Homocystinuria

Homocystinuria is an inherited disorder. It affects the metabolism of amino acids that contain sulfur. Amino acids are the building blocks of protein. Two amino acids that contain sulfur are methionine (MET) and homocysteine (which is derived from MET). People with Homocystinuria lack enzymes that the body needs to properly break down sulfur-containing amino acids. A deficiency in any of several enzymes can lead to the disorder. In the most common form of the disorder, there is a deficiency of the enzyme cystathionine synthetase. Due to the enzyme deficiency, the body cannot properly metabolize MET and homocysteine. The result is impaired growth, development, and tissue repair. A form of the excess homocysteine appears in the urine and blood.

Causes

Homocystinuria is caused by an autosomal recessive trait. This means that it occurs when a child inherits two defective genes—one from each parent.

Risk Factors

A risk factor is something that increases your chances of getting a disease or condition. A child is only at risk for this disorder if both parents are carriers of the faulty gene that causes it.
If bth parents carry the faulty gene, for each child, there is a:
  • 25% chance the child will be born with the disorder
  • 50% chance the child will be a carrier of the faulty gene

Symptoms

The number and severity of symptoms varies among people.
Infants with the disorder:
  • Grow and gain weight at a slower than normal rate (called failure to thrive)
  • Have developmental delays
After age three, more specific symptoms develop. The most common is eye problems. These include:
  • Lens dislocation
  • Severe nearsightedness (myopia)
Less common eye-related symptoms include:
  • Cataracts
  • Glaucoma
  • Retinal detachment
Other symptoms may include:
  • Osteoporosis
  • Flush across the cheeks
  • Heart disease
  • Vascular disease, such as:
    • Hardening of the arteries
    • Blood clots
    • Stroke
  • Progressive mental retardation
  • Mental illness
  • Seizures
  • Specific body features, including:
    • Tall, thin build
    • Chest deformities
    • Long limbs
    • Long, thin fingers
    • High-arched feet
    • Knock knees
    • Scoliosis

Diagnosis

Many states require that newborns be tested for Bomocystinuria before they leave the hospital. The test usually looks for high levels of MET. If the test is positive, blood or urine tests can be done to confirm the diagnosis. These tests can detect high levels of MET, homocystine, and other sulfur-containing amino acids. Tests to detect an enzyme deficiency (such as cystathionine synthetase) can be done as well.
If a child is not tested at birth, a doctor may later discover the disorder based on symptoms. At this point, the following may be done:
  • Blood tests to confirm the diagnosis
  • X-rays to look for bone problems
  • An eye exam to look for eye problems

Treatment

Treatment should begin as early as possible. Treatment may include medication and/or a special diet.
Medication About half of all children with Homocystinuria will respond to high doses of pyridoxine (vitamin B6). In some cases, vitamin B12, folate, or betaine may be prescribed to help prevent build-up of homocysteine in the blood. The drug trimethylglycine may be useful in some severe cases.
Special Diet A special diet may help people who don't respond to or don't respond fully to vitamin B6 treatment. Starting the diet early in life can help prevent mental retardation and other complications. In general, the diet:
  • Restricts foods with MET
  • Consists mainly of fruits and vegetables
  • Allows very little, if any, meats, eggs, dairy products, breads, and pastas
  • Is supplemented with:
    • Cysteine (an amino acid)
    • Folate

Prevention

There are no known ways to prevent Homocystinuria once a person is born. If you have a family history of Homocystinuria or carry the gene for Homocystinuria you can talk to a genetic counselor before deciding whether or not to have children.