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DOI: 10.1055/a-2656-0505
Muscle Biopsy as a Decisive Tool in a Pediatric Case with Overlapping Genetic Findings for McArdle Disease and Dystrophinopathy
Muskelbiopsie als entscheidendes Instrument in einem pädiatrischen Fall mit überlappenden genetischen Befunden für Morbus McArdle und Dystrophinopathie
Introduction
McArdle disease, also known as glycogen storage disease type V (GSD V, OMIM 232600), is an inherited metabolic disorder characterized by a deficiency of muscle glycogen phosphorylase (myophosphorylase, E.C. 2.4.1.1). It is inherited in an autosomal recessive manner and leads to the accumulation of glycogen in tissues, primarily skeletal muscles. Clinical manifestations are typically systemic, but in some cases, the defect may be limited to specific tissues (Joshi PR et al., Biomedicines 2020; 8: 33).
McArdle disease is the most common muscle glycogenosis and is characterized by exercise intolerance with myalgia and stiffness of exercising muscles, which are relieved by rest. Disease onset generally occurs during childhood; however, diagnosis is often delayed until adulthood. It was first described in 1951 (McArdle B. Clin Sci 1951; 10: 13–35) and the gene encoding myophosphorylase (PYGM, 608455), located on chromosome 11q13.1, was first identified in 1984 (Lebo et al., Science 1984; 225: 57–59). Diagnosis is established in individuals with suggestive clinical findings through the identification of biallelic PYGM pathogenic variants via molecular genetic testing. In cases where genetic testing is inconclusive, the diagnosis can be confirmed by assessing muscle myophosphorylase enzyme activity in a muscle biopsy specimen.
Dystrophinopathies are a group of X-linked muscle disorders, including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and the recently identified DMD-associated dilated cardiomyopathy (DCM). The most accurate diagnostic approach involves DMD gene, located on chromosome Xp21.2-p21.1, deletion-duplication analysis, which identifies pathogenic variants in 60% to 70% of cases, while sequencing is required for the remaining patients (Morales A et al., 2023; In: StatPearls [Internet] 2024).
This case report aims to describe a four-year-old male patient with a two-year history of exertional leg pain (myalgia) and muscle fatigue, particularly during activities such as stair climbing and prolonged walking. Given the clinical presentation and markedly elevated creatine kinase (CK) levels, McArdle disease and dystrophinopathies were considered among the initial differential diagnoses. The report highlights the diagnostic challenges in differentiating McArdle disease from dystrophinopathies in a pediatric patient and underscores the importance of genetic analysis and muscle biopsy in establishing the diagnosis.
Publication History
Article published online:
11 August 2025
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