Pyridoxine-dependent seizures: a family phenotype that leads to severe cognitive deficits, regardless of treatment regime.
The neuropsychological and clinical histories of three male siblings affected by pyridoxine-dependent seizures with known homozygous antiquitin mutations are presented. Neuropsychological evaluation is reported from when the siblings were 11, 9, and 7 years of age. Two of the siblings had received early pyridoxine treatment (antenatal, 2-4 wks into pregnancy) and one had received late treatment (2mo postnatal). However, there was no differential effect on cognitive outcome, with all three siblings having moderate to severe learning disability. Unlike previously reported cases that received early postnatal treatment, none of the siblings had relatively preserved non-verbal cognitive skills. Equally, their intellectual performance over time did not increase above the 1st centile despite high maintenance doses of vitamin B6 (range 16-26 mg/kg/d), and mild sensory neuropathy was reported on nerve conduction studies. The findings in these siblings challenge assumptions that early and high dose pyridoxine treatment can benefit cognition in this population and suggest routine electromyography monitoring may be beneficial.
Rankin
Peter M
PM
Developmental Cognitive Neuroscience Unit, Institute of Child Health, University College London, UK. p.rankin@ich.ucl.ac.uk
Harrison
Sue
S
Chong
W K
WK
Boyd
Stewart
S
Aylett
Sarah E
SE
D000284:Administration, Oral; D000293:Adolescent; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000927:Anticonvulsants / Q000008:administration & dosage*; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003337:Corpus Callosum / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance / Q000235:genetics; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D004829:Epilepsy, Generalized / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008607:Intellectual Disability / Q000188:drug therapy / Q000235:genetics*; D007360:Intelligence / Q000187:drug effects / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009460:Neurologic Examination / Q000187:drug effects; D009483:Neuropsychological Tests; D010641:Phenotype; D011247:Pregnancy; D011736:Pyridoxine / Q000008:administration & dosage*
D000927:Anticonvulsants; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; D011736:Pyridoxine