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

Abstract

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.

12 Survival-related differentially expressed genes based on the TARGET-osteosarcoma database

“…Intriguingly, mutation (loss of function) of this gene result in transcobalamin deficiency that leads to an abnormal immunity in the individuals. 39 Our result showed that down regulation of TCN2 is associated with worse survival outcome (Figure 3(h)).…”

A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency

“…Later, when transcobalamin defect and its associated increased homocysteine level was suspected, plasma homocysteine level was measured using a separate specific test. Less than 60 patients and 50 TCN2 variants have been reported worldwide in which many cases were reported from regions with a high rate of consanguinity, including Turkey [1,2,[11][12][13][14]. To our knowledge, the present patient is the first case report from a Southeast Asian country with a novel TCN2 variant, c.428-2A > G. The variant was subsequently submitted to ClinVar database and now is accessible using a number SCV001981507 (https:// www.…”

Comparison of TCN-2 (776C>G) Gene Polymorphism and Vitamin B12 Status with Different Body Mass Index among Saudi Adults

“…Nongmaithem SS et al observed that variants in the B12-binding protein gene TCN-2 have also been linked to circulating B12 levels [ 38 ], and that vitamin B12 bioavailability is controlled by the TCN-2 gene [ 39 ]. Alteration in TCN-2 is a mechanism that contributes to the pathogenesis of transcolabamin deficiency, and currently, many cases of transcolabamin deficiency have been reported worldwide [ 40 ], with only one case from China [ 41 ]. According to existing research, the existence of a TCN-2 (CG + GG) variation has been linked to an increased chance of developing Crohn’s disease [ 42 ].…”