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. 2017:32:87-94.
doi: 10.1007/8904_2016_556. Epub 2016 Jun 21.

Newborn Screening for Vitamin B6 Non-responsive Classical Homocystinuria: Systematical Evaluation of a Two-Tier Strategy

Jürgen G Okun  1 , Hongying Gan-Schreier  2 , Tawfeq Ben-Omran  3 , Kathrin V Schmidt  2 , Junmin Fang-Hoffmann  2 , Gwendolyn Gramer  2 , Ghassan Abdoh  3 , Noora Shahbeck  3 , Hilal Al Rifai  3 , Abdul Latif Al Khal  3 , Gisela Haege  2 , Chuan-Chi Chiang  4 , David C Kasper  5 , Bridget Wilcken  6 , Peter Burgard  2 , Georg F Hoffmann  2
Affiliations

Newborn Screening for Vitamin B6 Non-responsive Classical Homocystinuria: Systematical Evaluation of a Two-Tier Strategy

Jürgen G Okun et al. JIMD Rep. 2017.

Abstract

Background: In classical homocystinuria (HCU, MIM# 236200) due to the deficiency of cystathionine β-synthase (EC 4.2.1.22) there is a clear evidence for the success of early treatment. The aim of this study was to develop and evaluate a two-tier strategy for HCU newborn screening.

Methods: We reevaluated data from our newborn screening programme for Qatar in a total number of 125,047 neonates including 30 confirmed HCU patients. Our hitherto existing screening strategy includes homocysteine (Hcy) measurements in every child, resulting in a unique dataset for evaluation of two-tier strategies. Reevaluation included methionine (Met) levels, Met to phenylalanine (Phe) ratio, and Hcy. Four HCU cases identified after database closure were also included in the evaluation. In addition, dried blood spot samples selected by Met values >P97 in the newborn screening programs in Austria, Australia, the Netherlands, and Taiwan were analyzed for Hcy.

Results: Met to Phe ratio was found to be more effective for first sieve than Met, sorting out nearly 90% of normal samples. Only 10% of the samples would have to be processed by second-tier measurement of Hcy in dried blood spots. As no patient with HCU was found neither in the samples investigated for HCU, nor by clinical diagnosis in the other countries, the generalization of our two-tier strategy could only be tested indirectly.

Conclusion: The finally derived two-tier algorithm using Met to Phe ratio as first- and Hcy as second-tier requires 10% first-tier positives to be transferred to Hcy measurement, resulting in 100% sensitivity and specificity in HCU newborn screening.

Keywords: Classical homocystinuria; Cystathionine β-synthase; Dried blood spots; Homocysteine; Newborn screening; Two-tier strategy.

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Figures

Fig. 1
Fig. 1
Met/Phe and Hcy for upper three percent of Met distribution of all samples and for Qatar homocystinuria patients; red stars indicate cases with confirmed HCU found after data analysis
See this image and copyright information in PMC

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