Andraz Smon1, Barbka Repic Lampret1, Urh Groselj1, Mojca Zerjav Tansek1, Jernej Kovac1, Dasa Perko1, Sara Bertok1, Tadej Battelino2, Katarina Trebusak Podkrajsek3. 1. University Medical Centre Ljubljana, University Children's Hospital, Bohoriceva 20, Ljubljana, Slovenia. 2. University Medical Centre Ljubljana, University Children's Hospital, Bohoriceva 20, Ljubljana, Slovenia; University of Ljubljana, Faculty of Medicine, Korytkova ulica 2, Ljubljana, Slovenia. 3. University Medical Centre Ljubljana, University Children's Hospital, Bohoriceva 20, Ljubljana, Slovenia; University of Ljubljana, Faculty of Medicine, Korytkova ulica 2, Ljubljana, Slovenia. Electronic address: katarina.trebusak@kclj.si.
Abstract
OBJECTIVES: Contrary to many western European countries, most south-eastern European countries do not have an expanded newborn screening (NBS) program using tandem mass spectrometry. This study would represent one of the first expanded NBS studies in south-eastern Europe and will enable the estimation of the incidences of IEM in Slovenia. We proposed an expanded NBS approach including next-generation sequencing (NGS) as a confirmational analysis. DESIGN & METHODS: We conducted a pilot study of expanded NBS for selected inborn errors of metabolism (IEM) in Slovenia including 10,048 NBS cards. We used an approach including tandem mass spectrometry followed by second tier tests including NGS. Based on the NBS results, 85 children were evaluated at a metabolic follow-up; 80 of them were analyzed using NGS. RESULTS: Altogether, glutaric acidemia type 1 was confirmed in one patient who was a compound heterozygote for two known causative GCDH variants. A patient with suspected very long-chain acyl-CoA dehydrogenase deficiency had negative metabolic follow-up tests, but had two heterozygous ACADVL variants; one known disease-causing variant and one indel, namely c.205-8_205-7delinsGC, that is predicted to be causative. Nine participants had elevated metabolites characteristic of 3-methylcrotonyl-CoA carboxylase deficiency, 2 of them had known causative homozygous variants in MCCC1. The other seven were heterozygous; two had a novel genetic variant c.149_151dupCCA (p.Thr50dup). Cumulative incidences of IEM in Slovenia were similar to other European countries. CONCLUSIONS: NGS proved to be valuable in explaining the abnormal metabolite concentrations in NBS as it enabled the differentiation between affected patients and mere heterozygotes, and it improved the turnaround time of genetic analysis. The results of this study will be instrumental in the routine implementation of expanded NBS in Slovenia.
OBJECTIVES: Contrary to many western European countries, most south-eastern European countries do not have an expanded newborn screening (NBS) program using tandem mass spectrometry. This study would represent one of the first expanded NBS studies in south-eastern Europe and will enable the estimation of the incidences of IEM in Slovenia. We proposed an expanded NBS approach including next-generation sequencing (NGS) as a confirmational analysis. DESIGN & METHODS: We conducted a pilot study of expanded NBS for selected inborn errors of metabolism (IEM) in Slovenia including 10,048 NBS cards. We used an approach including tandem mass spectrometry followed by second tier tests including NGS. Based on the NBS results, 85 children were evaluated at a metabolic follow-up; 80 of them were analyzed using NGS. RESULTS: Altogether, glutaric acidemia type 1 was confirmed in one patient who was a compound heterozygote for two known causative GCDH variants. A patient with suspected very long-chain acyl-CoA dehydrogenase deficiency had negative metabolic follow-up tests, but had two heterozygous ACADVL variants; one known disease-causing variant and one indel, namely c.205-8_205-7delinsGC, that is predicted to be causative. Nine participants had elevated metabolites characteristic of 3-methylcrotonyl-CoA carboxylase deficiency, 2 of them had known causative homozygous variants in MCCC1. The other seven were heterozygous; two had a novel genetic variant c.149_151dupCCA (p.Thr50dup). Cumulative incidences of IEM in Slovenia were similar to other European countries. CONCLUSIONS: NGS proved to be valuable in explaining the abnormal metabolite concentrations in NBS as it enabled the differentiation between affected patients and mere heterozygotes, and it improved the turnaround time of genetic analysis. The results of this study will be instrumental in the routine implementation of expanded NBS in Slovenia.
Authors: Nasser A Elhawary; Imad A AlJahdali; Iman S Abumansour; Ezzeldin N Elhawary; Nagwa Gaboon; Mohammed Dandini; Abdulelah Madkhali; Wafaa Alosaimi; Abdulmajeed Alzahrani; Fawzia Aljohani; Ehab M Melibary; Osama A Kensara Journal: Hum Genomics Date: 2022-07-19 Impact factor: 6.481
Authors: Janne Strand; Kiran Aftab Gul; Hans Christian Erichsen; Emma Lundman; Mona C Berge; Anette K Trømborg; Linda K Sørgjerd; Mari Ytre-Arne; Silje Hogner; Ruth Halsne; Hege Junita Gaup; Liv T Osnes; Grete A B Kro; Hanne S Sorte; Lars Mørkrid; Alexander D Rowe; Trine Tangeraas; Jens V Jørgensen; Charlotte Alme; Trude E H Bjørndalen; Arild E Rønnestad; Astri M Lang; Terje Rootwelt; Jochen Buechner; Torstein Øverland; Tore G Abrahamsen; Rolf D Pettersen; Asbjørg Stray-Pedersen Journal: Front Immunol Date: 2020-07-09 Impact factor: 7.561