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Variability of Phenotype in Two Sisters with Pyridoxine Dependent Epilepsy

Published online by Cambridge University Press:  02 December 2014

Majid Alfadhel ,
Sandra Sirrs ,
Paula J. Waters ,
András Szeitz ,
Eduard Struys ,
Marion Coulter-Mackie  and
Sylvia Stockler-Ipsiroglu
Majid Alfadhel*
Affiliation:
Division of Biochemical Diseases, Department of Paediatrics, BC Children's and Women's Hospital Division of Genetics, Department of Pediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Sandra Sirrs
Affiliation:
Adult Metabolic Diseases Clinic, Division of Endocrinology, Department of Medicine, Vancouver Hospital and Health Sciences Centre
Paula J. Waters
Affiliation:
Biochemical Genetics Laboratory, University of British Columbia, Vancouver, British Columbia Service de Génétique Médicale, Département de Pédiatrie, Université de Sherbrooke, Quebec, Canada
András Szeitz
Affiliation:
Department of Pathology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia
Eduard Struys
Affiliation:
VU University Medical Centre, Metabolic Unit, Department of Clinical Chemistry, Amsterdam, Netherlands
Marion Coulter-Mackie
Affiliation:
Division of Biochemical Diseases, Department of Paediatrics, BC Children's and Women's Hospital
Sylvia Stockler-Ipsiroglu
Affiliation:
Division of Biochemical Diseases, Department of Paediatrics, BC Children's and Women's Hospital
*
Division of Genetics, Department of Pediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia, P.O. Box: 22490 Riyadh 11426. Email: dralfadhel@yahoo.com
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Abstract

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Background:

Pyridoxine dependent epilepsy (PDE) is characterized by neonatal epileptic encepahalopathy responsive to pharmacological doses of vitamin B6. Recently an autosomal recessive deficiency in Antiquitin (ALDH7A1), a gene involved in the catabolism of lysine has been identified as the underlying cause.

Case report:

In 21 and 23 year-old sisters, who had presented with neonatal / early infantile onset seizures, PDE was confirmed by elevated urinary alpha aminoadipic- 6- semialdehyde (α-AASA) excretion and compound heterozygosity for two known ALDH7A1 missense mutations. Although epilepsy was well controlled upon treatment with pyridoxine, thiamine, phenytoin and carbamazepine since early infancy, both had developmental delay with prominent speech delay as children. As adults, despite the same genetic background and early treatment with pyridoxine, their degree of intellectual disability (ID) differed widely. While the older sister's cognitive functions were in the moderate ID range and she was not able to live unattended, the younger sister had only mild ID and was able to live independently.

Conclusion:

Although seizures are a defining feature of PDE, other disease manifestations can vary widely even within the same family. Adult neurologists should be aware that the diagnosis of PDE can be delayed and PDE should be considered in the differential diagnosis of adults with seizure disorders dating from childhood.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 39 , Issue 4 , July 2012 , pp. 516 - 519
Copyright
Copyright © The Canadian Journal of Neurological 2012

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