Pyridoxine Dependent Epilepsy with ALDH7A1 Mutation: Clinical Spectrum and Outcome in A Multicenter Study Cohort From Turkey

Objective To describe the clinical characteristics of Turkish children with Pyridoxine-dependent epilepsy related to ALDH7A1 (PDE-ALDH7A1) as well as possible genotype–phenotype relationship.

Methods The study design was a multicentric, retrospective data-recording research. Demographic, clinical, and genetics data of 41 patients (23 male) with PDE-ALDH7A1 obtained from 15 Pediatric Neurology Centers in Turkey. Results The age of patients range was 9-215 months (mean:78 months). The age of onset of seizure was between 1-10 days in classical form (n:38) and 6-15 months in atypical form (n:3). Homozygous mutations were detected in 38 patients and compound heterozygous mutations in three patients. Mutation analysis identified 17 different ALDH7A1 mutations which six were novel. The majority of patients (58.5%) had homozygous mutation c.1597_1597delG in ALDH7A1gene. Different types of seizures were observed and focal motor and myoclonic seizures were the dominant types.Twenty of the 41 patients (54%) were seizure-free after only pyridoxine or pyridoxal phosphate treatment. However 18(44%) patients continued to take additional antiepileptic treatment and eight of them continued to have EEG abnormality. Mild to moderate psychomotor retardation was detected in 25(60%) of the cases.

Conclusion

The most common ALDH7A1 mutation in Turkey was found to be homozygous c.1597_1597delG. The present study supporting the literatüre that Turkish children with ALDH7A1 pathogenic variants usually had classical phenotypes. However, It is difficult to know whether this is because PDE-ALDH7A1 is considered more frequently in neonatal seizures or because the atypical form is less common.Every clinician should be aware of the significant phenotypic heterogeneity in this disease.