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 favourable 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, e.g. birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.

Newborn screening for homocystinurias: recent recommendations versus current practice / Keller, R.; Chrastina, P.; Pavlíková, M.; Gouveia, S.; Ribes, A.; Kölker, S.; Blom, H.J.; Baumgartner, M.R.; Bártl, J.; Dionisi Vici, C.; Gleich, F.; Morris, A.A.; Kožich, V.; Huemer, M.; Barić, I.; Ben-Omran, T.; Blasco-Alonso, J.; Bueno Delgado, M.A.; Carducci, C.; Cassanello, M.; Cerone, R.; Couce, M.L.; Crushell, E.; Delgado Pecellin, C.; Dulin, E.; Espada, M.; Ferino, G.; Fingerhut, R.; Garcia Jimenez, I.; Gonzalez Gallego, I.; González-Irazabal, Y.; Gramer, G.; Juan Fita, M.J.; Karg, E.; Klein, J.; Konstantopoulou, V.; la Marca, G.; Leão Teles, E.; Leuzzi, V.; Lilliu, F.; Lopez, R.M.; Lund, A.M.; Mayne, P.; Meavilla, S.; Moat, S.J.; Okun, J.G.; Pasquini, E.; Pedron-Giner, C.; Racz, G.Z.; Ruiz Gomez, M.A.; Vilarinho, L.; Yahyaoui, R.; Zerjav Tansek, M.; Zetterström, R.H.; Zeyda, M.. - In: JOURNAL OF INHERITED METABOLIC DISEASE. - ISSN 0141-8955. - ELETTRONICO. - (2019), pp. 128-139. [10.1002/jimd.12034]

Newborn screening for homocystinurias: recent recommendations versus current practice

la Marca, G.;PASQUINI, ELISABETTA;
2019

Abstract

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 favourable 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, e.g. birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.
2019
128
139
Goal 3: Good health and well-being for people
Keller, R.; Chrastina, P.; Pavlíková, M.; Gouveia, S.; Ribes, A.; Kölker, S.; Blom, H.J.; Baumgartner, M.R.; Bártl, J.; Dionisi Vici, C.; Gleich, F.; ...espandi
File in questo prodotto:
File Dimensione Formato  
Keller_Text_MH_submitted.pdf

accesso aperto

Tipologia: Preprint (Submitted version)
Licenza: Open Access
Dimensione 751.17 kB
Formato Adobe PDF
751.17 kB Adobe PDF
jimd.12034.pdf

Accesso chiuso

Tipologia: Pdf editoriale (Version of record)
Licenza: Tutti i diritti riservati
Dimensione 1.64 MB
Formato Adobe PDF
1.64 MB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1135402
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 37
  • ???jsp.display-item.citation.isi??? 34
social impact