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 beta-oxidation cycle with heterogeneous phenotypes and occurs secondary to either alpha- or beta-subunit mutations. We characterized the neuromyopathic phenotype of TFP deficiency through adolescence or adulthood in 11 patients, 8 with beta-subunit mutations and 3 with alpha-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.
Spiekerkoetter
Ute
U
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. ute.spiekerkoetter@uni-duesseldorf.de
Bennett
Michael J
MJ
Ben-Zeev
Bruria
B
Strauss
Arnold W
AW
Tein
Ingrid
I
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004281:Docosahexaenoic Acids / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D028361:Mitochondrial Diseases / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000172:deficiency* / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D009212:Myoglobinuria / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D009431:Neural Conduction / Q000502:physiology; D009468:Neuromuscular Diseases / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012131:Respiratory Insufficiency / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D012206:Rhabdomyolysis / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D013256:Steroids / Q000627:therapeutic use; D016896:Treatment Outcome
D009097:Multienzyme Complexes; D021122:Protein Subunits; D013256:Steroids; D004281:Docosahexaenoic Acids; D063991:Mitochondrial Trifunctional Protein