Evaluation of implementation scenarios for national neonatalscreening of GAMT deficieny
Projectomschrijving
Uitbreiding neonatale hielprikscreening: onderzoek naar GAMT deficiëntie screening
Vraagstuk
Stofwisselingsziekten hebben grote gevolgen voor het kind en de familie. Voor sommige van deze ziekten is bij vroege opsporing middels de hielprikscreening tijdige behandeling mogelijk, waardoor het risico om met (ernstige) ziekteklachten op te groeien aanzienlijk wordt verkleind. Dit geldt ook voor guanidinoacetate methyltransferase deficiëntie (GAMT-D), een erfelijke stofwisselingsziekte met ontwikkelingsachterstand tot gevolg. Screening op deze ziekte is nog niet beschikbaar.
Onderzoek
Er is een meetmethode ontwikkeld waarmee de ziekte GAMT-D kan worden aangetoond. Er is tevens voor verschillende screenings-scenario’s onderzocht wat de logistieke, juridische, financiële, en psychosociale aspecten zijn als GAMT-D aan de nu bestaande hielprikscreening wordt toegevoegd. Ook zijn de perspectieven van ouders en zorgverleners onderzocht.
Uitkomst
Met de ontwikkelde methode en het meest optimale scenario lijkt implementatie in Nederland mogelijk. Dit is juridisch en ethisch verantwoord en biedt de meest robuuste en kostenbesparende methode om het leven van GAMT-D-patiënten te verbeteren. Vanuit het perspectief van de ouders en zorgverleners is GAMT-D vergelijkbaar met veel andere gescreende aangeboren stofwisselingsziekten en deze studie bracht geen psychosociale problemen van toevoeging van GAMT-D screening aan het licht.
Verslagen
Samenvatting van de aanvraag
In 2015 the Dutch Minister of Health took on the advice from the Health Council of the Netherlands to expand the national neonatal bloodspot screening (NBS) program with fourteen conditions. At that time, NBS included seventeen rare, congenital disorders where early treatment prevents or minimizes irreversible damage for the child. One of the conditions included in the expansion is guanidinoacetate methyltransferase deficiency (GAMT-D) (MIM#612736). GAMT-D is an autosomal recessive disorder of creatine biosynthesis causing developmental delay / intellectual disability in untreated patients as a result of irreversible brain damage occurring prior to diagnosis. In the Netherlands, the prevalence has been estimated to be 1:250,000 [1]. Treatment consists of high doses creatine to replenish cerebral creatine deficiency, ornithine supplementation and an arginine restricted diet. Normal neurodevelopmental outcome has been reported only in patients treated from the neonatal period, highlighting the importance of early treatment. Hence, the Dutch Minister of Health has decided on adding GAMT-D to NBS. The NBS program includes four regional laboratories and one reference laboratory throughout the Netherlands. Each laboratory tests bloodspot samples using the same analyzers and the same (commercially available) assays. The results are fed into a central database. Most conditions in NBS are analyzed via an one-tier approach, only a few need second or third tier testing, also commercially available. A commercial test kit for GAMT-D however is not available which means that an in-house test method needs to be evaluated and validated before including GAMT-D in NBS program. The proposed in-house test consists of three tier testing. Furthermore, several questions need to be addressed before adequate implementation of GAMT-D screening. To implement GAMT-D screening several scenarios are possible (Figure 1). 1) The current laboratory logistics will be sustained as much as possible by finding a commercial party that provides a test kit used by each laboratory for the first tier. 2) The in-house GAMT-D test will be tested and validated by three scenarios; a) all tiers included in the in-house test will be performed at one central laboratory; b) the first tier will be performed regionally, and the second and third tier will be performed at one central laboratory, or c) only the third tier will be performed centrally. Each scenario has different implications on elements that play an important role in the decision for adequate implementation of GAMT-D, such as costs, qualified personnel, logistics, and quality assurance. Therefore, the goal of the present study is to provide insight in the different potential scenarios, an evaluation of the relevant factors to decide on the best scenario, and an analysis of the algorithm that will give the highest quality test. Based on this evaluation, a balanced advice will be provided on how to implement GAMT-D in Dutch NBS.