Year of grant:
2017

Research Area:
Heilsa - Sjúkrakassagrunnurin

Project type:
Verkætlan

Project title:
Preventing cardiac disease through improved neonatal screening

Grant number:
3024

Project manager:
Katrin Eivindsdóttir Danielsen

Institution/company:
Landssjúkrahúsið/Ílegusavnið

Other participants:
Ulrike Steuerwald, Ron A. Wevers, Dr.Marcel Nelen

Project period:
Planned: 01.04.2019 – 31.03.2023
Actual: 01.04.2019 – 31.07.2023

Total budget:
1.728.981

Grant from the FRC in DKK:
953.715

Project description:
Original
The aims of this project are two: To initiate mutational analysis based neonatal screening for primary carnitine deficiency (PCD) and Glycogen storage disease IIIa (GSDIIIa) that have a high incidence in the Faroe Islands and can lead to severe cardiac disease when left untreated. The second aim is to set up the Molecular Inversion Probe (MIP) technique in the Faroe Islands that offers cost-effective mutational analysis and broadens the range of molecular laboratory techniques available.

Neonatal screening in the Faroe Islands follows the routine screening programme for Denmark at present. There are, however, concerns regarding the appropriateness of the programme. Firstly, the very high incidence of some disorders such as primary carnitine deficiency (PCD) in association with the estimated high rate of false negative results by routine tandem mass spectrometry analysis offers concerns. Secondly, glycogen storage disease type IIIa (GSD IIIa) has been shown to have a high incidence in the Faroe Islands but is not part of the neonatal screening programme although it fulfils all of the WHO criteria for inclusion of disorders in neonatal screening programs. Missed diagnosis for PCD and GSDIIIa can lead to significant morbidity involving the heart, and for PCD, sudden death in apparently healthy children and young adults. The mutations known to cause disease for PCD and GSDIIIa in Faroese individuals have been identified. In order to identify children with false negative results for PCD, and identify children with GSDIIIa, mutation analysis (MIP) will be performed for all new-borns in a trial period of three years to supplement routine neonatal screening. In addition to improving prognosis for children with these treatable disorders, it will provide valuable data on the rate of false negatives for CTD by mass spectrometry.

Final
The Faroe Islands are a genetically isolated population descending in large from a small number of settlers. As a result, a large number of founder mutations have been identified. The causative mutations for several disorders have been found to be the same in all affected Faroese individuals.

Three common treatable disorders in the Faroe Islands are part of the current neonatal screening programme. These are primary carnitine deficiency (PCD), holocarboxylase synthetase (HLCS) deficiency, and cystic fibrosis (CF). Another disorder with high incidence in the Faroe Islands is glycogen storage disease type IIIa (GSDIIIa). GSDIIIa is not part of the neonatal screening programme and there is no metabolic test available for detection of the disorder. Children with GSDIIIa are therefore diagnosed when clinically symptomatic.

The current tests for PCD and HLCS carry the risk of false negatives as they are based on measurements of metabolites at a time when maternal metabolites are still present in the newborn. Neonatal screening for CF has also been shown to produce false negative results. Furthermore, GSDIIIa is not part of the current neonatal screening programme. We therefore set out to perform targeted newborn sequencing as an additional test in newborn screening.

Almost 1600 blood samples were collected over three years, and analysis is still ongoing. Results will be published once they are ready.

Storage and access rights to collected data:
Data is stored on the server of the National Health Authority within Landsnet. Collected data belong to the National Health Authority and the only person outside the National Health Authority that can gain access to the data is the clinician in charge.

Project status:
Liðug

Project output:
Scientific articles, books, thesis etc.

Other results, such as unpublished articles, patents, computer systems, original models and new procedures

Manuscript in preparation

Publications outside the scientific community, i.e. lectures, periodicals, articles in newspapers, television and radio

- KVF - Dagur og vika og morgunsendingin 2019
- Vísindavøka 2019, 2020 og 2023
- Heilsugranskingardagur 2021
- CTD aðalfund 2019
- Arvasjúkan aðalfund 2023
- Framløga fyri ljósmøðrum 2019, barnalæknum 2023 og Heilsumálaráðnum í 2023.



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