High incidence of low vitamin B12 levels in Estonian newborns

Abstract

Vitamin B12 deficiency seems to be more common worldwide than previously thought. However, only a few reports based on data from newborn screening (NBS) programs have drawn attention to that subject. In Estonia, over the past three years, we have diagnosed 14 newborns with congenital acquired vitamin B12 deficiency. Therefore, the incidence of that condition is 33.8/100,000 live births, which is considerably more than previously believed. None of the newborns had any clinical symptoms associated with vitamin B12 deficiency before the treatment, and all biochemical markers normalized after treatment, which strongly supports the presence of treatable congenital deficiency of vitamin B12. During the screening period, we began using actively ratios of some metabolites like propionylcarnitine (C3) to acetylcarnitine (C2) and C3 to palmitoylcarnitine (C16) to improve the identification of newborns with acquired vitamin B12 deficiency.In the light of the results obtained, we will continue to screen the congenital acquired vitamin B12 deficiency among our NBS program. Every child with aberrant C3, C3/C2 and C3/C16 will be thoroughly examined to exclude acquired vitamin B12 deficiency, which can easily be corrected in most cases.

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

“…Finally, to benchmark our screening strategy we compared the overall estimated detection rate of low VitB12 concentrations in newborns to other published reports ( Figure 6 ). Our estimated prevalence in the Austrian population of 93 in 100,000 newborns, which was 3–4 times higher compared to other reports [ 3 , 6 , 10 ].…”

“…In contrast, propionylcarnitine (C3) and methionine, which are metabolites in these metabolic pathways upstream and downstream of MMA and HCy, respectively, and indicative for B12D, albeit with low specificity, are commonly determined in expanded newborn screening. Therefore, based on published data [ 3 , 10 ], we developed a decision algorithm based on C3 and methionine and distinct ratios of these markers to select samples for measurement of tHCy as a second-tier marker ( Figure 1 ). Following a recent publication [ 12 ] and simultaneous with a change of the analytic instrument after 8 months of screening for suspected B12D, we adjusted the selection algorithm towards a higher number of samples selected via low methionine as well as a stronger emphasis on the C3/Met ratio ( Figure 1 ).…”

“…The decision algorithm for cobalamin deficiencies was built on the available published data from newborn screenings [ 3 , 10 , 11 ] and own experience while taking the throughput capabilities of our facility into consideration. In detail, samples for total HCy (tHCy) measurement were selected by elevated C3 and its ratios to C2, palmitoylcarnitine (C16), methionine, and free carnitine (C0) and lowered methionine or its ratio to phenylalanine (Phe).…”

FLAD1‐associated multiple acyl‐CoA dehydrogenase deficiency identified by newborn screening

“…In Estonia, newborn screening for phenylketonuria was introduced in 1993 (Ounap, Lillevali, Metspalu, & Lipping‐Sitska, ), and in 1996 screening for congenital hypothyroidism was added. In 2014, expanded neonatal screening was initiated and presently includes 19 treatable congenital metabolic diseases (Reinson et al, ). In this particular case, the abnormal newborn screening result was concerning for MCADD and/or MADD given the modest elevation of C4‐C10.…”

“…Organic acids from urine were measured by gas chromatography mass spectrometry (GC/MS) (Agilent 7890B GC with 977A MSD running on MassHunter software [Agilent Technologies]). All used reference intervals were age‐specific and based on the previous experience of the laboratory (Reinson et al, ).…”