Abstract
McArdle disease is caused by recessive mutations in PYGM gene. The condition is considered to cause a "pure" muscle phenotype with symptoms including exercise intolerance, inability to perform isometric activities, contracture, and acute rhabdomyolysis leading to acute renal failure. This is a retrospective observational study aiming to describe phenotypic and genotypic features of a large cohort of patients with McArdle disease between 2011 and 2019. Data relating to genotype and phenotype, including frequency of rhabdomyolysis, fixed muscle weakness, gout and comorbidities, inclusive of retinal disease (pattern retinal dystrophy) and thyroid disease, were collected. Data from 197 patients are presented. Seven previously unpublished PYGM mutations are described. Exercise intolerance (100%) and episodic rhabdomyolysis (75.6%) were the most common symptoms. Fixed muscle weakness was present in 82 (41.6%) subjects. Unexpectedly, ptosis was observed in 28 patients (14.2%). Hyperuricaemia was a common finding present in 88 subjects (44.7%), complicated by gout in 25% of cases. Thyroid dysfunction was described in 30 subjects (15.2%), and in 3 cases, papillary thyroid cancer was observed. Pattern retinal dystrophy was detected in 15 out of the 41 subjects that underwent an ophthalmic assessment (36.6%). In addition to fixed muscle weakness, ptosis was a relatively common finding. Surprisingly, dysfunction of thyroid and retinal abnormalities were relatively frequent comorbidities. Further studies are needed to better clarify this association, although our finding may have important implication for patient management.
Highlights
McArdle disease, known as glycogen storage disease type V, is a genetic condition caused by recessive mutations in the PYGM gene on chromosome 11, encoding the muscle isoform of glycogen phosphorylase
The first description dates back to 1951 by the Scottish physician Brian McArdle,[1] who suspected a deficiency in glycogen metabolism in a patient who could not produce lactate during ischaemic exercise; the underlying defect in muscle phosphorylase was later described by Mommaerts et al.[2] in 1959 and the genetic cause was not discovered until several years later.[3]
McArdle disease is clinically characterized by childhood or early adult onset of exercise intolerance, muscle fatigue, myalgia, contractures and episodes of rhabdomyolysis induced by brief intense isometric and anaerobic exercise.[7]
Summary
McArdle disease, known as glycogen storage disease type V, is a genetic condition caused by recessive mutations in the PYGM gene on chromosome 11, encoding the muscle isoform of glycogen phosphorylase ( known as myophosphorylase). The first description dates back to 1951 by the Scottish physician Brian McArdle,[1] who suspected a deficiency in glycogen metabolism in a patient who could not produce lactate during ischaemic exercise; the underlying defect in muscle phosphorylase was later described by Mommaerts et al.[2] in 1959 and the genetic cause was not discovered until several years later.[3] Despite being considered a rare disorder, with an estimated prevalence between 1:100 000 and 167 000,4,5 McArdle disease is the most common muscle glycogenosis.[6] Deficiency of myophosphorylase prevents the metabolism of glycogen in skeletal muscle cells leading to an inability to generate energy from glycogenolysis.[7]. Molecular genetic testing (sequencing of PYGM in circulating leukocytes),[9] has replaced direct assay of myophosphorylase activity, obtained via a muscle biopsy,[10] as the most helpful initial diagnostic test
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
