Vitamin B₁₂ Deficiency in Infancy: The Case for Screening

Abstract

The classic principles put forth by Wilson and Jungner are often applied to determine the suitability of a condition for universal newborn screening. The three cases described here portray the harmful effects of vitamin B12 deficiency in infancy. The challenges and opportunities of early recognition and treatment are highlighted. Screening newborns would allow early detection and prevention of severe neurological damage in vitamin B12 -deficient infants and enable diagnosis of unrecognized maternal pernicious anemia in asymptomatic mothers. However, lack of standardized methodology and screening cutoffs present challenges to the use of current tandem mass spectrometry technologies for screening.

Simultaneous determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in dried blood spots: Second-tier LC-MS/MS assay for newborn screening of propionic acidemia, methylmalonic acidemias and combined remethylation disorders

“…As concerns maternal vitamin B 12 deficiency, such patients are expected to be partially identified by the suggested second-tier strategy, as at least severe cases show elevation of C3 and MMA on NBS [ 35 , 36 ]. Moreover, a clear benefit of early detection and treatment for both the child and the mother in severe maternal vitamin B 12 deficiency has been reported [ 37 – 39 ]. Thus, in our opinion, the identification of these patients may be regarded as a further advantage of the proposed strategy, in spite of a reported increase in false-positive rates [ 35 – 39 ].…”

Acquired Vitamin B12 Deficiency in Infancy

“…This is possible through measuring propionyl carnitine (C3) as a surrogate marker of cobalamin deficiency. [36][37][38][39] Yield from this is variable, reported from 0.88/100,000 37 to 1 in 5,000. 38 However, there are challenges to the robustness and yield of this as a screening tool.…”

“…38 However, there are challenges to the robustness and yield of this as a screening tool. [36][37][38][39] A negative newborn screen does not exclude acquired vitamin B12 deficiency. 33,40 Tier 1 neonatal screening has the potential to detect abnormal C3 concentrations as an indicator of cobalamin deficiency.…”

“…However, C3 levels have poor diagnostic sensitivity in the newborn period. [36][37][38][39][40][41] Expanded newborn screening programs have the potential to provide an improved yield from newborn screening, through second-tier assays which detect abnormalities in MMA, homocysteine, and 2-methylcitric acid levels by liquid chromatography-tandem mass spectrometry, which are collectively more sensitive indicators of cobalamin deficiency. 39,41 Finally, we recommend long-term follow-up of this group of infants in view of the higher risk of neuropsychological difficulties that may become more apparent through school age, and to ensure their needs can be better-supported.…”

Vitamin B12 deficiency in newborns and infants—Causes, early detection, diagnostics and presentation of a primary oral treatment scheme

“…Beim Kind führt ein schwerer, unerkannter Vitamin-B12-Mangel zu irreversiblen neurologischen Schädigungen und einer dauerhaften Entwicklungsstörung, die meist erst im zweiten Lebenshalbjahr klinisch erkannt wird [7,14,27]. Patienten mit Vitamin-B12-Mangel, die erst symptomatisch diagnostiziert werden, zeigen nach Beginn der Supplementation mit Vitamin B12 zwar eine Besserung der Symptome, die neurologischen und intellektuellen Langzeitergebnisse dieser Patienten belegen aber häufig deutliche bleibende Beeinträchtigungen [3,7,14,23]. Wird ein Vitamin-B12-Mangel hingegen früh präsymptomatisch erkannt und erfolgen therapeutische Gaben von Vitamin B12, kann dem Kind durch die frühe Behandlung eine normale Entwicklung ermöglicht werden.…”