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