Periodic Paralysis in a Child With Thermosensitive Mitochondrial Trifunctional Protein Deficiency

Mitochondrial trifunctional protein (MTP) deficiency is a fatty acid oxidation disorder associated with a spectrum of phenotypes. Patients with high residual enzyme activity tend to have milder phenotypes, and recently, fever-induced episodic myopathy was reported in association with a thermosensitive form of MTP deficiency. We report a 10-year-old male with recurrent episodes of acute flaccid paralysis involving upper and lower extremities in association with bulbar muscle weakness in the context of febrile illness, a phenotype reminiscent of recurrent periodic paralysis. The episodes started at the age of 3 years and have always been followed by full recovery within 1-2 weeks with no residual weakness. Whole exome sequencing revealed a homozygous c.2132C > T, p.(Pro711Leu) variant in HADHA. The variant leads to mildly reduced long-chain hydroxyacyl-CoA dehydrogenase (LCHAD) and long-chain ketoacyl-CoA thiolase (LCKAT) enzyme activities and reduced MTP protein expression in patient's fibroblasts when cultured at 37°C. Enzyme activities and MTP protein expression diminished when fibroblasts were cultured at 40°C. This is the first published report of confirmed recurrent periodic paralysis as a manifestation of a thermosensitive form of MTP deficiency, and it calls for this condition to be considered when evaluating patients with recurrent periodic paralysis given therapeutic implications.