGM gene mutation has the potential to lead to RPE dysfunction. Alternatively, it is possible that the PYGM mutation could lead to dysregulation of another nearby genetic locus on chromosome 11 involved in RPE function.2,3
Take Home Points
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This Case of the Month was adapted from the article “Retinal Dystrophy in a Patient with McArdle Disease” by Joseph Alsberge, Judy Chen, Ali Zaidi, and Arthur Fu, published online in Retinal Cases & Brief Reports on August 1, 2018.4
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