RT Journal Article
T1 Newborn screening for homocystinurias: Recent recommendations versus current practice.
A1 Keller, Rebecca
A1 Chrastina, Petr
A1 Pavlíková, Markéta
A1 Gouveia, Sofía
A1 Ribes, Antonia
A1 Kölker, Stefan
A1 Blom, Henk J
A1 Baumgartner, Matthias R
A1 Bártl, Josef
A1 Dionisi-Vici, Carlo
A1 Gleich, Florian
A1 Morris, Andrew A
A1 Kožich, Viktor
A1 Huemer, Martina
A1 individual contributors of the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD), 
A1 Barić, Ivo
A1 Ben-Omran, Tawfeq
A1 Blasco-Alonso, Javier
A1 Bueno Delgado, Maria A
A1 Carducci, Claudia
A1 Cassanello, Michela
A1 Cerone, Roberto
A1 Couce, Maria Luz
A1 Crushell, Ellen
A1 Delgado Pecellin, Carmen
A1 Dulin, Elena
A1 Espada, Mercedes
A1 Ferino, Giulio
A1 Fingerhut, Ralph
A1 Garcia Jimenez, Immaculada
A1 Gonzalez Gallego, Immaculada
A1 González-Irazabal, Yolanda
A1 Gramer, Gwendolyn
A1 Juan Fita, Maria Jesus
A1 Karg, Eszter
A1 Klein, Jeanette
A1 Konstantopoulou, Vassiliki
A1 la Marca, Giancarlo
A1 Leão Teles, Elisa
A1 Leuzzi, Vincenzo
A1 Lilliu, Franco
A1 Lopez, Rosa Maria
A1 Lund, Allan M
A1 Mayne, Philip
A1 Meavilla, Silvia
A1 Moat, Stuart J
A1 Okun, Jürgen G
A1 Pasquini, Elisabeta
A1 Pedron-Giner, Consuélo Carmen
A1 Racz, Gabor Zoltan
A1 Ruiz Gomez, Maria Angeles
A1 Vilarinho, Laura
A1 Yahyaoui, Raquel
A1 Zerjav Tansek, Moja
A1 Zetterström, Rolf H
A1 Zeyda, Maximilian
AB To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and decision limits were converted to multiples of the median (MoM) to allow comparison between centres. NBS programmes, algorithms and decision limits varied considerably. Only nine centres used the recommended second-tier marker total homocysteine (tHcy). The median decision limits of all centres were ≥ 2.35 for high and ≤ 0.44 MoM for low methionine, ≥ 1.95 for high and ≤ 0.47 MoM for low methionine/phenylalanine, ≥ 2.54 for high propionylcarnitine and ≥ 2.78 MoM for propionylcarnitine/acetylcarnitine. These decision limits alone had a 100%, 100%, 86% and 84% sensitivity for the detection of CBSD, MATI/IIID, iRMD and cRMD, respectively, but failed to detect six individuals with cRMD. To enhance sensitivity and decrease second-tier testing costs, we further adapted these decision limits using the data of 15 000 healthy newborns. Due to the favorable outcome of early treated patients, NBS for homocystinurias is recommended. To improve NBS, decision limits should be revised considering the population median. Relevant markers should be combined; use of the postanalytical tools offered by the CLIR project (Collaborative Laboratory Integrated Reports, which considers, for example, birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.
YR 2019
FD 2019
LK http://hdl.handle.net/10668/13541
UL http://hdl.handle.net/10668/13541
LA en
DS RISalud
RD Apr 12, 2025