Şeyda Beşen, İlknur Erol , Özlem Sangün, Leman Tekin Orgun, Atıl Bişgin

Objectives Hyperphosphatasia mental retardation syndrome(HPMRS) is a rare,autosomal recessive disease.It is caused by homozygous or compound heterozygous mutations of six genes (PIGV,PIGY,PIGO,PGAP2,PIGW and PGAP3) which involved in phosphatidylinositol biosynthesis.Depending on the mutated gene,it is divided into six subtypes as HPMRS types 1-6.All subtypes have common clinical features:dysmorphic facial findings,severe mental motor retardation (MMR),hypotonia and persistent alkaline phosphatase(ALP) elevation.The associated congenital anomalies differ between types.HPMRS type 4 is caused by mutations in the PGAP3 gene and is accompanied by epilepsy.There are nearly 30 HPMRS type 4 cases in the literature and only two of which are Turkish. Methods Herein the largest series from Turkey diagnosed with PGAP3-associated HPMRS type 4 whose epileptic seizures responded to pyridoxine are reported. Results All four HPMRS type 4 cases,two of which were siblings,had significant dysmorphic features,mental retardation,epilepsy,elevated alkaline phosphatase levels and hypotonia.The age of patients ranged from 10 months to 12 years and 6 months,all cases had epilepsy and one had drug resistant epilepsy,who was applied a vagal nerve stimulator in an another tertitory center.In addition to the antiepileptic drug treatment,all cases was started with pyridoxine,considering the pathophysiological mechanisms after the underlying genetic diagnosis.Seizure control was achieved in all cases. Conclusion: Identifying the underlying genetic mutations and mechanisms will open new horizons in the control of diseases with specific targeted therapies,as in our cases.In this study, pyridoxine response in epilepsy of HPMRS type 4 cases was shown for the first time in the literature.

Keywords: HPMRS type 4,hyperphosphatasia,hypotonia,PGAP3,mental retardation

Şeyda Beşen
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

İlknur Erol
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

Özlem Sangün
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

Leman Tekin Orgun
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

Atıl Bişgin
Cukurova University AGENTEM (Adana Genetic Diseases Diagnosis and Treatment Center) and Medical Genetics Department of Medical Faculty
Turkey