TY - JOUR
T1 - Evaluation of 11 years of newborn screening for maple syrup urine disease in the Netherlands and a systematic review of the literature
T2 - Strategies for optimization
AU - Stroek, Kevin
AU - Boelen, Anita
AU - Bouva, Marelle J.
AU - De Sain-van der Velden, Monique
AU - Schielen, Peter C.J.I.
AU - Maase, Rose
AU - Engel, Henk
AU - Jakobs, Bernadette
AU - Kluijtmans, Leo A.J.
AU - Mulder, Margot F.
AU - Rubio-Gozalbo, M. E.
AU - van Spronsen, Francjan J.
AU - Visser, Gepke
AU - de Vries, Maaike C.
AU - Williams, Monique
AU - Heijboer, Annemieke C.
AU - Kemper, Evelien A.
AU - Bosch, Annet M.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Maple syrup urine disease (MSUD) leads to severe neurological deterioration unless diagnosed early and treated immediately. We have evaluated the effectiveness of 11 years of MSUD newborn screening (NBS) in the Netherlands (screening >72 hours, referral if both total leucine (Xle) and valine ≥400 μmol/L blood) and have explored possibilities for improvement by combining our data with a systematic literature review and data from Collaborative Laboratory Integrated Reports (CLIR). Dutch MSUD NBS characteristics and accuracy were determined. The hypothetical referral numbers in the Dutch population of additional screening markers suggested by CLIR were calculated. In a systematic review, articles reporting NBS leucine concentrations of confirmed patients were included. Our data showed that NBS of 1 963 465 newborns identified 4 MSUD patients and led to 118 false-positive referrals (PPV 3.28%; incidence 1:491 000 newborns). In literature, leucine is the preferred NBS parameter. Total leucine (Xle) concentrations (mass-spectrometry) of 53 detected and 8 false-negative patients (sampling age within 25 hours in 3 patients) reported in literature ranged from 288 to 3376 (median 900) and 42 to 325 (median 209) μmol/L blood respectively. CLIR showed increasing Xle concentrations with sampling age and early NBS sampling and milder variant MSUD phenotypes with (nearly) normal biochemical profiles are causes of false-negative NBS results. We evaluated the effect of additional screening markers and established the Xle/phenylalanine ratio as a promising additional marker ratio for increasing the PPV, while maintaining high sensitivity in the Dutch MSUD NBS.
AB - Maple syrup urine disease (MSUD) leads to severe neurological deterioration unless diagnosed early and treated immediately. We have evaluated the effectiveness of 11 years of MSUD newborn screening (NBS) in the Netherlands (screening >72 hours, referral if both total leucine (Xle) and valine ≥400 μmol/L blood) and have explored possibilities for improvement by combining our data with a systematic literature review and data from Collaborative Laboratory Integrated Reports (CLIR). Dutch MSUD NBS characteristics and accuracy were determined. The hypothetical referral numbers in the Dutch population of additional screening markers suggested by CLIR were calculated. In a systematic review, articles reporting NBS leucine concentrations of confirmed patients were included. Our data showed that NBS of 1 963 465 newborns identified 4 MSUD patients and led to 118 false-positive referrals (PPV 3.28%; incidence 1:491 000 newborns). In literature, leucine is the preferred NBS parameter. Total leucine (Xle) concentrations (mass-spectrometry) of 53 detected and 8 false-negative patients (sampling age within 25 hours in 3 patients) reported in literature ranged from 288 to 3376 (median 900) and 42 to 325 (median 209) μmol/L blood respectively. CLIR showed increasing Xle concentrations with sampling age and early NBS sampling and milder variant MSUD phenotypes with (nearly) normal biochemical profiles are causes of false-negative NBS results. We evaluated the effect of additional screening markers and established the Xle/phenylalanine ratio as a promising additional marker ratio for increasing the PPV, while maintaining high sensitivity in the Dutch MSUD NBS.
KW - dried blood spots
KW - leucine
KW - maple syrup urine disease
KW - mass-spectrometry
KW - newborn screening
KW - positive predictive value
KW - valine
UR - http://www.scopus.com/inward/record.url?scp=85094930091&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/jmd2.12124
DO - https://doi.org/10.1002/jmd2.12124
M3 - Article
C2 - 32685353
SN - 2192-8304
VL - 54
SP - 68
EP - 78
JO - JIMD reports
JF - JIMD reports
IS - 1
ER -