Metabolic myopathies: a practical approach

Abstract

Metabolic myopathies are a diverse group of rare genetic disorders and their associated muscle symptoms may be subtle. Patients may present with indolent myopathic features, exercise intolerance or recurrent rhabdomyolysis. Diagnostic delays are common and clinicians need a high index of suspicion to recognise and differentiate metabolic myopathies from other conditions that present in a similar fashion. Standard laboratory tests may be normal or non-specific, particularly between symptomatic episodes. Targeted enzyme activity measurement and next-generation genetic sequencing are increasingly used. There are now specific enzyme replacement therapies available, and other metabolic strategies and gene therapies are undergoing clinical trials. Here, we discuss our approach to the adult patient with suspected metabolic myopathy. We outline key features in the history and examination and discuss some mimics of metabolic myopathies. We highlight some disorders of glycogen and fatty acid utilisation that present in adulthood and outline current recommendations on management.

Beneficial Effects of Ketogenic Diet on Phosphofructokinase Deficiency (Glycogen Storage Disease Type VII)

“…The importance of free fatty acids for muscle oxidative metabolism has also been revealed in Tarui disease, and patients with this disease have been shown to benefit from substrates available after overnight fasting or triglyceride infusion during aerobic exercise (4). Indeed, glucose would not have a favorable effect on their cardiorespiratory capacity, and glucose ingestion could even worsen the condition (4,5). Patients with Tarui disease, unlike in McArdle's disease, do not show the second-wind phenomenon, an exercise-related increase in the capacity for muscle oxidative phosphorylation (6,7).…”

Pearls & Oy-sters: A curable myopathy manifesting as exercise intolerance and respiratory failure

“…If this triage for lipid accumulation is normal, a muscle biopsy that may reveal that lipid storage in MADD should be considered. [11][12][13] In all cases, muscle MRI can be used as a noninvasive test to detect mild muscle involvement, and a whole exome may be requested in some cases, as in ours, because of institutional characteristics.…”

“…Glycogenolysis and glycolysis are important during short exercise, and disorders of these pathways can manifest in 2 main presentation forms: as initial effort intolerance, myalgia, postexertional myoglobinuria, and episodes of CK increase as in McArdle disease (GSD type 5) and Tarui disease (GSD type 7), or presenting with progressive proximal muscle weakness associated with respiratory insufficiency as in lateonset Pompe disease (GSD type 2). 12 These 3 diseases are the most common disorders of carbohydrate metabolism in clinical practice.…”

Muscle biopsy: what and why and when?

“…Their workup often includes a gene panel for rhabdomyolysis and metabolic disorders—their clinical features are described elsewhere (see further reading). 24 26 Some myopathies that cause non-traumatic exertional rhabdomyolysis are not included in such a panel, for example, muscle dystrophies (case 2), ryanodine receptor myopathies and mitochondrial disorders. 27–29 Clinicians should seek relevant clinical clues when reviewing patients following their crisis.…”

“…This group includes the metabolic myopathies: their clinical features and workup are described elsewhere. 26 Remember that the metabolic gene panel is not exhaustive; if the panel is negative but clinical suspicion remains then a muscle biopsy may reveal, for example, a mutation in cytochrome b, the only mtDNA-encoded gene in complex III. 45…”