Transcobalamin deficiency (Transcobalamin deficiency) - Gen TCN2.

Transcobalamin deficiency is a disorder that affects the transport of cobalamin (vitamin B12) inside the body. Cobalamin is obtained from the diet and is found in animal products such as meat, eggs and seafood. An inability to transport cobalamin in the body leads to cells lacking cobalamin. The absence of cobalamin causes alterations in growth, deficiency of blood cells, and many other signs and symptoms usually manifest in the first weeks or months of life.

The first signs of deficiency transcobalamin often stunted, vomiting, diarrhea and ulcers in the mucous membranes, such as oral. Also, neurological function in affected individuals, which may present as paraparesis, myoclonus, altered or intellectual disabilities. Often, people with transcobalamin deficiency develop megaloblastic anemia. In addition, individuals with this disease may also have neutropenia, which may lead to reduced immune system function. A decrease of cobalamin into cells can also lead to an accumulation of certain compounds in the body, generating metabolic disorders such as methylmalonic aciduria or homocystinuria.

This process is due to mutations in the gene TCN2, located on the long arm of chromosome 22 (22q12.2). This gene encodes the protein transcobalamin (formerly known as transcobalamin II). This protein carries cobalamin from the bloodstream to cells throughout the body, obtained through the diet. During digestion, cobalamin is transported through intestinal cells into the bloodstream. Transcobalamin aggregates bind cobalamin when released into the bloodstream and thus vitamin cells transported. The transcobalamin-cobalamin complex binds to a receptor on the cell surface, allowing the complex to enter the cell. Once the complex is inside the cell, cobalamin released transcobalamin and transcobalamin it decomposes. Inside the cells, cobalamin helps certain enzymes to carry out chemical reactions. Cobalamin plays a role in the processes that synthesize nucleotides and decompose various compounds such as fatty acids. These processes are needed for growth, proliferation and cellular energy production. The role of cobalamin in these processes is particularly important in the formation of new blood cells and the nervous system.

They have identified more than 20 mutations in the gene TCN2 leading to deficiency of transcobalamin. Many of these genetic mutations lead to an absence or deficiency of transcobalamin. Other mutations TCN2 gene, result in a transcobalamin protein can not bind to the cobalamin or a protein that can not bind to the receptor on the cell surface. The absence or cobalamin into cells interferes with the function of certain enzymes, affecting many cellular activities. As a result, you can develop a wide range of signs and symptoms of deficiency of transcobalamin.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with deficiency transcobalamin through the complete PCR amplification of exons TCN2 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).