What is homocystinuria?

What is homocystinuria?
Homocystinuria is an inherited disorder in which the body is unable to process certain building blocks of proteins (amino acids) properly. The most common form of the condition is caused by the lack of an enzyme called cystathionine beta-synthase. This form of homocystinuria is characterized by dislocation of the lens in the eye, an increased risk of abnormal blood clots, and skeletal abnormalities. Problems with development and learning are also evident in some cases.

Less common forms of homocystinuria are caused by a lack of other enzymes involved in processing amino acids. These disorders can cause intellectual disability, seizures, problems with movement, and a blood disorder called megaloblastic anemia.

How common is homocystinuria?
Homocystinuria caused by cystathionine beta-synthase deficiency 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 3,000). Other forms of homocystinuria are much rarer, with a small number of cases reported in the scientific literature.

What genes are related to homocystinuria?
Mutations in the CBS, MTHFR, MTR, and MTRR genes cause homocystinuria.

The CBS gene provides instructions for producing cystathionine beta-synthase. This enzyme is responsible for one step in a chemical pathway that processes the amino acid methionine. Other amino acids, including homocysteine, are also products of this pathway. 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 other potentially toxic substances build up in the blood, and 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, and MTRR genes play roles in converting homocysteine back 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.

Read more about the CBS, MTHFR, MTR, and MTRR genes.

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 vitamin B12 and folic acid deficiencies.

Where can I find information about treatment for homocystinuria?
These resources address the management of homocystinuria and may include treatment providers.

Gene Review: Disorders of Intracellular Cobalamin Metabolism
Gene Review: Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency
MedlinePlus Encyclopedia: Homocystinuria
You might also find information on treatment of homocystinuria in Educational resources and Patient support.

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.

MedlinePlus - Health information (3 links)
Educational resources - Information pages (12 links)
Patient support - For patients and families (3 links)
You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary (2 links)
Gene Tests - DNA tests ordered by healthcare professionals (3 links)
ACTion Sheets - Newborn screening follow up (1 link)
ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
OMIM - Genetic disorder catalog (4 links)
What if I still have specific questions about homocystinuria?
See How can I find a genetics professional in my area? in the Handbook.
Ask the Genetic and Rare Diseases Information Center.
Submit your question to Ask the Geneticist.
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.

Genetics and health
Resources for Patients and Families
Resources for Health Professionals
What glossary definitions help with understanding homocystinuria?
acids ; amino acid ; anemia ; autosomal ; autosomal recessive ; cell ; compound ; deficiency ; dislocation ; enzyme ; gene ; megaloblastic anemia ; mutation ; newborn screening ; protein ; recessive ; reductases ; screening ; seizure ; sign ; symptom ; toxic ; vitamin B12 ; vitamins

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

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