Longitudinal case study and phenotypic multimodal characterization of McArdle disease-linked retinopathy: insight into pathomechanisms

ABSTRACT

Background: We present a longitudinal clinical characterization of PYGM-linked pattern dystrophy in an adult male patient.

Materials and Methods: A patient affected by McArdle disease (glycogen storage disease type V) and homozygous for the nonsense variant PYGM c.148C>T p.(Arg50*) underwent ophthalmic examinations over a 9-year-interval, including fundus photography, fundus autofluorescence, optical coherence tomography (OCT), OCT-angiography and electroretinography (ERG).

Results: At age 52, the patient was asymptomatic but yellow flecks were first observed in the macula of both eyes. This yellow flecks at the posterior pole progressed towards a pattern-like dystrophy over a 5-year-period. By fundus autofluorescence imaging the appearance of new hyperautofluorescent flecks and the extension of existing ones was observed over time. Concomitantly, a slow progression of the size of atrophic areas was seen at the posterior pole. Scotopic ERGs were within normal limits, but photopic Flicker responses were decreased, indicating reduced cone function.

Conclusions: This additional case of PYGM-linked pattern dystrophy further confirms retinopathy as a clinical phenotype associated with McArdle disease. PYGM expression pattern suggests a disease mechanism involving impaired glycogen metabolism both in the retinal pigment epithelium and in cone photoreceptors.

KEYWORDS:

• Retinopathy
• glycogen storage disease
• glycogen phosphorylase
• PYGM
• pattern dystrophy

Acknowledgments

We would like to thank the patient for his continuous interest and kind cooperation.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.