Newborn screening for remethylation disorders and vitamin B12 deficiency-evaluation of new strategies in cohorts from Qatar and Germany

• Published in: World journal of pediatrics : WJP 2017-04, Vol.13 (2), p.136-143
• Main Authors: Gramer, Gwendolyn, Abdoh, Ghassan, Ben-Omran, Tawfeg, Shahbeck, Noora, Ali, Rehab, Mahmoud, Laila, Fang-Hoffmann, Junmin, Hoffmann, Georg F., Al Rifai, Hilal, Okun, Jürgen G.
• Format: Article
• Language: English
• Subjects: Critical Care Medicine; Imaging; Intensive; Maternal and Child Health; Medicine; Medicine & Public Health; Original Article; Pediatric Surgery; Pediatrics; Radiology; Surgery
• ISSN: 1708-8569; 1867-0687
• DOI: 10.1007/s12519-017-0003-z

Background Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine- ß -synthase deficiency). Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from Qatar. Methods A new optimized newborn screening strategy for remethylation disorders and homocystinuria was developed and evaluated for newborns from Qatar using total homocysteine measurement as first-tier and methionine, methionine-phenylalanine-ratio and propionylcarnitine as second-tiers. Proposed cut-offs were also retrospectively evaluated in newborn screening samples of 12 patients with remethylation disorders and vitamin B 12 deficiency from Qatar and Germany. Results Over a 12 months period, the proposed strategy led to a decrease in the recall rate in homocysteine screening for Qatar from 1.09% to 0.68%, while allowing for additional systematic inclusion of remethylation disorders and vitamin B 12 deficiency into the screening panel for Qatar. In the evaluated period the applied strategy would have detected all patients with classical homocystinuria identified by the previous strategy and in addition 5 children with maternal nutritional vitamin B 12 deficiency and one patient with an isolated remethylation disorder. Additional retrospective evaluation of newborn screening samples of 12 patients from Germany and Qatar with remethlyation disorders or vitamin B 12 deficiency showed that all of these patients would have been detected by the cut-offs used in the proposed new strategy. In addition, an adapted strategy for Germany using methionine, methionine-phenylalanine-ratio and propionylcarnitine as first-tier, and homocysteine as a second-tier test was also positively evaluated retrospectively. Conclusions The proposed strategy for samples from Qatar allows inclusion of remethylation disorders and vitamin B 12 deficiency in the screening panel, while lowering the recall rate. An adapted second-tier strategy is presented for screening in Germany and will be prospectively evaluated over the next years in a pilot project named “Newborn Screening 2020”.