How many types of transcobalamin deficiency are there

Suggest an update. Summary and related texts. Related genes. Clinical signs. To get in touch with the Orphanet team, please contact Information provided in your contribution including your email address will be stocked in. Check this box if you wish to receive a copy of your message. Disease definition Transcobalamin deficiency TC is a disorder of cobalamin transport that usually presents during the first few months of life and is characterized by megaloblastic anemia, failure to thrive, vomiting, weakness and pancytopenia.

Summary Epidemiology To date, more than 40 cases of TC have been described in the literature. Clinical description TC typically manifests in the first few months of life. Diagnostic methods Diagnosis is based on laboratory findings showing pancytopenia or isolated megaloblastic anemia or combined anemia and leucopenia and accumulation of homocysteine and methylmalonic acid.

Antenatal diagnosis Prenatal diagnosis is based on genetic screening of TCN2 or incubation of amniocytes in medium lacking any exogenous source of transcobalamin supplemented with radiolabeled cobalamin followed by measurement of transcobalamin-bound cobalamin. Genetic counseling Transmission is autosomal recessive. Prognosis TC is a severe, life-threatening and rapidly progressing disease.

The absence of cobalamin leads to impaired growth, a shortage of blood cells, and many other signs and symptoms that usually become apparent within the first weeks or months of life.

The first signs of transcobalamin deficiency are typically a failure to gain weight and grow at the expected rate failure to thrive , vomiting, diarrhea, and open sores ulcers on the mucous membranes such as the lining inside the mouth. Neurological function is impaired in affected individuals, and they can experience progressive stiffness and weakness in their legs paraparesis , muscle twitches myoclonus , or intellectual disability.

People with transcobalamin deficiency often develop a blood disorder called megaloblastic anemia. Megaloblastic anemia results in a shortage of red blood cells, and the remaining red blood cells are abnormally large. Individuals with transcobalamin deficiency may also have a shortage of white blood cells neutropenia , which can lead to reduced immune system function.

Decreased cellular cobalamin can lead to a buildup of certain compounds in the body, resulting in metabolic conditions known as methylmalonic aciduria or homocystinuria. MalaCards based summary : Transcobalamin Deficiency, also known as transcobalamin ii deficiency , is related to transcobalamin ii deficiency and transcobalamin i deficiency , and has symptoms including vomiting , lethargy and diarrhea.

Affiliated tissues include bone marrow , kidney and bone , and related phenotypes are abnormality of chromosome stability and methylmalonic aciduria Wikipedia : 72 Transcobalamins are carrier proteins which bind cobalamin Graphical network of the top 20 diseases related to Transcobalamin Deficiency:. Chorfi S Qian CX. Long-term outcome of a patient with Transcobalamin deficiency caused by the homozygous c.

Martino F Barilla F. Transcobalamin II deficiency in twins with a novel variant in the TCN2 gene: case report and review of literature. Kose E Isguder R. Identification of transcobalamin deficiency with two novel mutations in the TCN2 gene in a Chinese girl with abnormal immunity: a case report.

Zhan S Feng X. Immunodeficiency and inborn disorders of vitamin B12 and folate metabolism. Watkins D Rosenblatt DS. Transcobalamin deficiency: vitamin B12 deficiency with normal serum B12 levels. Khera S Patnaik SK. Unal S Kuyucu S. Sampagar A Bartakke S. Nashabat M Alfadhel M. Chao MM Kratz CP. Trilineage dyspoiesis caused by transcobalamin II deficiency. LX and p.

QX protein [ 23 , 24 , 25 ]. Both mutants showed loss of an unknown C-terminal domain with unknown function of transcobalamin, a vitamin Bbinding protein that transports cobalamin into cells Fig.

Protein structure prediction caused by compound heterozygous gene mutations of the TCN2 gene. LeuTer, the dashed box shows the lost C-terminal domain.

GlnTer; the dashed box shows the lost C-terminal domain. We report the case of a two-month-old baby girl with vomiting, diarrhoea, weight stagnation, pancytopenia and combined immunodeficiency. She received intensive care in the Paediatric Intensive Care Unit for three months. Tarkadis et al. Almost all these symptoms appear between 2 and 4 weeks after birth and worsen over approximately 2 months.

Early diagnosis is very difficult because there are no typical clinical manifestations of TC II deficiency, and multiple systems can be involved. The blood system is most often affected and could be an indication. However, several other diseases also lead to pancytopenia in a newborn or small baby. These include disorders that cause increased blood cell damage, such as systemic autoimmune disorders, immune dysregulation syndrome, systemic lupus erythematosus, disseminated intravascular coagulation, and hypersplenism, and those resulting in haematopoietic function failure include a variety of infections, infiltrative bone marrow diseases, and other genetic factors.

Among these, the most common is infection caused by Epstein-Barr virus, cytomegalovirus, chicken pox, rickettsia, and bacterial sepsis. TC II deficiency is extremely rare and prone to misdiagnosis. The diagnosis delay causes progressive deterioration in the patient and increases the chance of infection and the need for blood transfusion.

However, if the patient is diagnosed in the neonatal period and receives early treatment, there are chances of better prognosis, especially with respect to the development of the nervous system and growth. Therefore, early recognition and treatment of the disease are particularly important. With the development of diagnostic technology, at present, the diagnosis of this disease clearly depends on next-generation sequencing. TC II deficiency has also been reportedly identified by tandem mass spectrometry.

However, these reports are not entirely consistent [ 19 ]. Although there was no significant difference in efficacy between the two treatments, the mode of administration seemed to affect the prognosis, and intramuscular injection was recommended [ 19 ].

The patient requires treatment for life, and the most common complications include speech and attention disorders. The patient we described herein was prescribed 1 mg OH-Cbl intramuscularly every day on day , and her CBC value returned to normal after half a month.

After a treatment period of 2 months, OH-Cbl gradually changed to once every 4 weeks. As a result of earlier targeted treatment, she achieved good therapeutic effects. In summary, TC II deficiency is a rare autosomal recessive disorder that requires lifelong treatment. Early recognition and treatment of the disease is particularly important. This study reports two novel mutations in the TCN2 gene that result in mutated proteins with possible loss of function.

We believe that the specific observations made during this case report will provide a reference for the diagnosis and treatment of future cases. The datasets used during the current study are available from the corresponding author upon reasonable request.

Neonatal megaloblastic anemia due to inherited transcobalamin II deficiency in two siblings. N Engl J Med. The cloning and characterization of the human transcobalamin II gene. Assignment of human transcobalamin II TC2 to chromosome 22 using somatic cell hybrids and monosomic meningioma cells. Hum Genet. Identification of two mutant alleles of transcobalamin II in an affected family. Hum Mol Genet. Nonsense mutations in human transcobalamin II deficiency. Biochem Biophys Res Commun.

Transcobalamin II deficiency at birth. Mol Genet Metab. Transcobalamin deficiency due to activation of an intra exonic cryptic splice site. Br J Haematol. Watkins D, Rosenblatt DS. Inborn errors of cobalamin absorption and metabolism. Single nucleotide polymorphisms in the transcobalamin gene: relationship with transcobalamin concentrations and risk for neural tube defects.

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.