Elevated Homocysteine after Elevated Propionylcarnitine or Low Methionine in Newborn Screening Is Highly Predictive for Low Vitamin B12 and Holo-Transcobalamin Levels in Newborns

Diagnostics

Bernadette Goeschl¹  Tomaž Rozmarič¹  Susanne Greber-Platzer¹  Maximilian Zeyda¹  Vassiliki Konstantopoulou¹  Goran Mitulović²  Martina Huemer³  Sabine Scholl-Bürgi⁴  Daniela Karall⁴  Barbara Plecko⁵  Johannes Spenger⁶  SaskiaB. Wortmann⁶ 

[1] Austrian Newborn Screening, Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria;Clinical Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria;Department of Paediatrics, Landeskrankenhaus Bregenz, 6900 Bregenz, Austria;Department of Pediatrics I (Inherited Metabolic Disorders), Medical University of Innsbruck, 6020 Innsbruck, Austria;Department of Pediatrics and Adolescent Medicine, Division of General Pediatrics, University Childrens’ Hospital Graz, Medical University Graz, 8036 Graz, Austria;University Children’s Hospital, Paracelsus Medical University, 5020 Salzburg, Austria;

关键词: vitamin B12;    newborn screening;    homocysteine;    methylmalonic acid;    dried blood spots;   

DOI  :  10.3390/diagnostics10090626

来源: DOAJ

【 摘 要 】

Early diagnostics and treatment of vitamin B12 deficiency (B12D) in infants, mainly maternally conditioned, is crucial in preventing possible developmental delay and neurological deficits. Currently, B12D is rarely listed in regular newborn screening panels and mostly regarded as an incidental finding. The aim of this study was to evaluate a targeted newborn screening strategy for detection of suspected B12D. A decision strategy based on the primary parameters propionylcarnitine and methionine for selection of samples to be analyzed for total homocysteine by mass spectrometry was established. Therefore, 93,116 newborns were initially screened. Concentrations of vitamin B12 and holotranscobalamin in serum were obtained from clinical follow-up analyses of recalled newborns. Moreover, an extremely sensitive mass spectrometric method to quantify methylmalonic acid from the dried blood spots was developed. Overall, 0.15% of newborns were screened positive for suspected B12D, of which 64% had vitamin B12 concentrations below 148 pM. We also determined a cutoff value for methylmalonic acid in dried blood spots indicative for B12D in infants. Overall, we calculated a prevalence of 92/100,000 for suspected B12D in the Austrian newborns. In conclusion, we present a screening algorithm including second-tier measurement of total homocysteine that allows detection of low B12 serum concentrations with a high detection rate and low false-positive rate.

【 授权许可】

Unknown