Carnitine palmitoyl transferase (CPT) deficiency. CPT II (adult & infantile myopathic form),
Incidence
More than 50 cases have been reported. It is AR inheritance, but more males have been reported. Recent molecular studies have demostrated a missense mutation converting a serine to leucine at position 113 (Ser113Leu) in more than 50% of patients.
Clinical Characteristics
Clinical presentation is a myopathic form (the most common cause of hereditary myoglobinuria). Normal life expectancy. Recurrent myoglobinuria precipitated by fasting or by prolonged but not necessarily strenous exercise or physical activity. Short-term intense exercise is well tolerated but not prolonged mild-moderate exercise. There is no "second-wind" phenomena. Carnitine levels are normal in muscle and serum. CPT is decreased in muscle, liver & fibroblasts. Usually no lipid storage in muscle seen. Severe attacks of muscle necrosis may cause respiratory weakness, renal failure and death. Between episodes pts. are normal. Very high CPK (> 20.000 IU) during crisis. Abn. EMG & sometimes abn. EKG during crisis. There is no ketotic response to fasting, but acute metabolic decompensation in older patients is rare.
Precipitants
Fasting and physical activity or exercise trigger symptoms. Also intercurrent infections, cold exposure or emotional stress.
Provocation Tests
The ischemic forearm exercise test produce normal lactate and ammonium responses but increased CPK.
Diagnostic Procedures
EB-F, EB-muscle, EB-liver. Many have a lipid storage myopathy. Very high CPK (> 20.000 IU) during crisis. Mutations have been identified in this condition. These can now be detected in DNA isolated from the blood. This analysis provides a practical alternative to muscle biopsy for initial screening.