Issue: Vojnosanit Pregl 2017; Vol. 74 (No. 6)

First patient in Serbia with biochemically and genetically diagnosed pyridoxine-dependent epilepsy

Authors:
Miloš M. Ješić, Maja D. Ješić, Svetlana Buljugić, Aleksandra Živanović

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Introduction. Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive inborn error of metabolism present with early-onset seizures resistant to common anticonvulsants. PDE has been shown to be caused by a defect of a α-aminoadipic semialdehyde dehydrogenase (also known as ALDH7A1 or antiquitin) in the cerebral lysine degradation pathway. Its deficiency results in accumulation of α-aminoadipic semialdehyde (α-AASA), piperideine -6-carboxylate and pipe-colic acid, which serve as diagnostic markers in urine, plasma and cerebrospinal fluid of the disease. α-Aminoadipic semialdehyde dehydrogenase is encoded by the ALDH7A1 or antiquitin gene and definite confirmation of diagnosis of PDE is made by genetic analysis. Case report. We present a first pa-tient in Serbia who was diagnosed clinically, biochemically and genetically. We suspected PDE due to drug-resistant seizures in the seventh day of life when we attempted with pyridoxine. Since that time the patient has taken pyridoxine and the seizu-res have not recured. Our patient had markedly elevated α-AASA in urine while on treatment with individual dosages of pyridoxine. Molecular-genetical analysis identified mutations of the ALDH7A1 (antiquitin) gene. Conclusion. α-AASA is reli-able marker to select PDF patient for molecular analysis of the ALDH7A1(antiquitin) gene. Diagnosis is confirmed by mole-cular-genetical analysis and pyridoxine withdrawal is no longer needed to establish the diagnosis of „definite“ PDE.