AIM: While there have been isolated reports of callosal morphology differences in pyridoxine-dependent epilepsy (PDE), a rare autosomal disorder caused by ALDH7A1 gene mutations, no study has systematically evaluated callosal features in a large sample of patients. This study sought to overcome this knowledge gap. METHOD: Spanning a wide age range from birth to 48 years, corpus callosum morphology and cross-sectional cerebral area were measured in 30 individuals with PDE (12 males, 18 females, median age 3.92y; 25th centile 0.27, 75th centile 15.25) compared to 30 age-matched comparison individuals (11 males, 19 females, median age 3.85y; 25th centile 0.26, 75th centile 16.00). Individuals with PDE were also divided into age groups to evaluate findings across development. As delay to treatment may modulate clinical severity, groups were stratified by treatment delay (less than or greater than 2wks from birth). RESULTS: Markedly reduced callosal area expressed as a ratio of mid-sagittal cerebral area was observed for the entire group with PDE (p<0.001). Stratifying by age (<1y, 1-10y, >10y) demonstrated posterior abnormalities to be a consistent feature, with anterior regions increasingly involved across the developmental trajectory. Splitting the PDE group by treatment lag did not reveal overall or sub-region callosal differences. INTERPRETATION: Callosal abnormalities are a common feature of PDE not explained by treatment lag. Future work utilizing tract-based approaches to understand inter- and intra-hemispheric connectivity patterns will help in the better understanding the structural aspects of this disease.
AIM: While there have been isolated reports of callosal morphology differences in pyridoxine-dependent epilepsy (PDE), a rare autosomal disorder caused by ALDH7A1 gene mutations, no study has systematically evaluated callosal features in a large sample of patients. This study sought to overcome this knowledge gap. METHOD: Spanning a wide age range from birth to 48 years, corpus callosum morphology and cross-sectional cerebral area were measured in 30 individuals with PDE (12 males, 18 females, median age 3.92y; 25th centile 0.27, 75th centile 15.25) compared to 30 age-matched comparison individuals (11 males, 19 females, median age 3.85y; 25th centile 0.26, 75th centile 16.00). Individuals with PDE were also divided into age groups to evaluate findings across development. As delay to treatment may modulate clinical severity, groups were stratified by treatment delay (less than or greater than 2wks from birth). RESULTS: Markedly reduced callosal area expressed as a ratio of mid-sagittal cerebral area was observed for the entire group with PDE (p<0.001). Stratifying by age (<1y, 1-10y, >10y) demonstrated posterior abnormalities to be a consistent feature, with anterior regions increasingly involved across the developmental trajectory. Splitting the PDE group by treatment lag did not reveal overall or sub-region callosal differences. INTERPRETATION:Callosal abnormalities are a common feature of PDE not explained by treatment lag. Future work utilizing tract-based approaches to understand inter- and intra-hemispheric connectivity patterns will help in the better understanding the structural aspects of this disease.
Authors: L A Tseng; L Teela; M C Janssen; L A Bok; M A A P Willemsen; R F Neuteboom; L Haverman; S M Gospe; C R Coughlin; C D M van Karnebeek Journal: Mol Genet Metab Rep Date: 2022-03-04
Authors: Udo Fh Engelke; Rianne E van Outersterp; Jona Merx; Fred Amg van Geenen; Arno van Rooij; Giel Berden; Marleen Cdg Huigen; Leo Aj Kluijtmans; Tessa Ma Peters; Hilal H Al-Shekaili; Blair R Leavitt; Erik de Vrieze; Sanne Broekman; Erwin van Wijk; Laura A Tseng; Purva Kulkarni; Floris Pjt Rutjes; Jasmin Mecinović; Eduard A Struys; Laura A Jansen; Sidney M Gospe; Saadet Mercimek-Andrews; Keith Hyland; Michèl Aap Willemsen; Levinus A Bok; Clara Dm van Karnebeek; Ron A Wevers; Thomas J Boltje; Jos Oomens; Jonathan Martens; Karlien Lm Coene Journal: J Clin Invest Date: 2021-08-02 Impact factor: 14.808