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Reviewed October 2014
What is transcobalamin deficiency?
Transcobalamin deficiency is a disorder that impairs the transport of cobalamin (also known as vitamin B12) within the body. Cobalamin is obtained from the diet; this vitamin is found in animal products such as meat, eggs, and shellfish. An inability to transport cobalamin within the body results in cells that lack cobalamin, which they need for many functions including cell growth and division (proliferation) and DNA production. 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.
How common is transcobalamin deficiency?
The prevalence of transcobalamin deficiency is unknown. At least 45 affected individuals have been described in the medical literature.
What genes are related to transcobalamin deficiency?
Mutations in the TCN2 gene cause transcobalamin deficiency. The TCN2 gene provides instructions for making a protein called transcobalamin. This protein attaches (binds) to cobalamin and transports the vitamin to cells throughout the body. Within cells, cobalamin helps certain enzymes carry out chemical reactions. Cobalamin plays a role in the processes that produce the building blocks of DNA (nucleotides) and break down various compounds such as fatty acids; these processes are needed for cell proliferation and the production of cellular energy.
Most TCN2 gene mutations that cause transcobalamin deficiency lead to a complete or near-complete lack (deficiency) of transcobalamin. Other TCN2 gene mutations result in a transcobalamin protein that cannot transport cobalamin to cells. The resulting lack of cobalamin within cells interferes with the functioning of certain enzymes, which impacts many cell activities. As a result, a wide range of signs and symptoms can develop including impaired growth, blood cell shortages, and neurological problems.
Read more about the TCN2 gene.
How do people inherit transcobalamin deficiency?
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Where can I find information about diagnosis or management of transcobalamin deficiency?
These resources address the diagnosis or management of transcobalamin deficiency and may include treatment providers.
You might also find information on the diagnosis or management of transcobalamin deficiency inEducational resources and Patient support.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about transcobalamin deficiency?
You may find the following resources about transcobalamin deficiency helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for transcobalamin deficiency?
- TC deficiency
- TC II deficiency
- TCN2 deficiency
- transcobalamin II deficiency
What if I still have specific questions about transcobalamin deficiency?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
- What does it mean if a disorder seems to run in my family?
- What are the different ways in which a genetic condition can be inherited?
- If a genetic disorder runs in my family, what are the chances that my children will have the condition?
- Why are some genetic conditions more common in particular ethnic groups?
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding transcobalamin deficiency?
acids ; aciduria ; anemia ; autosomal ; autosomal recessive ; cell ; cell proliferation ; cobalamin ;deficiency ; disability ; DNA ; failure to thrive ; fatty acids ; gene ; immune system ; inherited ;megaloblastic anemia ; mucous ; myoclonus ; neurological ; neutropenia ; paraparesis ; prevalence ;proliferation ; protein ; recessive ; vitamin B12 ; white blood cells
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (5 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.