Myophosphorylase Deficiency

Clinical History

This 25-year-old patient presented with episodes of fatigue, myalgias and muscle weakness following even low-level exertion. These symptoms have been present since they were a child. During a recent episode elevated CPK (2000) were detected.  They indicate dark colored urine in association with one of these episodes in the past.

Muscle biopsy showed mild nonspecific variation in myofiber diameter on H&E and modified Gomori Trichrome stained sections. Enzyme histochemical staining for NADH-TR, esterase, myoadenylate deaminase, succinic acid dehydrogenase and cytochrome oxidase were unremarkable.

The provided image of myophosphorylase enzyme histochemical stain shows features most consistent with what disease?

Correct Answer:

This patient’s muscle biopsy shows complete absence of enzyme histochemical staining for myophosphorylase (muscle glycogen phosphorylase), while other enzyme histochemical stains show appropriate reactivity. This finding is most consistent with myophosphorylase deficiency (GSD 5 / McArdle disease).

This disorder is due to mutations involving the PYGM gene. It follows an autosomal recessive pattern of inheritance.

In most of the adult cases we have encountered the muscle biopsy has shown mild nonspecific changes, without obvious accumulation of glycogen (i.e. no glycogen lakes).

Reference(s) / additional reading:

Llavero F, et al. McArdle Disease: New Insights into Its Underlying Molecular Mechanisms. Int J Mol Sci. 2019 Nov 25;20(23):5919. doi: 10.3390/ijms20235919. PMID: 31775340; PMCID: PMC6929006.

Quinlivan R, et al. Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V). Cochrane Database Syst Rev. 2014 Nov 12;2014(11):CD003458. doi: 10.1002/14651858.CD003458.pub5. PMID: 25391139; PMCID: PMC7173724.

Quinlivan R, et al. McArdle disease: a clinical review. J Neurol Neurosurg Psychiatry. 2010 Nov;81(11):1182-8. doi: 10.1136/jnnp.2009.195040. Epub 2010 Sep 22. PMID: 20861058.