Transcobalamin (TC) deficiency and newborn screening

Prasad, Chitra; Cairney, A.E.L.; Rosenblatt, David S.; Rupar, C. Anthony

doi:10.1007/s10545-011-9431-4

Cited by 10 publications

(4 citation statements)

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“…There is one patient in our cohort who was identified by NBS using tandem mass spectrometry suggesting that TC deficiency may be identifiable by NBS. The flagged values were C3 and C3/C2 acylcarnitine elevation (Prasad et al 2008;2012). For reproductive counselling of parents with a previously The collected data suggest that both the age at commencement of Cbl treatment and its mode of administration influence outcome.…”

Section: Discussionmentioning

confidence: 99%

Update on transcobalamin deficiency: clinical presentation, treatment and outcome

Trakadis

Alfares

Bodamer

et al. 2013

J of Inher Metab Disea

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Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is treatable with supplemental cobalamin, but the optimal type, route and frequency of cobalamin administration and long term patient outcomes are unknown. Here we present a series of 30 patients with TC deficiency, including an update on multiple previously published patients, in order to evaluate the different treatment strategies and provide information about long term outcome. Based on the data presented, current practice appears to favour treatment of individuals with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In most cases presented, at least weekly injections (1 mg IM) were necessary to ensure optimal treatment. Most centres adjusted the treatment regimen based on monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid, as well as, clinical status. Finally, continuing IM treatment into adulthood appears to be beneficial.

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Section: Discussionmentioning

confidence: 99%

Update on transcobalamin deficiency: clinical presentation, treatment and outcome

Trakadis

Alfares

Bodamer

et al. 2013

J of Inher Metab Disea

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“…TC II deficiency has also been reportedly identified by tandem mass spectrometry. The flagged values were for C3 and C3/C2 acyl carnitine elevations [27]. However, these reports are not entirely consistent [19].…”

Section: Discussionmentioning

confidence: 98%

Identification of transcobalamin deficiency with two novel mutations in the TCN2 gene in a Chinese girl with abnormal immunity: a case report

Zhan

Cheng

et al. 2020

BMC Pediatr

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Background Transcobalamin (TC) transports vitamin B12 from blood into cells. TC II deficiency is a rare autosomal recessive disorder. It is characterized by failure to thrive, diarrhoea, pallor, anaemia, pancytopenia or agammaglobulinemia. It is usually confirmed by molecular analysis of the TCN2 gene. We report a 2-month-old girl with two novel mutations, which were first reported in humans. Case presentation We present a 2-month-old Chinese girl with pancytopenia, severe combined immunodeficiency disease, and megaloblastic anaemia. Targeted next-generation sequencing (NGS) was performed, which detected compound heterozygous variants in exon 7 of the TCN2 gene (Mutation 1: c.1033 C > T; Mutation 2: c.1017-1031delinsGTAACAGAGATGGTT). These mutations result in stop codons in TCN2. The c.1033C > T mutation causes a stop at codon 345 (p.Gln345Ter), and the c.1017-1031delinsGTAACAGAGATGGTT mutation causes a stop at codon 340 (p.Leu340Ter). After being diagnosed, she was treated with intramuscular 1 mg hydroxycobalamin (OH-Cbl) every day for 2 months. The CBC value returned to normal after half a month. The peripheral blood lymphocyte subsets and immunoglobulin recovered after 2 months. Then, the dosage of OH-Cbl was gradually reduced. Conclusions TC II deficiency is a serious complication that requires lifelong treatment. Its diagnosis is difficult due to the lack of clearly identifiable symptoms. Genetic testing should be performed as early as possible if this disease is suspected. The specific observations of this case report make a considerable contribution to the literature and provide a reference for the diagnosis and treatment of future cases.

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“…In view of severe but reversible nature of systemic effects which includes pancytopaenia, immune deficiency and neuro-regression, there is a case for newborn screening (NBS) for TC deficiency. It has been shown that elevation of C3 acyl-carnitine may help as an NBS tool 11. However the reports are inconsistent 7.…”

Section: Discussionmentioning

confidence: 99%

Transcobalamin deficiency: vitamin B₁₂deficiency with normal serum B₁₂levels

2019

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Transcobalamin (TC) deficiency is a rare autosomal recessive inborn error of cobalamin transport which clinically manifests in early infancy. We describe a child with TC deficiency who presented with classical clinical and lab stigmata of inborn error of vitamin B12 metabolism except normal serum B12 levels. He was started on empirical parenteral cobalamin supplements at 2 months of age; however, the definitive diagnosis could only be established at 6 years of age when a genetic evaluation revealed homozygous nonsense variation in exon 8 of the TCN2 gene (chr22:g.31019043C>T).

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Transcobalamin (TC) deficiency and newborn screening

Cited by 10 publications

References 2 publications

Update on transcobalamin deficiency: clinical presentation, treatment and outcome

Update on transcobalamin deficiency: clinical presentation, treatment and outcome

Identification of transcobalamin deficiency with two novel mutations in the TCN2 gene in a Chinese girl with abnormal immunity: a case report

Transcobalamin deficiency: vitamin B₁₂deficiency with normal serum B₁₂levels

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Transcobalamin (TC) deficiency and newborn screening

Cited by 10 publications

References 2 publications

Update on transcobalamin deficiency: clinical presentation, treatment and outcome

Update on transcobalamin deficiency: clinical presentation, treatment and outcome

Identification of transcobalamin deficiency with two novel mutations in the TCN2 gene in a Chinese girl with abnormal immunity: a case report

Transcobalamin deficiency: vitamin B12deficiency with normal serum B12levels

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Transcobalamin deficiency: vitamin B₁₂deficiency with normal serum B₁₂levels