Thursday, June 8, 2023
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Purpose of review: The present review will focus on the clinical features, and recent advances in the investigation and treatment, of metabolic
muscle disease. The aim is to present a summary of this vast and complex topic emphasizing key points of relevance to nonspecialists
in the field. Salient examples from each category will be highlighted to illustrate characteristic features and potential
sources of diagnostic confusion. The general approach to management will then be outlined.
Recent findings: Awareness of these diseases has grown over recent years, as has appreciation of their variable clinical presentation. Many
of the precise genetic and biochemical abnormalities underlying these conditions have been elucidated and novel enzyme defects
continue to be discovered. Perhaps the greatest progress, however, has been made in the management of disease. Advances in
tandem mass spectrometry techniques have facilitated the introduction of nationwide neonatal screening programmes for a large
number of metabolic disorders. Enzyme replacement in Pompe disease has proved successful, improving outcome in a hitherto
untreatable condition. Progress towards gene therapy, perhaps the ultimate goal, has been made in animal models.
Summary: Although individually rare, the metabolic myopathies together constitute a significant group of disabling and potentially
life-threatening disorders. Appropriate investigations, timely treatment and genetic counselling are paramount to ameliorate
the short and long-term consequences of disease.
Abnormalities of skeletal muscle energy production characterize the varied group of disorders known as the metabolic myopathies. These arise as a consequence of inherited defects in glycogen, lipid or purine metabolism, or hereditary abnormalities of the mitochondrial electron transport chain. Although traditionally managed by neurologists, it is imperative that all clinicians are aware of the metabolic myopathies as they may mimic other conditions, can be life threatening and are potentially treatable. This review will summarize the clinical features that should prompt consideration of metabolic muscle disease highlighting examples from each category. Mitochondrial myopathies will only briefly be mentioned as they have been recently reviewed in the journal.[1]
Metabolic myopathies typically present with episodes of reversible muscle dysfunction induced by exercise. Features include muscle weakness, cramp, pain, stiffness and myoglobinuria. Less frequently they manifest as persistent, progressive muscle weakness. Whereas severe extramuscular manifestations are common in children, disease emerging in later life primarily affects muscles.[2]
Most metabolic myopathies arise due to enzymatic defects causing impaired muscle ATP production. A familiarity with muscle energy metabolism is, therefore, fundamental to understanding their pathogenesis.
