Newborn Screening for Vitamin B12 Deficiency in Germany—Strategies, Results, and Public Health Implications

Can Newborn Screening for Vitamin B12 Deficiency be Incorporated into All Newborn Screening Programs?

“…Therapy with intramuscular B 12 led to rapid normalization of the hematologic and metabolic abnormalities and improvement in developmental progression, however, the infants usually had some degree of persistent neurologic impairment. [8][9][10] In this volume of The Journal, Gramer et al 11 demonstrate in a large study that a 2-tiered extension of newborn screening (NBS) leading to presymptomatic identification of vitamin B 12 deficiency is a facile and economical method to identify neonatal vitamin B 12 deficiency. The study employs 2 primary NBS markers with second tier testing of the NBS specimen: reduced methionine (and/or methionine/phenylalanine ratio) and increased C3 (and/or C3/C2 ratio) followed by second tier measurements of homocysteine and methylmalonic acid, respectively.…”

The Combined Impact of CLIR Post-Analytical Tools and Second Tier Testing on the Performance of Newborn Screening for Disorders of Propionate, Methionine, and Cobalamin Metabolism

“…After 15 years of clinical utilization, there is strong evidence that the biochemical 2TTs for disorders of propionate, methionine, and cobalamin metabolism have contributed to performance improvement of newborn screening by MS/MS, a reality validated by its replication worldwide with a combination of modifications and enhancements [27][28][29][30][31][32]. Like in the case of succinylacetone [10], it is now possible to analyze tHcy as part of the first tier screening when warranted by a high local incidence of Homocystinuria [33].…”

Primary carnitine deficiency – diagnosis after heart transplantation: better late than never!

“…In addition to newborn screening in line with the German newborn screening panel, this child participated in the pilot study "Newborn Screening 2020" at the newborn screening centre in Heidelberg, Germany. Since 2016, this study has been evaluating the possible extension of the German newborn screening panel by 26 additional conditions including PCD [7]. Newborn screening via tandem mass spectrometry in this study's protocol revealed severely reduced levels of free carnitine.…”

“…However, as the respective marker free carnitine (C0) is required when screening for other conditions in the German newborn screening panel, markedly decreased C0 levels are reported by newborn screening laboratories as incidental findings. Pilot studies are now evaluating an extension of the newborn screening panel to include PCD also in individual screening laboratories in Germany [6,7]. However, the New Zealand newborn screening programme just recently decided to discontinue screening for PCD; their reasons included poor sensitivity, a high false-positive rate, and numerous asymptomatic adults with PCD [8].…”