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

Abstract

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 ADCK1 (p.Asn280fs), a gene related to mitochondrial function, which was confirmed using cDNA sequencing. ADCK1 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 ADCK1 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 ADCK1 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.