Homocystinuria: Causes, symptoms, and tests

Methionine is an important amino acid in the body. Homocystinuria is characterized by an inability to breakdown methionine, causing numerous health problems.
Homocystinuria is a genetic disease that is passed on in an autosomal recessive manner. This process means two copies of an irregular gene must be present for a disease to develop.

In this article, we examine what homocystinuria is, what causes it, and what symptoms it produces. We also look at diagnosis and treatment of the disease.

What is homocystinuria?

In homocystinuria, the body is unable to breakdown certain proteins. Specifically, the condition affects an amino acid called methionine.

Amino acids are essential human building blocks. Methionine is a naturally occurring protein that babies need for growth and adults need for regulating nitrogen in the body. All amino acids contain nitrogen, making nitrogen an important part of human DNA.

There are several different forms of homocystinuria, which are set apart by their symptoms.

The most common form is called cystathionine beta-synthase (CBS). CBS differs from other types of homocystinuria because it causes the following symptoms:

  • nearsightedness
  • dislocation of the front eye lenses
  • increased blood clotting
  • brittle bones or other skeletal abnormalities

CBS can also cause developmental delays and learning disabilities.

Other less common forms of homocystinuria may cause a variety of other symptoms.


Doctor and patient.
Homocystinuria is most often diagnosed at birth or in infancy, as children are screened for the condition in the U.S. However, some forms of the condition may not be identified in the screening procedures.

In the United States, homocystinuria is screened for at birth. Screening does not detect all forms of homocystinuria and cases may remain undiagnosed for up to 5 years from birth.

It is believed homocystinuria affects about 1 out of every 200,000 to 300,000 babies born in the U.S., according to a division of the U.S. Department of Health and Human Services (HHS).

It is also more common in certain nationalities. For example, the HHS report that in the U.S., it is more common in white people from New England who are of Irish ancestry. In this group, the condition affects one in 50,000 newborns.

Worldwide, the most common type of homocystinuria affects 1 in 200,000 to 335,000 people, according to the National Institutes of Health. Furthermore, it appears to be more common in certain countries, including Germany, Norway, Ireland, and Qatar.

One study found six specific genetic mutations-related homocystinuria in a blood panel review of 1,133 newborns. These findings suggest that homocystinuria is more common than researchers previously believed.

Causes and risk factors

As homocystinuria is genetically autosomal recessive, a child must inherit two copies of the non-working gene for homocystinuria from each parent to develop the condition. Parents carrying the non-working gene may not have any symptoms of homocystinuria.

According to researchers, a child of a person carrying out the gene has:

  • a 25 percent chance of being affected by homocystinuria
  • a 50 percent of being a carrier
  • a 25 percent chance of being unaffected and carrying the gene


With most cases of homocystinuria, the enzyme cystathionine beta-synthase (CBS) does not work. As a result, the amino acids methionine and homocysteine cannot break down.

This causes high levels of both amino acids to build up throughout the body, which can be toxic and cause damage to the nervous system. Areas that can be damaged include the brain and the vessels carrying blood and lymph around the body.

The signs and symptoms of homocystinuria are evident in the first year of life. While some infants are mildly affected by homocystinuria, these symptoms may worsen as the individual progress into childhood and even adulthood.

Symptoms may include:

  • nearsightedness or dislocation of the lenses of the eyes
  • pale skin and hair
  • weak bones
  • sideways curvature of the spine
  • long and thin arms and legs
  • chest deformities
  • developmental delays and learning disabilities
  • behavioral problems

Symptoms that are less common include:

  • low red blood cell levels where the blood cells are a larger size than normal, known as megablastic anemia
  • failure in infants to grow and gain weight at expected rates
  • movement and gait problems
  • seizures

It is possible that many of these symptoms are worse when a baby consumes a food that their body cannot break down. They are also triggered by periods of illness and infection.


The most serious complication of homocystinuria is blood clots, which can be life-threatening and raise the risk of stroke.

Intellectual disability is also possible, but the risk can be reduced if homocystinuria is diagnosed early and treated successfully.

Dislocated lenses of the eyes can damage vision. Lens replacement surgery may be needed to help some people.

Diagnosing homocystinuria

Young woman at opticians.
Eye tests may help to identify some common symptoms of homocystinuria, such as nearsightedness and dislocated lenses.

Clear signs that may lead a doctor to test for homocystinuria is if a child is extremely thin and too tall for their age, or they are not growing as expected.

Additionally, the doctor will look for signs of chest deformity, spinal curvature, and dislocated eye lenses.

Eye exams may reveal vision problems, and X-rays may indicate signs of weak bones. Genetic testing, amino acid screening, liver biopsies, and liver enzyme tests are also used to make a diagnosis of homocystinuria.

Genetic testing

Researchers recommend genetic testing for anyone with a family history of homocystinuria who wants to have children.

However, because this condition is a result of genetic mutation, it cannot be prevented. The only reason for genetic testing is to give people some idea of the risk involved with having a gene mutation for homocystinuria.


There is no cure for homocystinuria although it can be treated with diet restrictions, supplements, and medication. High doses of B6 supplements have been helpful for some people, and most of those with the disease will need to take B6 supplements for the rest of their lives.

Those who do not respond to B6 treatments should follow a low-methionine diet. Examples of foods to avoid that contain high levels of the amino acid methionine include:

  • some meats and fish
  • eggs
  • soy
  • dairy
  • nuts and beans

Another treatment option is betaine, a nutrient that helps to remove the amino acid homocysteine from the bloodstream. Taking folic acid with betaine may also help.


People with homocystinuria can lead normal lives if they are diagnosed early enough and their treatment is successful. However, blood clots can cause health problems, and sometimes life-threatening complications.

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