Follow-up of folinic acid supplementation for patients with cerebral folate deficiency and Kearns-Sayre syndrome
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RESEARCH
Open Access
Follow-up of folinic acid supplementation for patients with cerebral folate deficiency and Kearns-Sayre syndrome Pilar Quijada-Fraile1, Mar O’Callaghan3, Elena Martín-Hernández1, Raquel Montero2,3, Àngels Garcia-Cazorla2,3, Ana Martínez de Aragón1, Jordi Muchart3, Ignacio Málaga4, Rafael Pardo5, Pedro García-Gonzalez5, Cristina Jou3, Julio Montoya2,6, Sonia Emperador6, Eduardo Ruiz-Pesini2,6, Joaquín Arenas2,7, Miguel Angel Martin2,7, Aida Ormazabal2,3, Mercè Pineda2,3, María T García-Silva1,2 and Rafael Artuch2,3*
Abstract Background: 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. Methods: 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. Results: 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. (Continued on next page)
* Correspondence: [email protected] 2 Centre For research in rare diseases (CIBERER), Institut de Salud Carlos III, Madrid, Spain 3 Pediatric Neurology, Clinical Biochemistry, Histopathology and Radiology Departments, Hospital Sant Joan de Déu, Passeig Sant Joan de Déu, 2., Esplugues, Barcelona 08950, Spain Full list of author information is available at the end of the article © 2014 Quijada-Fraile et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License
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