Mitochondrial trifunctional protein deficiency: A rare cause of adult‐onset rhabdomyolysis

Abstract

Mitochondrial trifunctional protein deficiency is a rare autosomal recessive disorder of mitochondrial fatty acid β-oxidation that may be due to mutations in 2 different nuclear genes, HADHA and HADHB. Perturbation of this multienzyme complex compromises the oxidation of long-chain fatty acids, which leads to multiorgan dysfunction. Childhood- or adolescent-onset recurrent rhabdomyolysis is a common muscular manifestation and is preceded frequently by clinically overt peripheral neuropathy. In this report we describe a patient with late adult-onset recurrent rhabdomyolysis. Despite normal sensory examination, nerve conduction studies showed a mild axonal peripheral neuropathy. The acylcarnitine profile showed elevated long-chain and 3-hydroxy long-chain acylcarnitine species. HADHA sequencing revealed known compound heterozygous mutations c.180+3A>G (p.Thr37SerfsX6) and c.1528G>C (p.Glu510Gln). During a 10-month follow-up period, he had no further episodes of rhabdomyolysis after appropriate dietary modifications. Mitochondrial trifunctional protein deficiency should be considered in patients with adult-onset recurrent rhabdomyolysis, especially in those with either clinically overt or subclinical peripheral neuropathy.