PDE due to antiquitin (ATQ) deficiency: altered lysine metabolism

Deficiency of lysine degradation can lead to the chemical inactivation of pyridoxine, leading to potentially damaging levels of neurotoxic substances.

Adjunct Lysine Reduction Therapies (LRT): Lysine Restricted Diet & Arginine Supplementation

Pyridoxine treatment is symptomatic for seizures as it helps overcome the Vitamin B6 deficiency due chemical inactivation by accumulating substances such as P6C. Lysine restriction and arginine supplementation may be causal therapy as they reduce this accumulation and potentially prevent or minimize neurotoxicity leading to cognitive and developmental deficits. Observational studies show reductions in neurotoxic metabolites (urine AASA, plasma PA) along with improved seizure control as well as indications of behavioral and neurodevelopmental progress in several but not all patients. Combination of lysine restricted diet and arginine shows even further reductions. Early initiation of LRT seems most beneficial for outcome.

Consensus guidelines 2020

Consensus guidelines for the diagnosis and management of patients with PDE due to ATQ deficiency are established including 29 recommendations.

PDE registry

As is the case with all Rare Disease research, the answer lies in the numbers. We need tools and strategies to get more patients and committed health care professionals involved. Implementation of novel trial methodologies for small patient numbers is another key to success. The PDE Registry forms the basis; we need to map out our patients and colleagues interested in improving outcomes for this metabolic epilepsy.

Ultimate goal: PDE in Newborn screening

With the use of the PDE registry for natural history of PDE and treatment outcomes, we are working towards meeting the Wilson & Jungner criteria for implementation in newborn screening. Biomarkers suitable for newborn screening have been identified, such as 2-OPP.

Only by working together we can collect the required data to achieve our goals

Interested health care professionals have diverse PDE areas of expertise and within their own sphere of engagement, contacts with patients and families with PDE. Working together, we can increase and improve levels of evidence, understand which patients benefit the most, discern which features are amenable to treatment, and determine the short and long-term effects of therapy. This contact benefits all concerned.

Our PDE Research Framework utilizes an all-inclusive approach to unite patients, physicians and scientists around the world

  • international collaboration
  • joint research projects and funding applications
  • annual workshops & meetings
  • application of novel trial methodologies and designs
  • patient & family involvement

PDE is online

  • With the use of this website we provide up-to-date disease information and access to protocols
  • The online International PDE registry (>130 patients entered already), also serving as a basis for PDE research for all interested professionals
  • Leveraging social media for connecting all interested in the planning stages
  • Uniting patients across the globe and providing a platform for participatory research

The PDE Research Framework is poised to tackle the challenges and lead the way in rare disease research

Rare diseases come with their own sets of problems. Obscurity, lack of health-related commercial value, low patient numbers for the purposes of research and treatment investigation and small pool of interested clinicians and scientist. It is because of this, that we in the PDE Research Framework engage in innovative studies. Our studies involve the use of revised N-of-1 and cohort studies to obtain various evidence levels and meaningful outcome data.