El ácido folínico no es eficaz en el tratamiento del síndrome de Kearns-Sayre

It was with great interest that we read the case presented by Pardo Ruiz et al.1 of an 8-year-old patient with KearnsSayre syndrome (KSS), with a single 6.4-kb mitochondrial DNA (mtDNA) deletion and a heteroplasmy rate of 27%. We would like to make the following observations. Mitochondrial DNA deletions are rarely inherited.2 Did the patient’s mother present symptoms of mitochondrial disease? Did she undergo studies aimed at detecting mtDNA deletions? A heteroplasmy rate of 27% is low, and unlikely to fully explain the patient’s severe, progressive phenotype. Although muscle biopsy was not performed, we wonder whether the heteroplasmy rate was determined in other tissues, particularly in muscle tissue, where the rate is usually higher. There are several possible explanations for the ineffectiveness of folinic acid. Firstly, the dose may have been too low. The authors do not indicate the daily dose administered to the patient, treatment duration, or whether the dose changed during the treatment period. Secondly, folinic acid is unable to cross the blood—brain barrier. Were CSF folinic acid levels determined at the end of the treatment period? Third, the ineffectiveness of the treatment may be explained by malabsorption of oral folinic acid. Did the patient have any gastrointestinal diseases that may have interfered with drug absorption? Patients with mitochondrial diseases frequently display such gastrointestinal manifestations as gastroesophageal sphincter dysfunction, constipation, dysphagia, vomiting, gastroparesis, gastrointestinal pseudo-obstruction, diarrhoea, and pancreatitis.3 Were folinic acid levels determined before and after treatment? Furthermore, treatment adherence may have been poor. Did the patient’s carers supervise medication? Although treatment had no clinical effect, it may have had a subclinical effect, reducing the heteroplasmy rate. Was the heteroplasmy rate determined before and after treatment?