A novel frameshift mutation in ADCK1 identified in a case of chronic fatigue syndrome successfully treated with oral 5-ALA/SFC

Chronic Fatigue Syndrome (CFS) is a complex disorder characterized by prolonged, unexplained fatigue and challenging diagnosis. We report the case of a 35-year-old Japanese woman with CFS who had experienced chronic fatigue since the age of 11 years. Despite treatment with modafinil, methylphenidate, levocarnitine, and ubiquinone, the symptoms persisted. Introduction of oral 5-aminolevulinic acid with sodium ferrous citrate (5-ALA/SFC) led to significant improvements in daily activities, mobility, and psychosocial functioning. Genetic analysis revealed a novel heterozygous frameshift deletion in <i>ADCK1</i> (p.Asn280fs), a gene related to mitochondrial function, which was confirmed using cDNA sequencing. <i>ADCK1</i> deficiency has been associated with developmental disabilities, mitochondrial dysfunction, increased reactive oxygen species levels, and apoptosis in Drosophila and muscle cells. This case supports the hypothesis that <i>ADCK1</i> mutations contribute to mitochondrial dysfunction and CFS pathogenesis. The patient's significant clinical improvement with 5-ALA/SFC and ubiquinone suggests their potential for addressing mitochondrial dysfunction. Further functional and familial analyses are required to confirm the role of this heterozygous <i>ADCK1</i> mutation in CFS. This case highlights the importance of considering mitochondrial dysfunction in CFS, and the potential therapeutic benefits of 5-ALA/SFC and ubiquinone.