Kearns-Sayre syndrome (KSS) is a mitochondrial DNA deletion syndrome that presents with profound cerebral folate deficiency and other features. Preliminary data support the notion that folinic acid therapy might be useful in the treatment of KSS patients. Our aim was to assess the clinical and neuroimaging outcomes of KSS patients receiving folinic acid therapy.
Patients: We recruited eight patients with diagnoses of KSS. Four cases were treated at 12 de Octubre Hospital, and the other two cases were treated at Sant Joan de Déu Hospital. Two patients refused to participate in the treatment protocol.
Methods: Clinical, biochemical and neuroimaging data (magnetic resonance imaging or computed tomography scan) were collected in baseline conditions and at different time points after the initiation of therapy. Cerebrospinal fluid 5-methyltetrahydrofolate levels were analysed with HPLC and fluorescence detection. Large-scale mitochondrial DNA deletions were analysed by Southern blot.
Treatment protocol: The follow-up periods ranged from one to eight years. Cases 1–4 received oral folinic acid at a dose of 1 mg/kg/day, and cases 6 and 8 received 3 mg/kg/day.
No adverse effects of folinic acid treatment were observed. Cerebral 5-methyltetrahydrofolate deficiencies were observed in all cases in the baseline conditions. Moreover, all three patients who accepted lumbar puncture after folinic acid therapy exhibited complete recoveries of their decreased basal cerebrospinal fluid 5-methyltetrahydrofolate levels to normal values. Two cases neurologically improved after folinic therapy. Disease worsened in the other patients.
Post-treatment neuroimaging was performed for the 6 cases that received folinic acid therapy. One patient exhibited improvements in white matter abnormalities. The remaining patients displayed progressions in subcortical cerebral white matter, the cerebellum and cerebral atrophy.
Four patients exhibited clinical and radiological progression of the disease following folinic acid treatment. Only one patient who was treated in an early stage of the disease exhibited both neurological and radiological improvements following elevated doses of folinic acid, and an additional patient experienced neurological improvement. Early treatment with high-dose folinic acid therapy seems to be advisable for the treatment of KSS.
Electronic supplementary material
The online version of this article (doi:10.1186/s13023-014-0217-2) contains supplementary material, which is available to authorized users.