Gwendolyn Gramer1, Junmin Fang-Hoffmann2, Patrik Feyh2, Glynis Klinke2, Peter Monostori2, Ulrike Mütze2, Roland Posset2, Karl Heinz Weiss3, Georg F Hoffmann2, Jürgen G Okun2. 1. Division of Neuropaediatrics and Metabolic Medicine, Centre for Paediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: gwendolyn.gramer@med.uni-heidelberg.de. 2. Division of Neuropaediatrics and Metabolic Medicine, Centre for Paediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany. 3. Department of Internal Medicine IV, Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg, Germany.
Abstract
OBJECTIVE: To evaluate a systematic newborn screening (NBS) strategy for vitamin B12 deficiency. STUDY DESIGN: In a prospective single-center NBS study, a systematic screening strategy for vitamin B12 deficiency was developed and evaluated. Tandem-mass spectrometry screening was complemented by 2 second-tier strategies, measuring methylmalonic/3-OH-propionic/methylcitric acid, and homocysteine from dried blood spots. RESULTS: In a cohort of 176 702 children screened over 27 months, 33 children were detected by NBS in whom (maternal) vitamin B12 deficiency was confirmed. Homocysteine was the most sensitive marker for vitamin B12 deficiency, but only combination with a second-tier strategy evaluating methylmalonic acid allowed for detection of all 33 children. Mothers were of various ethnic origins, and 89% adhered to a balanced diet. Treatment in children was performed predominantly by oral vitamin B12 supplementation (84%), and all children remained without clinical symptoms at short-term follow-up. CONCLUSIONS: Vitamin B12 deficiency is a treatable condition but can cause severe neurologic sequelae in infants if untreated. The proposed screening strategy is feasible and effective to identify moderate and severe cases of vitamin B12 deficiency. With an incidence of 1:5355 newborns, vitamin B12 deficiency is more frequent than inborn errors of metabolism included in NBS panels. Treatment of vitamin B12 deficiency is easy, and additional benefits can be achieved for previously undiagnosed affected mothers. This supports inclusion of vitamin B12 deficiency into NBS but also stresses the need for increased awareness of vitamin B12 deficiency in caregivers of pregnant women.
OBJECTIVE: To evaluate a systematic newborn screening (NBS) strategy for vitamin B12 deficiency. STUDY DESIGN: In a prospective single-center NBS study, a systematic screening strategy for vitamin B12 deficiency was developed and evaluated. Tandem-mass spectrometry screening was complemented by 2 second-tier strategies, measuring methylmalonic/3-OH-propionic/methylcitric acid, and homocysteine from dried blood spots. RESULTS: In a cohort of 176 702 children screened over 27 months, 33 children were detected by NBS in whom (maternal) vitamin B12 deficiency was confirmed. Homocysteine was the most sensitive marker for vitamin B12 deficiency, but only combination with a second-tier strategy evaluating methylmalonic acid allowed for detection of all 33 children. Mothers were of various ethnic origins, and 89% adhered to a balanced diet. Treatment in children was performed predominantly by oral vitamin B12 supplementation (84%), and all children remained without clinical symptoms at short-term follow-up. CONCLUSIONS:Vitamin B12 deficiency is a treatable condition but can cause severe neurologic sequelae in infants if untreated. The proposed screening strategy is feasible and effective to identify moderate and severe cases of vitamin B12 deficiency. With an incidence of 1:5355 newborns, vitamin B12 deficiency is more frequent than inborn errors of metabolism included in NBS panels. Treatment of vitamin B12 deficiency is easy, and additional benefits can be achieved for previously undiagnosed affected mothers. This supports inclusion of vitamin B12 deficiency into NBS but also stresses the need for increased awareness of vitamin B12 deficiency in caregivers of pregnant women.
Authors: Jaka Sikonja; Urh Groselj; Maurizio Scarpa; Giancarlo la Marca; David Cheillan; Stefan Kölker; Rolf H Zetterström; Viktor Kožich; Yann Le Cam; Gulcin Gumus; Valentina Bottarelli; Mirjam van der Burg; Eugenie Dekkers; Tadej Battelino; Johan Prevot; Peter C J I Schielen; James R Bonham Journal: Int J Neonatal Screen Date: 2022-05-06
Authors: Judit García-Villoria; Antonia Ribes; Sonia Pajares; Jose Antonio Arranz; Aida Ormazabal; Mireia Del Toro; Ángeles García-Cazorla; Aleix Navarro-Sastre; Rosa María López; Silvia María Meavilla; Mariela Mercedes de Los Santos; Camila García-Volpe; Jose Manuel González de Aledo-Castillo; Ana Argudo; Jose Luís Marín; Clara Carnicer; Rafael Artuch; Frederic Tort; Laura Gort; Rosa Fernández Journal: Orphanet J Rare Dis Date: 2021-04-30 Impact factor: 4.123