Peripheral neuropathy, episodic myoglobinuria, and respiratory failure in deficiency of the mitochondrial trifunctional protein

Mitochondrial trifunctional protein (TFP) deficiency is a rare disorder of the fatty acid β‐oxidation cycle with heterogeneous phenotypes and occurs secondary to either α‐ or β‐subunit mutations. We characterized the neuromyopathic phenotype of TFP deficiency through adolescence or adulthood in 11 patients, 8 with β‐subunit mutations and 3 with α‐subunit mutations. Two independent clinical features occurred: infantile‐onset progressive peripheral neuropathy and episodic exercise‐, illness‐ or fasting‐induced rhabdomyolysis accompanied by respiratory failure (in five patients). The combination of episodic rhabdomyolysis and peripheral neuropathy occurred in 10 of the 11 patients. The neuromyopathic phenotype is common in TFP deficiency (11 of 27 families from our cohort). Therefore, this disorder must be considered in the differential diagnosis of progressive peripheral neuropathy with or without episodic myoglobinuria. Muscle Nerve 29: 66–72, 2004