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Reviewed July 2011
What is homocystinuria?
Homocystinuria is an inherited disorder in which the body is unable to process certain building blocks of proteins (amino acids) properly. There are multiple forms of homocystinuria, which are distinguished by their signs and symptoms and genetic cause. The most common form of homocystinuria is characterized by nearsightedness (myopia), dislocation of the lens at the front of the eye, an increased risk of abnormal blood clotting, and brittle bones that are prone to fracture (osteoporosis) or other skeletal abnormalities. Some affected individuals also have developmental delay and learning problems.
Less common forms of homocystinuria can cause intellectual disability, failure to grow and gain weight at the expected rate (failure to thrive), seizures, problems with movement, and a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic).
The signs and symptoms of homocystinuria typically develop within the first year of life, although some people with a mild form of the disease may not develop features until later in childhood or adulthood.
How common is homocystinuria?
The most common form of homocystinuria affects at least 1 in 200,000 to 335,000 people worldwide. The disorder appears to be more common in some countries, such as Ireland (1 in 65,000), Germany (1 in 17,800), Norway (1 in 6,400), and Qatar (1 in 1,800). The rarer forms of homocystinuria each have a small number of cases reported in the scientific literature.
What genes are related to homocystinuria?
Mutations in the CBS, MTHFR, MTR, MTRR, and MMADHC genes cause homocystinuria.
Mutations in the CBS gene cause the most common form of homocystinuria. The CBS gene provides instructions for producing an enzyme called cystathionine beta-synthase. This enzyme acts in a chemical pathway and is responsible for converting the amino acid homocysteine to a molecule called cystathionine. As a result of this pathway, other amino acids, including methionine, are produced. Mutations in the CBS gene disrupt the function of cystathionine beta-synthase, preventing homocysteine from being used properly. As a result, this amino acid and toxic byproducts substances build up in the blood. Some of the excess homocysteine is excreted in urine.
Rarely, homocystinuria can be caused by mutations in several other genes. The enzymes made by the MTHFR, MTR, MTRR, and MMADHC genes play roles in converting homocysteine to methionine. Mutations in any of these genes prevent the enzymes from functioning properly, which leads to a buildup of homocysteine in the body. Researchers have not determined how excess homocysteine and related compounds lead to the signs and symptoms of homocystinuria.
How do people inherit homocystinuria?
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.
Although people who carry one mutated copy and one normal copy of the CBS gene do not have homocystinuria, they are more likely than people without a CBS mutation to have shortages (deficiencies) of vitamin B12 and folic acid.
Where can I find information about diagnosis or management of homocystinuria?
These resources address the diagnosis or management of homocystinuria and may include treatment providers.
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 homocystinuria?
You may find the following resources about homocystinuria 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 homocystinuria?
What if I still have specific questions about homocystinuria?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding homocystinuria?
acids ; amino acid ; anemia ; autosomal ; autosomal recessive ; blood clotting ; cell ; clotting ; deficiency ; developmental delay ; disability ; dislocation ; enzyme ; failure to thrive ; gene ; megaloblastic anemia ; methionine ; molecule ; mutation ; myopia ; nearsightedness ; newborn screening ; osteoporosis ; recessive ; screening ; toxic ; vitamin B12
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (6 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.