Neuropediatrics 2013; 44 - FV12_04
DOI: 10.1055/s-0033-1337718

Lysine restricted diet for pyridoxine-dependent epilepsy: First reports and future trial

C van Karnebeek 1, H Hartmann 2, S Jaggumantri 1, L Bok 3, A Das 2 S Gospe 4Jr., C Jakobs 5, U Meyer 2, J Van Hove 6, E Struys 5, S Stöckler 1, B Plecko 7
  • 1Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada
  • 2Medizinische Hochschule Hannover, Zentrum Kinderheilkunde und Jugendmedizin, Hannover, Germany
  • 3Department of Pediatrics, Maxima Medical Center, Veldhoven, The Netherlands
  • 4Department of Neurology, University of Washington and Seattle Children's Hospital, Seattle WA, United States
  • 5Metabolic Unit, Department of Clinical Chemistry, VU Medical Center Amsterdam, Amsterdam, The Netherlands
  • 6Department of Pediatrics, University of Colorado, Aurora, United States
  • 7Neuropädiatrie, Universitätskinderkliniken Zürich, Zürich, Switzerland

Aims: To evaluate the efficacy and safety of dietary lysine restriction as an adjunct to pyridoxine therapy on biochemical parameters, seizure control, and developmental/cognitive outcomes in children with pyridoxine-dependent epilepsy (PDE) caused by antiquitin (ATQ) deficiency.

Methods: Seven children aged from 28 days to 11.9 years with confirmed ATQ deficiency were treated with a dietary lysine restriction over a period of 4 months to 4.9 years. Biochemical outcomes were evaluated using pipecolic acid and α-aminoadipic semialdehyde (AASA) levels in body fluids. Developmental/cognitive outcomes were evaluated using age-appropriate tests and parental observations.

Results: Lysine restriction was well tolerated with good compliance. No adverse events were reported. Reduction in biomarker levels (baseline values before and first values after initiation of dietary lysine restriction) ranged from 20 to 67% for plasma pipecolic acid, 13 to 72% for urinary AASA, and 45% for plasma AASA. In one patient, decrease of cerebrospinal fluid levels of PA of 87% and of AASA of 82% was demonstrated. Improvement in age-appropriate skills was reported/observed in four of five patients showing prediet delays.

Conclusion: This first observational study provides level 4 evidence that lysine restriction is well tolerated. Significant reduction of potentially neurotoxic biomarkers was measured in different body compartments, with the potential to improve developmental outcomes in children with PDE caused by ATQ deficiency. Preliminary results have recently been published.1 The potentially burdensome dietary treatment cannot yet be recommended as mainstay therapy. In 2013, a prospective, international multicenter-controlled trial will be launched to further investigate the effect of the diet and achieve a higher level of evidence.

Reference

1. van Karnebeek CD, et al. Lysine restricted diet for pyridoxine-dependent epilepsy: First evidence and future trials 2012;107(3):335 – 344