Mitochondrial trifunctional protein deficiency: an adult patient with similar progress to Charcot-Marie-Tooth disease
Open Access
- 1 January 2017
- journal article
- Published by Societas Neurologica Japonica in Rinsho Shinkeigaku
- Vol. 57 (2), 82-87
- https://doi.org/10.5692/clinicalneurol.cn-000976
Abstract
A 45-year-old man presented to us due to slowly progressive muscle weakness and sensory disturbances in his lower limbs since his 40's. He reported multiple episodes of exercise-induced severe muscle fatigue and brown urine in his childhood, which disappeared by age 20. A nerve conduction study showed peripheral axonal neuropathy and then Charcot-Marie-Tooth disease (CMT) was considered as the most likely diagnosis; however, exome sequencing failed to identify a mutation in the known genes of CMTs. Since age 55, he recurrently developed severe rhabdomyolysis that required hospitalization. On suspicion of lipid metabolism disorders, we performed serum acylcarnitine analysis, and which revealed mildly elevated long-chain fatty acids. We re-examined variants obtained via exome sequencing and found a mutation in HADHB. Mitochondrial trifunctional protein (MTP) deficiency is a rare autosomal recessive disorder of mitochondrial fatty acid beta-oxidation caused by HADHA or HADHB mutation. It can be a life-threatening multiorgan disorder with early infantile onset, but it can also present in childhood or adolescence with peripheral neuropathy and recurrent rhabdomyolysis. This case of adult-diagnosed MTP deficiency was characterized by slowly progressive peripheral neuropathy masquerading CMT in addition to muscular symptoms. MTP deficiency should be considered in patients with the combination of peripheral neuropathy and recurrent rhabdomyolysis.Keywords
This publication has 14 references indexed in Scilit:
- Mitochondrial trifunctional protein deficiency: A rare cause of adult-onset rhabdomyolysisMuscle & Nerve, 2013
- A patient with mitochondrial trifunctional protein deficiency due to the mutations in the HADHB gene showed recurrent myalgia since early childhood and was diagnosed in adolescenceMolecular Genetics and Metabolism, 2011
- Comprehensive cDNA study and quantitative analysis of mutant HADHA and HADHB transcripts in a French cohort of 52 patients with mitochondrial trifunctional protein deficiencyMolecular Genetics and Metabolism, 2011
- A Diagnostic Algorithm for Metabolic MyopathiesCurrent Neurology and Neuroscience Reports, 2010
- Diagnosis, natural history, and management of Charcot–Marie–Tooth diseaseThe Lancet Neurology, 2009
- Peripheral neuropathy, episodic myoglobinuria, and respiratory failure in deficiency of the mitochondrial trifunctional proteinMuscle & Nerve, 2003
- Mitochondrial trifunctional protein deficiency: A severe fatty acid oxidation disorder with cardiac and neurologic involvementThe Journal of Pediatrics, 2003
- Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to ?-subunit mutationsHuman Mutation, 2003
- Mild trifunctional protein deficiency is associated with progressive neuropathy and myopathy and suggests a novel genotype-phenotype correlation.JCI Insight, 1998
- Mitochondrial trifunctional protein deficiency associated with recurrent myoglobinuria in adolescenceNeurology, 1997