Homocystinuria

Definition

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

Alternative Names

Cystathionine beta synthase deficiency

Causes

Homocystinuria is inherited in families as an autosomal recessive trait. This means that the child must inherit the non-working 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
• Intellectual disability
• Knock knees
• Long limbs
• Mental disorders 
• Nearsightedness
• Spidery fingers (arachnodactyly)
• Tall, thin build

Exams and Tests

The health care provider may notice that the child is tall and thin (Marfanoid).

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 blood clots. Intellectual disability, slightly low IQ, or mental illness 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, just under half of people respond to high doses of vitamin B6 (also known as pyridoxine).

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

Neither a low-methionine diet nor medication will improve existing intellectual disability. Medication and diet should be closely supervised by a physician who has experience treating homocystinuria.

Taking a folic acid supplement and adding cysteine (an amino acid) to the diet are helpful.

Outlook (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 intellectual disability and other complications of the disease. For this reason, some states screen for homocystinuria in all newborns.

Patients whose blood homocysteine levels continue to rise are at increased risk for blood clots. Clots can cause serious medical problems and shorten lifespan.

Possible Complications

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

Dislocated lenses of the eyes can seriously damage vision. Lens replacement surgery should be considered.

Intellectual disability is a serious consequence of the disease. However, it can be reduced if diagnosed early.

When to Contact a Medical Professional

Call your health care provider if you or a family member shows symptoms of this disorder, especially if you have 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 people with a family history of homocystinuria who want to have children. 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).

If there are known gene mutations in the parents or family, samples from chorionic villus sampling or amniocentesis can be used to test for these mutations.

References

Rezvani I, Melvin JJ. Defects in metabolism of amino acids. In: Kliegman RM, Stanton BF, St. Geme J, Schor N, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 79.

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