Transcobalamin II deficiency at birth

Ratschmann, Rene; Minkov, Milen; Kis, Ana; Hung, Christina; Rupar, Tony; Mühl, Adolf; Fowler, Brian; Nexø, Ebba; Bodamer, Olaf A.

doi:10.1016/j.ymgme.2009.06.003

Cited by 25 publications

(24 citation statements)

References 35 publications

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“…17 Extremely rare mutations in the TCN2 gene may result in severe intracellular cobalamin depletion. 18 More work needs to be done to sort out the genetics and pathophysiology related to cobalamin deficiency. 19 Some, but not all, studies have found marginally better performance (as assessed by receiver operator curves) by holoTC when compared with serum B 12 .…”

Section: Discussionmentioning

confidence: 99%

Laboratory Evaluation for Vitamin B12 Deficiency: The Case for Cascade Testing

Berg

Shaw

2012

Clinical Medicine & Research

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Section: Discussionmentioning

confidence: 99%

Laboratory Evaluation for Vitamin B12 Deficiency: The Case for Cascade Testing

Berg

Shaw

2012

Clinical Medicine & Research

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“…Molecular studies in the parents of each patient confirmed Mendelian inheritance. The previously reported mutations are varied, with nonsense mutations (Li et al 1994a;Prasad et al 2008), deletions (Haberle et al 2009;Li et al 1994a;Li et al 1994b), insertions (Ratschmann et al 2009), RNA editing (Qian et al 2002), and splice-site mutations (Haberle et al 2009;Namour et al 2003), all giving rise to truncated proteins. We also observed nucleotide deletions or duplications predicted to give rise to abnormal proteins.…”

Section: Discussionmentioning

confidence: 99%

“…About 45 TC-deficient patients have been reported (Kaikov et al 1991;Rosenblatt and Fenton 2001). The gene coding for TC (TCN2) was identified in 1995 (Regec et al 1995), and ten pathogenic mutations have further been reported (Haberle et al 2009;Li et al 1994a;Li et al 1994b;Namour et al 2003;Prasad et al 2008;Qian et al 2002;Ratschmann et al 2009). We report herein on five TCdeficient patients who exhibited six unreported TCN2 mutations defining two important coding regions in exons 4 and 8, which code for TC-TC receptor and TC-Cbl interaction domains, respectively.…”

Section: Introductionmentioning

confidence: 99%

Should transcobalamin deficiency be treated aggressively?

Schiff

Baulny²,

Bard³

et al. 2010

J of Inher Metab Disea

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Transcobalamin (transcobalamin II, TC) transports plasma vitamin B(12) (cobalamin, Cbl) into cells. TC deficiency is a rare autosomal recessive disorder causing intracellular Cbl depletion, which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid, and methionine depletion. The clinical presentation reflects intracellular Cbl defects, with early-onset failure to thrive with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia, sometimes followed by neurological complications. We report the clinical, biological, and molecular findings and the outcome in five TC-deficient patients. The three treated early had an initial favorable outcome, whereas the two treated inadequately had late-onset severe neuro-ophthalmological impairment. Even if the natural course of the disease over time might also result in late-onset symptoms in the aggressively treated patients, these data emphasize that TC deficiency is a severe disorder requiring early detection and probably long-term aggressive therapy. Mutation analysis revealed six unreported mutations in the TCN2 gene. In silico structural analysis showed that these mutations disrupt the Cbl-TC interaction domain and/or the putative transcobalamin-transcobalamin receptor interaction domain.

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“…The condition leads to severe Cbl deficiency most often diagnosed within the first year of life [11,12], and is caused by mutations in the TCN2 gene. So far, small insertion/deletion variants (indels), large deletions and mutations leading to exon skipping have been identified in TC deficient patients [13].…”

Section: Introductionmentioning

confidence: 99%

False low holotranscobalamin levels in a patient with a novel TCN2 mutation

Keller

Rufener

Schild

et al. 2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background: Measurement of holotranscobalamin (holoTC) is increasingly used as a screening test for cobalamin (Cbl) deficiency. A level well below the reference interval strongly supports a deficient state. We examined a 21-year-old woman diagnosed as Cbl deficient because of an extremely low holoTC level as measured by the Abbott Architect Assay. Methods: The patient was evaluated for Cbl deficiency employing an in-house holoTC method as well as other routine markers of Cbl status. Further analyses included exploration of the Cbl binding proteins employing gel filtration of a serum sample saturated with 57 Co-labeled Cbl and Sanger sequencing of exons 1-9 and the intron-exon boundaries of the TCN2 gene, the gene coding for transcobalamin (TC). Results: The patient had normal hematological variables throughout. Despite initial treatment with Cbl, holoTC as measured by the Abbott assay remained low, while holoTC measured with the in-house assay was normal, and behaved as TC upon gel-filtration. By Sanger sequencing, we detected a homozygous single point mutation c.855T > A in exon 6 of TCN2, corresponding to a asparagine (Asn) to lysine (Lys) substitution in position 267 of the mature protein. Conclusions:We describe a novel point mutation of the TCN2 gene. The mutation does not seem to interfere with

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Transcobalamin II deficiency at birth

Cited by 25 publications

References 35 publications

Laboratory Evaluation for Vitamin B12 Deficiency: The Case for Cascade Testing

Laboratory Evaluation for Vitamin B12 Deficiency: The Case for Cascade Testing

Should transcobalamin deficiency be treated aggressively?

False low holotranscobalamin levels in a patient with a novel TCN2 mutation

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