Leman Tekin Orgun, İlknur Erol, Seda Kanmaz, Şeyda Beşen, Cengiz Havalı, Habibe Koç Uçar, Canan Yıldırım, Erdem Şimşek, Pakize Karaoğlu, Türkan Uygur Şahin, Ayşe Aksoy, Faruk İncecik, Gülen Gül Mert, Gül Demet Kaya, Mehbare Özkan, Pınar Özkan, Senem Ayça, Tuğçe Uzunhan, Fatma Derya Bulut, Elif Perihan Öncel, Sevcan Tuğ Bozdoğan, Sanem Keskin, Hasan Tekgül

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.
Keywords: Epilepsy, ALDH7A1 ,gene, mutation, pyridoxine

Leman Tekin Orgun
Başkent University Medical Faculty, Turkey
Turkey

İlknur Erol
Başkent University Medical Faculty, Turkey
Turkey

Seda Kanmaz
Ege University Medical Faculty, Turkey
Turkey

Şeyda Beşen
Başkent University Medical Faculty, Turkey
Turkey

Cengiz Havalı
Bursa Yuksek İhtisas Training and Research Hospital, Turkey
Turkey

Habibe Koç Uçar
Adana Training and Research Hospital, Turkey
Turkey

Canan Yıldırım
Okan University Medical Faculty, Turkey
Turkey

Erdem Şimşek
Hatay State Hospital, Turkey
Turkey

Pakize Karaoğlu
Dr. Behcet Uz Children's Hospital, Turkey
Turkey

Türkan Uygur Şahin
Bezmi Alem Vakıf University Medical Faculty, Turkey
Turkey