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.
Highlights
Transcobalamin II (TC) deficiency is a rare autosomal recessive disease in early infancy caused by mutations in the TCN2 gene [1]
Transcobalamin II deficiency should be considered in the differential diagnosis of infants with immunological abnormalities as well as cytopenia and neurological dysfunction
Recognition of this rare condition and initiation of adequate treatment is critical for control of the disease and better prognosis
Summary
Transcobalamin II (TC) deficiency is a rare autosomal recessive disease in early infancy caused by mutations in the TCN2 gene [1]. TC is a transport protein for vitamin B12 and facilitates its cellular uptake by receptor-mediated endocytosis [1]. A deficiency of TC results in a lack of vitamin B12 entry into cells, leading to intracellular cobalamin depletion [2]. The presenting clinical features are failure to thrive, diarrhea, pancytopenia, neurologic abnormalities, and infections due to immunodeficiency [3,4,5,6]. The diagnosis is suspected based on the presence of clinical and laboratory features [5]. Treatment with parenteral vitamin B12 is highly effective on clinical and biological signs. It is important to establish the diagnosis of TC deficiency as early as possible because with a significant delay in diagnosis, and treatment, the neurological abnormalities can become irreversible [8]
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