Lysine restricted diet for pyridoxine-dependent epilepsy: First evidence and future trials

Abstract

This observational study provides Level 4 evidence that lysine restriction is well tolerated with significant decrease of potentially neurotoxic biomarkers in different body compartments, and with the potential to improve developmental outcomes in children with PDE caused by ATQ deficiency. To generate a strong level of evidence before this potentially burdensome dietary therapy becomes the mainstay treatment, we have established: an international PDE consortium to conduct future studies with an all-inclusive integrated study design; a website containing up-to-date information on PDE; a methodological toolbox; and an online registry to facilitate the participation of interested physicians, scientists, and families in PDE research.

Lysine-Restricted Diet as Adjunct Therapy for Pyridoxine-Dependent Epilepsy: The PDE Consortium Consensus Recommendations

“…In analogy to other disorders of amino acid degradation (specifically GA-I), adjuvant treatment of ATQ deficiency with a lysine-restricted diet had been offered to some patients showing neurodevelopmental deficits in Vancouver (Canada), Hannover (Germany), and Denver (Colorado, US), as part of an observational study, with promising results (van Karnebeek et al 2012). Consequently, the Consortium undertook a systematic review of a lysinerestricted diet in PDE as a basis for recommendations on its application and a proposal for future studies.…”

“…PA accumulates due to backpressure from the enzymatic block of the recommendations. During these workshops it was agreed that, based on first and only evidence (van Karnebeek et al 2012), neonates and children with PDE due to ATQ deficiency may be offered a lysine-restricted diet as part of "improved clinical care." The importance of systematic outcome monitoring was also acknowledged and options for further studies to generate more evidence were discussed.…”

“…A second search using "pyridoxine dependent epilepsy" combined with "treatment" yielded an additional 12 publications (seven case series, two case reports, one biochemical methodological study, two reviews), but no controlled trials. To date, the only evidence (level IV) for this diet in PDE is that of Van Karnebeek et al (2012). This evidence, together with the updated guidelines for management of GA-1 and clinical expertise, provided the basis for the following recommendations.…”

“…The first dietary intervention for PDE was reported in an open-label, observational study that evaluated the effectiveness and safety of concomitant dietary lysine restriction and pyridoxine therapy using chemical biomarkers, seizure control, and developmental/cognitive outcomes in seven children with ATQ deficiency (van Karnebeek et al 2012). The results show that dietary lysine restriction (evidence level IV) in these children: (1) is tolerated without short-term adverse effects; (2) leads to decrease of potentially neurotoxic biomarkers in different body compartments; and (3) has potential benefit for seizure control and neurodevelopmental outcome.…”

Long-Term Follow-up of a Successfully Treated Case of Congenital Pyridoxine-Dependent Epilepsy

“…It seems likely that preservation of intellect is dependent upon adequate pyridoxine replacement (Baxter et al 1996), but may vary with differing genotypes (Striano et al 2009;Scharer et al 2010) or unknown environmental influences (Alfadhel et al 2012). Further restoration of higher functions may prove possible with additional dietary modification such as lysine restriction (van Karnebeek et al 2012), emphasizing the complex pathogenesis of antiquitin defects beyond that of central pyridoxine deficiency.…”