Homocystinuria

Definition

Homocystinuria is an inherited disorder that affects the metabolism of the amino acid methionine.

Alternative Names

Cystathionine beta synthase deficiency

Causes, incidence, and risk factors

Homocystinuria is inherited in families as an autosomal recessive trait. This means that the child must inherit the defective gene from both parents to be seriously affected.

Homocystinuria has several features in common with Marfan syndrome. Unlike Marfan syndrome, in which the joints tend to be "loose," in homocystinuria the joints tend to be "tight."

Symptoms

Newborn infants appear healthy. Early symptoms, if present at all, are not obvious.

Symptoms may occur as mildly delayed development or failure to thrive. Increasing visual problems may lead to diagnosis of this condition.

Other symptoms include:

• Chest deformities (pectus carinatum, pectus excavatum)
• Flush across the cheeks
• High arches of the feet
• Knock knees
• Long limbs
• Mental retardation
• Nearsightedness
• Psychiatric disorders
• Spidery fingers (arachnodactyly)
• Tall, thin build

Signs and tests

While performing a physical examination on the child, the health care provider may notice a tall, thin (Marfanoid) stature.

Other signs include:

• Curved spine (scoliosis)
• Deformity of the chest
• Dislocated lens of the eye

If there is poor or double vision, an ophthalmologist should perform a dilated eye exam to look for dislocation of the lens or nearsightedness.

There may be a history of frequent blood clots. Mental retardation, slightly low IQ, or psychiatric disease are common.

Tests:

• Amino acid screen of blood and urine
• Genetic testing
• Liver biopsy and enzyme assay
• Skeletal x-ray
• Skin biopsy with a fibroblast culture
• Standard ophthalmic exam

Treatment

There is no cure for homocystinuria. However, many people respond to high doses of vitamin B6 (also known as pyridoxine). Slightly less than half of patients respond to this treatment.

Those who do respond will need to take supplemental vitamin B6 for the rest of their lives. Those who do not respond require a low methionine diet. Most will need treatment with trimethylglycine (a medication also known as betaine).

Neither a low-methionine diet nor medication will improve existing mental retardation. Medication and diet should be closely supervised by a physician with experience treating homocystinuria.

A normal dose folic acid supplement and added cysteine (an amino acid) in the diet is helpful.

Expectations (prognosis)

Although no cure exists for homocystinuria, vitamin B6 therapy can help about half of people affected by the condition.

If the diagnosis is made while a patient is young, starting a low methionine diet quickly can prevent some mental retardation and other complications of the disease. For this reason, some states screen for homocystinuria in all newborns.

Patients with persistent rises in blood homocysteine levels are at increased risk for blood clots. Clots can cause significant medical problems and shorten lifespan.

Complications

Most serious complications result from blood clots. These episodes can be life threatening.

Dislocated lenses of the eyes can severely impair vision. Lens replacement surgery should be considered.

Mental retardation is a serious consequence of the disease. However, it can be lessened if diagnosed early.

Calling your health care provider

Call your health care provider if you or a family member shows symptoms of this disorder, particularly if there is a family history of homocystinuria. Also call if you have a family history and are planning to have children.

Prevention

Genetic counseling is recommended for prospective parents with a family history of homocystinuria. Intrauterine diagnosis of homocystinuria is available. This involves culturing amniotic cells or chorionic villi to test for cystathionine synthase (the enzyme that is missing in homocystinuria).

References

Rezvani I. Defects in metabolism of amino acids. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 85.