Neonatal Vitamin B12 Deficiency Secondary to Maternal Subclinical Pernicious Anemia: Identification by Expanded Newborn Screening

Marble, Michael; Copeland, Sara; Khanfar, Nashat; Rosenblatt, David S.

doi:10.1016/j.jpeds.2008.01.023

Cited by 37 publications

(24 citation statements)

References 11 publications

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“…The expansion of newborn screening programmes to detect propionylcarnitine elevations has identified infants with deficiencies in the availability of vitamin B 12 (maternal B 12 deficiency, maternal subclinical pernicious anaemia and the cblC disorder) (Campbell et al 2005;Marble et al 2008). The detection of urinary MMA in the newborns as part of the newborn screening has also led to identification of maternal B 12 deficiency in a few centres (Michaud et al 1992).…”

Section: Discussionmentioning

confidence: 99%

Transcobalamin (TC) deficiency—Potential cause of bone marrow failure in childhood

Prasad

Rosenblatt

Corley

et al. 2008

J of Inher Metab Disea

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It is unusual for inborn errors of metabolism to be considered in the investigative work-up of pancytopenia. We report a family in which the proband presented with failure to thrive at 2 months of age and subsequent bone marrow failure. A previous sibling had died at 7 months of age with suspected leukaemia. Haematological findings in the proband were significant for pancytopenia, and bone marrow aspiration showed dysplastic changes in all cell lineages. Urinary organic acid analysis revealed elevated methylmalonic acid. The synthesis of transcobalamin II (transcobalamin, TC) by cultured fibroblasts was markedly reduced, confirming the diagnosis of TC deficiency. The proband and his younger asymptomatic sister (also found to have TC deficiency) were homozygous for R399X (c.1195C>T), a novel mutation resulting in the loss of the C- terminal 29 amino acids of TC, a highly conserved region. Response to parenteral vitamin B(12) in the proband was dramatic. At 6 years 3 months of age, physical examination is normal and developmental level is age appropriate. His sister is clinically asymptomatic and is also developing normally. Propionylcarnitine concentrations were not elevated in the newborn screening cards from the proband and sister, but that was for specimens retrieved from storage after 7 years and 5 years, respectively. Inherited and acquired cobalamin disorders should both be considered in the differential diagnosis of bone marrow failure syndromes in young children. Early detection of the metabolic causes of bone marrow failure can ensure prompt recovery in some cases involving the vitamin B(12) pathway.

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Section: Discussionmentioning

confidence: 99%

Transcobalamin (TC) deficiency—Potential cause of bone marrow failure in childhood

Prasad

Rosenblatt

Corley

et al. 2008

J of Inher Metab Disea

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“…In our retrospective study of the benign form of MMAU (Sniderman et al 1999), MMA levels of 5-10 nmol/ml were observed in DBS of two patients who were identified in newborn screening by GC/MS using urine (Kuhara et al 1999), whereas urinary levels of methylcitric acid and DBS levels of C3 were not elevated. Detection of neonatal vitamin B 12 deficiency by MS/MS newborn screening has been reported in newborns whose mothers had vitamin B 12 deficiency based on elevated C3, although MMA levels in DBS were not mentioned (Wiley et al 1999, Campbell et al 2005, Marble et al 2008. In our study, it is not clear whether newborns with falsepositive results had vitamin B 12 deficiency or not, as their serum vitamin B 12 concentrations were not determined.…”

Section: Discussionmentioning

confidence: 58%

Useful second‐tier tests in expanded newborn screening of isovaleric acidemia and methylmalonic aciduria

Shigematsu

Hata

Tanaka

2010

J of Inher Metab Disea

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Common use of pivalate-generating antibiotics in newborns in Japan and low cutoff value of C5-acylcarnitine (C5) to detect mild forms of isovaleric acidemia (IVA) led to 1,065 positive results from IVA screening among 146,000 newborns tested by tandem mass spectrometry over the last 3 years. Using our method to determine isovalerylglycine (IVG) levels in dried blood spots (DBS) as a second-tier test with IVG cutoff value of 0.5 nmol/ml in DBS, one patient with severe IVA was identified, and no recall of the second DBS was needed. Retrospective analysis revealed that most patients with moderate to severe forms of IVA have decreased free-carnitine levels shortly after birth and higher levels of IVG than those of C5, which suggests that this method is useful in evaluating the severity of IVA. Another second-tier test, to measure methylmalonic acid (MMA) levels in DBS by gas chromatography/mass spectrometry (GC/MS), has been developed to overcome difficulties in screening methylmalonic aciduria (MMAU) and propionic acidemia. Methanol extract from DBS was dried and derivatized using N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide. GC/MS was performed using splitless injection, electron-impact ionization, and selected ion monitoring for data recording. MMAU patients had much higher DBS concentrations of MMA (24.2-321.9 nmol/ml) than control newborns (0.34 ± 0.11 nmol/ml). MMA measurement in DBS was thought to provide useful information about the severity of MMAU, as MMAU patients with high levels of MMA had decreased levels of free carnitine and mildly increased levels of propionylcarnitine.

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“…In our case, exclusive breastfeeding associated with low levels of maternal cobalamin has conditioned a deficit state of this vitamin. The normal newborn has enough vitamin B 12 for 6–8 months,3 8 even in the presence of a restricted diet or inadequate absorption, so the signs and symptoms of disease occur after a normal developmental period,1 2 4 6 characteristically between the 4th and 8th months of age,1–3 8 as in this case.…”

Section: Discussionmentioning

confidence: 72%

“…Vitamin B 12 deficiency should always be considered in children with neurologic symptoms associated with megaloblastosis and failure to thrive8 and must be included in the differential diagnosis of failure to thrive, regression of psychomotor development and neurologic, psychiatric and haematologic manifestations 3 10. The confirmation of diagnosis is made by elevated urinary or serum methylmalonic acid and serum homocysteine levels and decreased vitamin B 12 serum levels 2 5 7 13. Methylmalonic acid, except when caused by inborn errors of metabolism,1 6 13 18 is the most sensitive and specific markers of preclinical vitamin B 12 deficiency2 3 5 6 8 13 18 and is a useful tool for differentiating from folate deficiency 18.…”

Section: Discussionmentioning

confidence: 99%

“…The confirmation of diagnosis is made by elevated urinary or serum methylmalonic acid and serum homocysteine levels and decreased vitamin B 12 serum levels 2 5 7 13. Methylmalonic acid, except when caused by inborn errors of metabolism,1 6 13 18 is the most sensitive and specific markers of preclinical vitamin B 12 deficiency2 3 5 6 8 13 18 and is a useful tool for differentiating from folate deficiency 18. Unfortunately, in this case, we have no data on urine methylmalonic acid before the beginning of the treatment.…”

Section: Discussionmentioning

confidence: 99%

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Severe megaloblastic anaemia in an infant

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Neonatal Vitamin B12 Deficiency Secondary to Maternal Subclinical Pernicious Anemia: Identification by Expanded Newborn Screening

Cited by 37 publications

References 11 publications

Transcobalamin (TC) deficiency—Potential cause of bone marrow failure in childhood

Transcobalamin (TC) deficiency—Potential cause of bone marrow failure in childhood

Useful second‐tier tests in expanded newborn screening of isovaleric acidemia and methylmalonic aciduria

Severe megaloblastic anaemia in an infant

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