Target Diseases for Neonatal Screening in Germany

Abstract

Background: Neonatal screening in Germany currently comprises 19 congenital diseases, 13 of which are metabolic diseases. Approximately one in 1300 newborns suffers from one of these target diseases. Early diagnosis and treatment enable the affected children to undergo better development and even, in many cases, to have a normal life.

Methods: This review is based on pertinent publications retrieved by a selective search in the PubMed and Embase databases.

Results: Positive screening findings are confirmed in approximately one out of five newborns. The prompt evaluation of suspected diagnoses is essential, as treatment for some of these diseases must be initiated immediately after birth to prevent longterm sequelae. The most commonly identified diseases are primary hypothyroidism (1:3338), phenylketonuria/hyperphenylalaninemia (1 : 5262), cystic fibrosis (1 : 5400), and medium-chain acyl-CoA dehydrogenase deficiency (1 : 10 086). Patient numbers are rising as new variants of the target diseases are being identified, and treatments must be adapted to their heterogeneous manifestations. Precise diagnosis and the planning of treatment, which is generally lifelong, are best carried out in a specialized center.

Conclusion: Improved diagnosis and treatment now prolong the lives of many patients with congenital diseases. The provision of appropriate long-term treatment extending into adulthood will be a central structural task for screening medicine in the future.

Figure 1

Target diseases of neonatal screening in the USA 61 diseases have been target diseases for neonatal screening in the USA since July 2018. 35 of them are defined as core diseases, while the remaining 26 are secondary diseases that are automatically co-identified by the screening method used, tandem mass spectrometry (8). More than 80% (49/61) of the target diseases of the 61 target diseases are metabolic diseases. Three metabolic diseases that are targets of the German neonatal screening program are secondary diseases in the United States. The remaining 15 target diseases of the German program are core diseases in the USA.

Figure 2

a) Neonatal screening as a component of a complex diagnostic and therapeutic process The course of action after positive neonatal screening (NBS) is shown. Patients may remain asymptomatic or develop symptoms at various times, including in adulthood, and the phenotypes are variable. This is true both for the target diseases of neonatal screening and for other congenital metabolic diseases that are not targeted. In view of the heterogeneity of phenotypes, treatments must be periodically reevaluated and adjusted. b) Timeline of the development of neonatal screening in Germany The diagram shows the development of newborn screening since 1969 and predicted case numbers in the future. By the year 2050, it is expected that screening will have identified 26 000 patients with the defined target diseases (1).