Homocystinuria is an inherited disorder involving the metabolism of the amino acid methionine.
Causes, incidence, and risk factors
Homocystinuria is inherited as an autosomal recessive trait. Usual findings in homocystinuria are myopia ( nearsightedness ), dislocation of the lens of the eye, and a tendency to develop venous and arterial clots ( thrombi ). Newborn infants appear normal, and early symptoms, if present at all, are vague and may occur as mildly delayed development or failure to thrive . Increasing visual problems may lead to diagnosis of this condition when the child, on examination, is discovered to have dislocated lenses and myopia. Some degree of mental retardation is usually seen, but some affected people have normal IQs. When mental retardation is present, it is generally progressive if left untreated. Psychiatric disease can also result. Homocystinuria has several features in common with Marfan syndrome including dislocation of the lens, a tall, thin build with long limbs; spidery fingers ( arachnodactyly ); and a pectus deformity of the chest. In addition, affected people may have high arches of the feet ( pes cavus ), knock-knees ( genu valgum ), and a curved spine ( scoliosis ). Affected people commonly develop blood clots . These blood clots can dislodge (embolus) and the resulting thromboembolic episodes can cause damage in any tissue the embolus lodges in. Emboli to the brain can produce severe sequela such as stroke.
Signs and tests
During physical examination of the child, the health care provider may notice a tall, thin (Marfanoid) stature with pectus deformity of the chest or scoliosis. If there is poor or double vision, an ophthalmologist should perform a dilated eye exam where dislocation of the lens of the eye or myopia may be observed. There may be a history of frequent thromboembolic episodes. Mental retardation, slightly low IQ or psychiatric disease are common. Tests:
A skeletal X-ray shows osteoporosis.
A standard ophthalmic exam confirms myopia and dislocated lens. Affected children may also have cataracts , glaucoma , and retinal detachment .
An amino acid screen of blood and urine shows elevated methionine and homocysteine levels. A liver biopsy and enzyme assay shows an absence of the enzyme cystathionine beta synthase.
A skin biopsy with a fibroblast culture shows an absence of cystathionine beta synthase.
Treatment
There is no specific cure for homocystinuria. However, many people respond to high doses of vitamin B6 (also known as pyridoxine). Slightly less than 50% respond to this treatment; those that do respond need supplemental vitamin B6 for the rest of their lives. A normal dose folic acid supplement is helpful. Those that do not respond require a low methionine diet, and occasionally treatment with trimethylglycine (a medication).
Expectations (prognosis)
Although no specific cure exists for homocystinuria, approximately half of the affected people can be helped by vitamin B6 therapy. If the diagnosis is made while a patient is young, a low methionine diet started promptly and strictly adhered to can spare some mental retardation and other complications of the disease. For this reason, some states screen for homocystinuria in all newborns.
Complications
Most serious complications result from blood clots , and these episodes can be life threatening. Dislocated lens(es) of the eyes can severely impair vision and lens replacement surgery should be considered. Mental retardation is a serious consequence of the disease which can be moderated if diagnosed early.
Calling your health care provider
Call your health care provider if you or a family member shows signs and symptoms, or if there is a family history of homocystinuria.
Prevention
Genetic counseling is recommended for prospective parents with a family history of homocystinuria. Intrauterine diagnosis of homocystinuria is available and is made by culturing amniotic cells or chorionic villi in order to test the presence or absence of cystathionine synthase (the enzyme that is missing in homocystinuria).