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Monday, 18 August 2003
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Homocystinemia, Cystathionine Beta Synthase Deficiency


Homocystinuria is a metabolic disease where there is a problem breaking down a protein called methionine in the body. Proteins are made of amino acids and are necessary for our bodies to grow. Methionine is an example of an amino acid and is naturally found in food. During normal methionine metabolism (or breakdown), a compound called homocysteine is formed. This compound is usually converted to another compound called cysteine or recycled back to methionine. Thus, homocysteine normally remains in very small levels in the body. Patients affected with homocystinuria, however, cannot convert homocysteine to cysteine. This conversion is carried out by an enzyme called “cystathionine beta synthase”. Patients with homocystinuria are deficient in this enzyme. As a result, homocysteine as well as methionine builds up to dangerously high levels in the body.


Homocystinuria is a genetic disease that affects both children and adults. Individuals are born with the disorder, and symptoms usually manifest after 3 years of age. In the United States, approximately 1 out of every 200,000 to 300,000 individuals has homocystinuria. The prevalence in Ireland, Great Britain, and Australia is higher at an incidence of 1 in 65,000 to 82,000 live births.

Signs and Symptoms

Newborn infants with homocystinuria usually appear normal, although they may present with mildly delayed development or failure to thrive (poor growth). After 3 years of age, these children have visual problems such as nearsightedness and/or dislocated lenses (a part of the inner eye slips out of its normal position). Children with homocystinuria may exhibit some or all of the following symptoms:

  1. A family history with other members having homocystinuria.
  2. Nearsightedness.
  3. Displacement of the lens of the eye.
  4. Developmental delay. (Takes longer than normal to start sitting up, crawling, or walking).
  5. Mental retardation. (Note: Some affected people may have normal IQs).
  6. Psychiatric disease.
  7. Osteoporosis. (Thin, weak bones that may break easily).
  8. Physical appearance: Tall, thin body with long arms and legs. Long, thin fingers. Deformed chest. Feet with high arches. Knock-knees. Scoliosis (curved spine).
  9. Eye problems: Astigmatism, glaucoma, cataracts, retinal detachment, and optic atrophy.
  10. A history of frequent blood clots.

Possible Causes

All of us have genetic material that makes us who we are. The genetic material, referred to as “chromosomes” are numbered. The gene for homocystinuria has been found on chromosome 21 called the CBS gene. Mistakes in this gene cause homocystinuria. Homocystinuria is an autosomal recessive disorder. This means that each parent has one abnormal gene on chromosome 21 and one normal gene on chromosome 21. Because each parent has one normal gene, they themselves do not have homocystinuria. However, when the child receives one abnormal gene from the mother and one abnormal gene from the father, the child has two affected genes on chromosome 21. In autosomal recessive diseases, when a person has two abnormal genes, they are affected with disease, in this case, homocystinuria. This genetic change causes individuals with homocystinuria to be deficient in an enzyme called cystathionine beta synthase, which is important in the breakdown of the amino acid methionine. As a result, methionine and homocysteine build up in the body, as explained previously.


Diagnosis for homocystinuria involves a physical examination, an ophthalmological (eye) exam, and laboratory tests. A physical examination may reveal a tall, thin build with a deformed chest and curved spine. An ophthalmologist (eye doctor) may find a dislocated lens of the eye and nearsightedness. A skeletal x-ray may be taken to show osteoporosis. Blood and urine tests may be taken to check if methionine and homocysteine levels are high. If needed, a liver biopsy and enzyme studies may be taken to see if the enzyme cystathionine beta synthase is deficient. Genetic testing is available to analyze the gene responsible for cystathionine beta synthase.


While there is no known cure for homocystinuria, many patients do respond well to high doses of vitamin B6. Taking vitamin B6 is needed lifelong. If vitamin B6 does not work, individuals will need to be placed on a low methionine diet in conjunction with certain medications. For all patients with homocystinuria, folic acid and cysteine supplements can also help. Other treatment will depend on what symptoms the affected individual has. For example, an ophthalmologist can manage eye problems such as nearsightedness. A dislocated lens may require a lens replacement surgery. Medications may be used to help osteoporosis and blood clots. Psychiatrists can help treat psychiatric disorders. Infant and school programs can help with development and allow children to reach their fullest potential.


The prognosis for individuals with homocystinuria is variable depending on what symptoms they have. For example, symptoms such as blood clots can be life threatening. If diagnosis is made early and treatment is started promptly, mental retardation may be lessened.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


National Coalition for PKU and Allied Disorders
A comprehensive website designed for patients and their families. The website includes information on HCU, links to ongoing research, support groups, and other resurces, as well as low protein food sources and recipes.

Medline Plus
A great article written in easy to read language.

Google Search for Homocystinuria

References and Sources

Behrman, R., Kliegman, R., and H. Jenson. Nelson Textbook of Pediatrics. W.B. Saunder Co. 16th edition. 2000. pp. 350-352. MedlinePlus: Homocystinuria