Different Presentations of Patients with Transcobalamin II Deficiency: A Single-Center Experience from Turkey

Abstract

Objective: Transcobalamin II deficiency is a rare autosomal recessive disease characterized by decreased cobalamin availability, which in turn causes accumulation of homocysteine and methylmalonic acid. The presenting clinical features are failure to thrive, diarrhea, megaloblastic anemia, pancytopenia, neurologic abnormalities, and also recurrent infections due to immune abnormalities in early infancy. Materials and Methods: Here, we report the clinical and laboratory features of six children with transcobalamin II deficiency who were all molecularly confirmed. Results: The patients were admitted between 1 and 7 months of age with anemia or pancytopenia. Unexpectedly, one patient had a serum vitamin B12 level lower than the normal range and another one had nonsignificantly elevated serum homocysteine levels. Four patients had lymphopenia, four had neutropenia and three also had hypogammaglobulinemia. Suggesting the consideration of transcobalamin II deficiency in the differential diagnosis of immune deficiency. Hemophagocytic lymphohistiocytosis was also detected in one patient. Furthermore, two patients had vacuolization in the myeloid lineage in bone marrow aspiration, which may be an additional finding of transcobalamin II deficiency. The hematological abnormalities in all patients resolved after parenteral cobalamin treatment. In follow-up, two patients showed neurological impairments such as impaired speech and walking. Among our six patients who were all molecularly confirmed, two had the mutation that was reported in transcobalamin II-deficient patients of Turkish ancestry. Also, a novel TCN2 gene mutation was detected in one of the remaining patients. Conclusion: Transcobalamin II deficiency should be considered in the differential diagnosis of infants with immunological abnormalities as well as cytopenia and neurological dysfunction. Early recognition of this rare condition and initiation of adequate treatment is critical for control of the disease and better prognosis.

Case report: Novel compound-heterozygous mutations in the TCN2 gene identified in a chinese girl with transcobalamin deficiency

“…In patients with TC deficiency, deletions are the most common variant, with insertions and variants at splicing sites rarely found. The majority (about 80%) of patients carried homozygous variants, while only a minority had compound-heterozygous variants (Schiff et al, 2010;Trakadis et al, 2014;Bartakke et al, 2015;Chao et al, 2017;Li and Goubeaux, 2017;Yildirim et al, 2017;Ünal et al, 2019). In this study, a pair of compound-heterozygous variants in TCN2 gene were identified, which is a very valuable case of TC deficiency.…”

“…It is well known that early and proper treatment is crucial for achieving optimal outcomes (Yildirim et al, 2017;Ünal et al, 2019;Zhan et al, 2020). Most studies showed that early and aggressive treatment, which includes parenteral or high-dose…”

“…(1 mg) i. m. (at least once a week), led to better outcomes (Yildirim et al, 2017;Ünal et al, 2019). Moreover, neurological and hematological deteriorations have been reported in patients who discontinued treatment (Yildirim et al, 2017;Ünal et al, 2019).…”

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.…”

Vasculitis associated with VEXAS syndrome: A literature review

“…The name “V”EXAS syndrome stems from “vacuoles” in myeloid and erythroid cells, but not in T lymphocytes, B lymphocytes, or fibroblasts ( 11 ). Of note, myeloid and erythroid vacuolization is not specific to VEXAS syndrome, but has been described in other disorders, including copper deficiency ( 39 ), acute myeloid leukemia ( 40 ), Menkes disease ( 41 ), and transcobalamin II deficiency ( 42 ).…”