TY - JOUR
T1 - Newborn screening for homocystinurias
T2 - Recent recommendations versus current practice
AU - and individual contributors of the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD)
AU - Keller, Rebecca
AU - Chrastina, Petr
AU - Pavlíková, Markéta
AU - Gouveia, Sofía
AU - Ribes, Antonia
AU - Kölker, Stefan
AU - Blom, Henk J
AU - Baumgartner, Matthias R
AU - Bártl, Josef
AU - Dionisi-Vici, Carlo
AU - Gleich, Florian
AU - Morris, Andrew A
AU - Kožich, Viktor
AU - Huemer, Martina
AU - Barić, Ivo
AU - Ben-Omran, Tawfeq
AU - Blasco-Alonso, Javier
AU - Bueno Delgado, Maria A
AU - Carducci, Claudia
AU - Cassanello, Michela
AU - Cerone, Roberto
AU - Couce, Maria Luz
AU - Crushell, Ellen
AU - Delgado Pecellin, Carmen
AU - Dulin, Elena
AU - Espada, Mercedes
AU - Ferino, Giulio
AU - Fingerhut, Ralph
AU - Garcia Jimenez, Immaculada
AU - Gonzalez Gallego, Immaculada
AU - González-Irazabal, Yolanda
AU - Gramer, Gwendolyn
AU - Juan Fita, Maria Jesus
AU - Karg, Eszter
AU - Klein, Jeanette
AU - Konstantopoulou, Vassiliki
AU - la Marca, Giancarlo
AU - Leão Teles, Elisa
AU - Leuzzi, Vincenzo
AU - Lilliu, Franco
AU - Lopez, Rosa Maria
AU - Lund, Allan M
AU - Mayne, Philip
AU - Meavilla, Silvia
AU - Moat, Stuart J
AU - Okun, Jürgen G
AU - Pasquini, Elisabeta
AU - Pedron-Giner, Consuélo Carmen
AU - Racz, Gabor Zoltan
AU - Ruiz Gomez, Maria Angeles
N1 - © 2018 SSIEM.
PY - 2019/1
Y1 - 2019/1
N2 - PURPOSE: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.
AB - PURPOSE: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.
U2 - 10.1002/jimd.12034
DO - 10.1002/jimd.12034
M3 - Article
C2 - 30740731
VL - 42
SP - 128
EP - 139
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
SN - 0141-8955
IS - 1
ER -