Developmental Profiles of Children with Pyridoxine-Dependent Epilepsy (PDE)

Background/Purpose: Most children with antiquitin deficiency become seizure free on pyridoxine. However, 75 to 80% develop mental retardation. Whether adjunctive treatments such as lysine-restricted diet and arginine supplementation will lead to better outcomes remains to be elucidated. We aimed to describe the developmental profiles in children with PDE.

Methods: Eleven patients (8 females, 3 males) were studied at a median age of 2.9 years (10 months to 15 years). All children were on pyridoxine, and six were additionally treated with a lysine-restricted diet. Age appropriate developmental tests (Bayley scales III in 6, WPSSI-III in 2, WISC-IV in 3) were applied in addition to a standardized questionnaire on behavior.

Results: In patients younger than 3 years, standardized testing of development showed normal development in two out of six. Motor development was delayed in three out of six, and speech development was delayed in four out of six. In patients older than 3 years, verbal IQ was below average in three out of five. Processing speed was impaired in all the five. Nine of 11 children showed oculomotor problems associated with squint, resulting in impaired visual fixation and pursuit. Visual field defects were noted in one. Except for the two youngest children, all had behavioral problems. A diagnosis of an autistic spectrum disorder was established in 2 out of 11.

Conclusion: Despite treatment according to current guidelines including pyridoxine and lysine-restricted diet, our survey confirms major developmental problems in children with PDE, with older children being especially affected. Besides well-known problems affecting speech development, a high proportion of our cohort showed impaired processing speed and oculomotor problems. To further study the effect of innovative treatments, a REDCap database has been established.