A novel frameshift mutation in ADCK1 identified in a case of chronic fatigue syndrome successfully treated with oral 5-ALA/SFC.
Koga, Tomohiro, Kita, Kiyoshi, Okumura, Junko et al. · Immunological medicine · 2025 · DOI
Quick Summary
This study reports a single patient with ME/CFS who carried a rare genetic mutation affecting how cells produce energy. When treated with a supplement called 5-ALA/SFC along with other nutrients, the patient's fatigue and daily functioning significantly improved. This case suggests that some people with ME/CFS may have mitochondrial (cellular energy) problems related to this genetic change, and that certain supplements might help.
Why It Matters
This case supports the growing evidence that mitochondrial dysfunction may underlie ME/CFS in at least some patients, providing a testable biological mechanism. If confirmed in larger cohorts, genetic screening for ADCK1 mutations and targeted mitochondrial therapies could improve diagnostic precision and treatment options for ME/CFS patients who have not responded to standard care.
Observed Findings
A 35-year-old woman with ME/CFS since age 11 carried a novel heterozygous frameshift deletion in ADCK1 (p.Asn280fs).
Treatment with 5-ALA/SFC combined with ubiquinone led to significant improvements in daily activities, mobility, and psychosocial functioning.
Prior treatments with modafinil, methylphenidate, levocarnitine, and ubiquinone alone did not resolve symptoms.
Genetic analysis confirmed the frameshift mutation using cDNA sequencing.
Inferred Conclusions
ADCK1 mutations may contribute to mitochondrial dysfunction and could be involved in ME/CFS pathogenesis in some patients.
5-ALA/SFC and ubiquinone show potential therapeutic benefit for addressing mitochondrial dysfunction in ME/CFS.
Mitochondrial dysfunction should be considered as a possible biological mechanism in ME/CFS evaluation and treatment.
Remaining Questions
Does this ADCK1 variant segregate in the patient's family, and is it inherited or de novo?
What is the functional consequence of this specific frameshift mutation on ADCK1 protein and mitochondrial function?
Will 5-ALA/SFC be similarly effective in other ME/CFS patients, and which patients might benefit most?
What This Study Does Not Prove
This is a single case report and does not prove that ADCK1 mutations cause ME/CFS or that 5-ALA/SFC will help all ME/CFS patients. The study cannot establish whether the mutation was directly responsible for this patient's illness, whether the genetic variant was inherited or de novo, or whether the clinical improvement was solely attributable to the new treatment. The findings cannot be generalized beyond this individual.
Tags
Symptom:Fatigue
Biomarker:Gene ExpressionBlood Biomarker
Phenotype:Gradual Onset
Method Flag:PEM Not DefinedNo ControlsSmall SampleExploratory Only