- An insight into the biochemistry of inborn errors of metabolism for a clinical neurologist

Inherited metabolic disorders presenting as myopathy are generally the result of defects in energy metabolism.[22] They consist of the following three categories: progressive muscle weakness, exercise intolerance with cramps and myoglobinuria and myopathy as a manifestation of multisystem disease.

Progressive muscle weakness is a characteristic feature in Pompe disease (Glycogen storage disorder (GSD) II). Progressive skeletal myopathy, occasionally involving the heart, may be a major problem in patients with Cori/Forbes disease (GSD III). Exercise intolerance with or without myoglobinuria is typical of a number of inherited defects of glycolysis, such as muscle phosphofructokinase deficiency (GSD VII), carnitine palmitoyl transferase II (CPT II) defect, myoadenylate deaminase deficiency, long-chain acyl-coenzyme A (CoA) dehydrogenase (LCAD) and short-chain hydroxyacyl-CoA dehydrogenase (SCHAD) defects. The biochemical differentiation of these defects is given in [Table 3]. The ischemic forearm exercise test is useful in the evaluation of these patients.[23] This test investigates the production of muscle energy through anaerobic glycolysis and the activation of the purine nucleotide cycle, which involves irreversible deamination of adenosine-5′-monophosphate (AMP) to inosine-5′-monophosphate (IMP), with ammonia production.

Progressive myopathy is also often the principal manifestation of mitochondrial electron transport chain defects, although other systems are invariably involved. Most are associated with persistent lactic acidosis, although lactate levels are generally not more than 10 mmol/l except during acute metabolic decompensation.

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