Metabolic myopathies

Clinical presentation can be broadly divided into static or slowly progressive and dynamic phenotypes. Static or slowly progressive forms are mainly characterised by proximal limb-girdle weakness, with respiratory and cardiac involvement in some conditions, such as Pompe disease (glycogen storage disease type II) and glycogen storage diseases type III and IV. Dynamic forms typically present with episodic exercise-induced myalgia, exercise intolerance and rhabdomyolysis, often associated with myoglobinuria and hyperCKaemia. Mitochondrial myopathies may additionally present with progressive external ophthalmoplegia, ptosis, fatigue and multisystem involvement. Age of onset is highly variable, ranging from neonatal or infantile presentation, as seen in classic infantile and severe fatty acid oxidation defects, to childhood, adolescence or adulthood in disorders such as McArdle disease, late-onset Pompe disease, TK2 deficiency and carnitine palmitoyltransferase II deficiency. Specific peri-operative anaesthetic considerations have been established for several metabolic myopathies.

Due to insufficient data, no reliable statement on prevalence can currently be made.

A multitude of genes are currently associated with metabolic myopathies. The genetic forms span glycogen storage disorders, fatty acid oxidation defects and mitochondrial myopathies; examples include Pompe disease (GAA; lysosomal acid α-glucosidase deficiency), carnitine palmitoyltransferase II deficiency (CPT2; impaired long-chain fatty-acid oxidation) and TK2-related mtDNA depletion (TK2; progressive proximal and respiratory myopathy). Pompe and McArdle disease are encountered most frequently.

Metabolic myopathies follow different inheritance patterns, including autosomal rescessive, autosomal dominant, and X-linked forms.

• Where a metabolic myopathy is suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

• Mouraux C, Dangouloff T, Poleur M, Mackels L, Vanden Brande L, Daron A, et al. Epidemiological report and diagnostic approach used in the neuromuscular population of Liege, Belgium. Orphanet J Rare Dis. 2025;20(1):464. PMID: .
• Urtizberea JA, Severa G, Malfatti E. Metabolic myopathies in the era of next-generation sequencing. Genes (Basel). 2023;14(5):954. PMID: .
• van den Bersselaar LR, Heytens L, Silva HCA, Reimann J, Tasca G, Díaz-Cambronero Ó, et al. European Neuromuscular Centre consensus statement on anaesthesia in patients with neuromuscular disorders. Eur J Neurol. 2022;29(12):3486-3507. PMID: .