[Metabolic intolerance to exercise].
Exercise intolerance (EI) is a frequent cause of medical attention, although it is sometimes difficult to come to a final diagnosis. However, there is a group of patients in whom EI is due to a metabolic dysfunction. McArdle's disease (type V glucogenosis) is due to myophosphorylase (MPL) deficiency. The ischemic exercise test shows a flat lactate curve. The most frequent mutations in the PYGM gene (MPL gene) in Spanish patients with MPL deficiency are R49X and W797R. Carnitine palmitoyltransferase (CPT) II deficiency is invariably associated to repetitive episodes of myoglobinuria triggered by exercise, cold, fever or fasting. The diagnosis depends on the demonstration of CPT II deficiency in muscle. The most frequent mutation in the CPT2 gene is the S113L. Patients with muscle adenylate deaminase deficiency usually show either a mild myopathy or no symptom. The diagnosis is based on the absence of enzyme activity in muscle and the lack of rise of ammonia in the forearm ischemic exercise test. The mutation Q12X in the AMPD1 gene is strongly associated with the disease. Exercise intolerance is a common complaint in patients with mitochondrial respiratory chain (MRC) deficiencies, although it is often overshadowed by other symptoms and signs. Only recently we have come to appreciate that exercise intolerance can be the sole presentation of defects in the mtDNA, particularly in complex I, complex III, complex IV, or in some tRNAs. In addition, myoglobinuria can be observed in patients under statin treatment, particularly if associated with fibrates, due to an alteration in the assembly of the complex IV of the MRC.
Arenas
J
J
Laboratorio de enfermedades mitocondriales y nurometabólicas, Centro de Investigación Hospital Universitario 12 de Octubre, Madrid, Spain. jarenas@h12o.es
Martín
M A
MA
D000243:Adenosine Deaminase / Q000172:deficiency; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency; D015444:Exercise / Q000502:physiology*; D017079:Exercise Tolerance / Q000502:physiology*; D006012:Glycogen Storage Disease Type V / Q000503:physiopathology; D006801:Humans; D008929:Mitochondria, Heart / Q000502:physiology
D002334:Carnitine O-Palmitoyltransferase; D000243:Adenosine Deaminase