Newborn screening by tandem mass spectrometry for glutaric aciduria type 1: a cost-effectiveness analysis

Abstract

BackgroundGlutaric aciduria type I (GA-I) is a rare metabolic disorder caused by inherited deficiency of glutaryl-CoA dehydrogenase. Despite high prognostic relevance of early diagnosis and start of metabolic treatment as well as an additional cost saving potential later in life, only a limited number of countries recommend newborn screening for GA-I. So far only limited data is available enabling health care decision makers to evaluate whether investing into GA-I screening represents value for money. The aim of our study was therefore to assess the cost-effectiveness of newborn screening for GA-I by tandem mass spectrometry (MS/MS) compared to a scenario where GA-I is not included in the MS/MS screening panel.MethodsWe assessed the cost-effectiveness of newborn screening for GA-I against the alternative of not including GA-I in MS/MS screening. A Markov model was developed simulating the clinical course of screened and unscreened newborns within different time horizons of 20 and 70 years. Monte Carlo simulation based probabilistic sensitivity analysis was used to determine the probability of GA-I screening representing a cost-effective therapeutic strategy.ResultsWithin a 20 year time horizon, GA-I screening averts approximately 3.7 DALYs (95% CI 2.9 – 4.5) and about one life year is gained (95% CI 0.7 – 1.4) per 100,000 neonates screened initially . Moreover, the screening programme saves a total of around 30,682 Euro (95% CI 14,343 to 49,176 Euro) per 100,000 screened neonates over a 20 year time horizon.ConclusionWithin the limitations of the present study, extending pre-existing MS/MS newborn screening programmes by GA-I represents a highly cost-effective diagnostic strategy when assessed under conditions comparable to the German health care system.

A case of glutaric aciduria type 1 diagnosed at an early age

“…Düzelmeyen distoni veya koreatetoz olgularında bu hastalığın taranması önerilmektedir. Erken tanı ve tedaviyle nörolojik hasarlanmanın önlenebil-mesi nedeniyle bazı ülkelerde tandem-mass spektrometre ile glutaril karnitin artışı tarama testi olarak kullanılmaktadır (4,7,11) . Ancak hastamızda, yenidoğan döneminde metabolik hastalıklara yönelik olarak tetkik edilmemişti.…”

“…Hastalığa neden olan gen 19p13.2'de tanımlanmış-tır (2,4) . Genellikle ilk üç yaşta hafif bir enfeksiyonu takiben başlayan akut bilinç bozukluğu tablosu ve kazanılmış motor becerilerin kaybıyla beraber, diskinetik veya distonik hareket bozuklukları görülür (1)(2)(3) .…”

“…Genellikle ilk üç yaşta hafif bir enfeksiyonu takiben başlayan akut bilinç bozukluğu tablosu ve kazanılmış motor becerilerin kaybıyla beraber, diskinetik veya distonik hareket bozuklukları görülür (1)(2)(3) . Hastalığa erken tanı konmasıyla tedavi altına alınan hastaların prognozunun iyi olduğu bildirilmektedir (4) . Bu makalede, alt solunum yolu enfeksiyonu nedeniyle başvuran, distonik hareketleri ve konvülziyonu gözlenen ve makrosefalisi saptanan altı aylık bir erkek hasta sunularak glutarik asidüri Tip 1'de erken tanı ve tedavinin öneminin vurgulanması amaçlanmıştır.…”

GAI – distinct genotype and phenotype characteristics in reported Slovak patients

“…From this point of view, the diagnostic approach based on NBS is benefi cial. The experience with NBS in other countries showed that the majority of newborns are asymptomatic though a macrocephaly and neurological symptoms such as hypotonia and asymmetric posturing are often present (23). Therefore, the NBS is even more important in a high-risk population such as: the Amish Community in Pennsylvania (USA), the original inhabitants of the Canadian province of Ontario and Manitoba called Oji-Cree (Canada), the Irish travellers (U.K.), the Lumbee tribe in North Carolina (USA) and the indigenous inhabitants of South Africa (17), where the prevalence of GAI should be up to 1: 300.…”

Newborn Screening Programmes in Europe, Arguments and Efforts Regarding Harmonisation: Focus on Organic Acidurias

“…NBS and subsequent treatment of GA-I according to an international guideline have significantly improved the neurological outcome of affected individuals (Heringer et al 2010;K€ olker et al 2006, 2007, and NBS is considered a cost-effective diagnostic strategy for countries with healthcare systems comparable to Germany (Pfeil et al 2013). According to this international guideline, it is crucial to start treatment early before the manifestation of irreversible neurologic damage (K€ olker et al 2011).…”