homocystinuria, CBS-related

What Is Homocystinuria, CBS-Related?

Homocystinuria is an inherited metabolic condition where there is excessive homocysteine in the body. Classic homocystinuria is caused by cystathionine beta-synthase deficiency (CBS deficiency) due to a mutation in the CBS gene. People with classic homocystinuria are missing an enzyme called cystathionine beta-synthase which typically breaks down excessive homocysteine.

Homocystinuria can cause problems for many parts of the body. Infants with homocystinuria may have trouble growing and gaining weight. Eye problems may include nearsightedness and lens dislocation (ectopia lentis). People with homocystinuria can have skeletal problems such as curved spines (scoliosis) and fragile bones (osteoporosis). They can be taller and thinner than their siblings due to these bone changes. Homocystinuria can also cause abnormal blood clots (thromboembolisms). If these blood clots form in or travel to the heart, brain, or other vital organs, they can cause death. Some people with homocystinuria will have intellectual disability, which can range from mild to profound. About half of people who have homocystinuria will also have neurological or psychiatric problems such as seizures, behavioral disturbances, and mood problems.

Some people with homocystinuria respond to treatment with vitamin B6 (pyridoxine). These individuals usually have milder symptoms than people who do not respond to treatment with vitamin B6.

How Common Is Homocystinuria, CBS-Related?

The prevalence of homocystinuria is estimated at 1 in 250,000 people worldwide. Studies have suggested that the condition may be more common in Ireland, Germany, Norway, and Qatar. Most cases of homocystinuria are caused by mutations in CBS.

How Is Homocystinuria, CBS-Related Treated?

Treatment for people with homocystinuria is aimed at keeping the amount of homocysteine in the body low. Doctors will often recommend a diet low in methionine (which can turn into homocysteine in the body), which should be followed for life. Vitamin B6 can be helpful to some people with homocystinuria. A drug called betaine can also help reduce homocysteine levels. Other supplementation may include vitamin B12 (cobalamin) or vitamin B9 (folate). A person with homocystinuria will need to be in treatment for life.

In order to lower the risk of blood clots, people with the disease should avoid unnecessary surgery. Women should avoid oral contraceptives if possible. Women with the disease who become pregnant should work with their doctor to manage clotting risks associated with pregnancy. Surgery may be needed to correct dislocated eye lenses.

What Is the Prognosis for a Person with Homocystinuria, CBS-Related?

It is important that people with homocystinuria be diagnosed as soon as possible. Infants should begin treatment immediately to prevent or reduce the symptoms that occur when there are increased amounts of homocysteine in the body.

Without treatment, life expectancy for people with homocystinuria is often reduced. Blood clots are a major cause of early death in people who have homocystinuria. With lifelong treatment, the outcome for a person with homocystinuria is improved.