A Treatable Cause of Refractory Epilepsy: Pyridoxine-Dependent Epilepsy

Öz

Objective: Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder that typically presents with refractory seizures in infancy or early childhood. Seizures are resistant to conventional antiepileptic treatments and responsive to pharmacologic doses of pyridoxine. In this study, we aimed to present the clinical and genetic features of
six patients followed up in our clinic with PDE diagnosis.
Material and Methods: Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder that typically presents with refractory seizures in infancy or early childhood. Seizures are resistant to conventional antiepileptic treatments and responsive to pharmacologic doses of pyridoxine. In this study, we aimed to present the clinical and
genetic features of six patients followed up in our clinic with PDE diagnosis.
Results: Among six patients five were male and one was female. Mean age was 6.83 ± 3.71 years. The mean age of onset for seizures was 22.33 ± 31.77 (3-90 days). Seizures had started in the newborn period in all patients except one patient (n: 4). Three patients had focal motor seizures, 2 patients had generalized motor seizures and 1 patient had epileptic spasms. Vitamin B6 therapy was started in the early period except one patient. Mental retardation, stereotypic movements and autistic findings were observed in the all patients except one patient who had received early treatment. Molecular genetic analysis revealed 5 different mutations [homozygous c.1597delG (p.Ala533ProfsTer18) in 2 cases, homozygous c.781 A> G (p.Met261Val) in 1 case, compound heterozygous c.328C> T (p.Arg110Ter) / c.1566- 1G>T, 1 case heterozygous c.328C> T (p.Arg110Ter) and 1 case heterozygous c.1356 A> C (p.Lys452Asn) ] .

Conclusion: Pyridoxine-dependent epilepsy is a treatable cause of epilepsy and should come to mind in infants with unexplained refractory seizures. Treatment with a therapeutic dose of pyridoxine should be started promptly.

Anahtar Kelimeler

• Seizure
• Pyridoxine-dependent epilepsy
• Vitamin B6

Dirençli Epilepsinin Tedavi Edilebilir Bir Nedeni: Piridoksin Bağımlı Epilepsi

Öz

Amaç: Piridoksin bağımlı epilepsi, tipik olarak bebeklik veya erken çocukluk döneminde inatçı nöbetler ile seyreden nadir görülen otozomal resesif bir hastalıktır. Nöbetler geleneksel antiepileptik tedavilere dirençli olup, farmakolojik dozda piridoksine yanıt verir. Bu çalışmada PBE tanısı ile  izlediğimiz altı hastanın klinik ve genetik özelliklerini  sunmayı amaçladık.

Gereç ve Yöntemler: Ege Üniversitesi Tıp Fakültesi Çocuk Nöroloji Bilim Dalı’nda  Piridoksin bağımlı epilepsi tanısı ile izlenen altı olgunun klinik ve genetik özellikleri ile prognozu retrospektif olarak değerlendirildi.

Bulgular: Çalışmaya alınan hastaların 5’i erkek, 1’i kız olup, yaş ortalaması 6,83±3,71 yıl idi. Nöbet başlangıç yaşı ortalama 22,33± 31,77 (3-90gün) olup, bir hasta (n:4) hariç diğerleri yenidoğan döneminde başlamıştı. Üç hastada fokal motor nöbet, 2 hastada jeneralize motor nöbet ve 1 hastada epileptik spazm  izlendi. Hastaların vitamin B6 tedavisi bir hasta hariç erken dönemde başlandı. Erken dönem tedavi başlanan bir hasta dışında diğer hastalarda mental retardasyon, stereotipik hareketler ve otistik bulgular izlendi. Yapılan moleküler genetik analizde 5 farklı mutasyon saptanmıştır [2 olguda homozigot c.1597delG (p.Ala533ProfsTer18), 1 olguda homozigot c.781 A>G (p.Met261Val), 1 olguda birleşik heterozigot c.328C>T (p.Arg110Ter)/c.1566-1G>T, 1 olguda heterozigot c.328C>T (p.Arg110Ter) ve 1 olguda heterozigot c.1356 A>C (p.Lys452Asn)] .

Sonuç: PBE tedavi edilebilir epilepsi nedenlerinden biri olup açıklanamayan dirençli nöbetleri olan bebeklerde  mutlaka düşünülmeli ve terapotik dozda piridoksin tedavisine başlanmalıdır.

Anahtar Kelimeler

• Piridoksin bağımlı epilepsi
• ALDH7A1
• nöbet

Kaynakça

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