Variability of phenotype in two sisters with pyridoxine dependent epilepsy.
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.


METHODS
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.


CONCLUSIONS
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.
Department of Paediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia. dralfadhel@yahoo.com
Majid
M
Alfadhel
Sandra
S
Sirrs
Paula J
PJ
Waters
András
A
Szeitz
Eduard
E
Struys
Marion
M
Coulter-Mackie
Sylvia
S
Stockler-Ipsiroglu
D015074:2-Aminoadipic Acid / Q000031:analogs & derivatives / Q000172:deficiency / Q000652:urine; D018450:Disease Progression; D004827:Epilepsy / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology* / Q000652:urine; D005260:Female; D006801:Humans; D010641:Phenotype; D035781:Siblings; D055815:Young Adult
D015074:2-Aminoadipic Acid; C000061:allysine