Clinical, biochemical and molecular characterization of a new case with FDX2-related mitochondrial disorder: Potential biomarkers and treatment options

Ferredoxin-2 (FDX2) is an electron transport protein required for iron-sulfur clusters biosynthesis. Pathogenic variants in FDX2 have been associated with autosomal recessive FDX2-related disorder characterized by mitochondrial myopathy with or without optic atrophy and leukoencephalopathy. We described a new case harboring compound heterozygous variants in FDX2 who presented with recurrent rhabdomyolysis with severe episodes affecting respiratory muscle. Biochemical analysis of the patients revealed hyperexcretion of 2-hydroxyadipic acid, along with previously reported biochemical abnormalities. The proband demonstrated increased lactate and creatine kinase (CK) with increased amount of glucose infusion. Lactate and CK drastically decreased when parenteral nutrition containing high protein and lipid contents with low glucose was initiated. Overall, we described a new case of FDX2-related disorder and compare clinical, biochemical and molecular findings with previously reported cases. We demonstrated that 2-hydroxyadipic acid biomarker could be used as an adjunct biomarker for FDX2-related disorder and the use of parenteral nutrition as a treatment option for the patient with FDX2-related disorder during rhabdomyolysis episode.

Highlights: 2-Hydroxyadipic acid can serve as a potential adjunct biomarker for iron-sulfur assembly defects and lipoic acid biosynthesis disorders. Parenteral nutrition containing high lipid and protein content could be used to reverse acute rhabdomyolysis episodes in the patients with FDX2-related disorder.