Abstract
BACKGROUND AND AIMS: Mitochondrial trifunctional protein deficiency (MTPD) is an inherited disorder of fatty acid β-oxidation caused by mutations in HADHA or HADHB genes. It typically presents with cardiomyopathy or hepatic failure in early childhood; however, it may rarely present in adulthood with the neuromyopathic form. METHODS: We describe a patient with MTPD with isolated neuropathy mimicking Charcot-Marie-Tooth disease (CMT) as the first and only presenting symptom. Clinical and electrophysiological examinations were conducted, including nerve conduction studies, needle electromyography, muscle and nerve biopsies. The diagnosis was confirmed with genetic testing and enzymatic analysis of cultured skin fibroblasts. RESULTS: We report a 40-year-old man diagnosed with axonal CMT2 in childhood. He had pes cavus and hammer toes, mild distal lower limb weakness, and loss of vibration sense with areflexia. He later developed fatigability, improved exercise tolerance with alcohol and an episode of chest infection causing neurological decompensation without evidence of rhabdomyolysis. Neurophysiology showed non-length-dependent axonal sensorimotor neuropathy without myopathic features. Genetic testing confirmed that he was compound heterozygous for two HADHA variants, one of them novel, and enzymatic analysis of cultured skin fibroblasts confirmed MTPD. INTERPRETATION: We report a very rare isolated neuropathic phenotype of MTPD and confirm the pathogenicity of the novel variant c.1003G>A, p.(Glu335Lys). This case also highlights the need for HADHA and HADHB to be included in neuropathy gene panels as MTPD may present as CMT. Given that dietary management may prevent some complications of MTPD, achieving a diagnosis early is important.