Homocystinuria is a rare autosomal recessive condition, occurring in approximately 1 in 100,000 births. The classic form is usually caused by mutations in the gene encoding cystathionine β-synthase, which causes homocysteine to accumulate in the plasma and to be excreted in the urine.
Figure 23-10 Lens subluxation in a patient with Marfan syndrome.
(Courtesy of Gregg T. Lueder, MD.)
The clinical manifestations of homocystinuria vary; the eye, skeletal system, central nervous system, and vascular system can be affected. Most of the abnormalities develop after birth and become progressively worse with age. The ophthalmologist may see patients with this disorder before the systemic diagnosis is made. The skeletal features are similar to those of Marfan syndrome. Affected patients are usually tall and have osteoporosis, scoliosis, and chest deformities. Central nervous system abnormalities occur in approximately 50% of patients; intellectual disability and seizures are the most common.
Vascular complications are common and secondary to thrombotic disease, which affects large or medium-sized arteries and veins anywhere in the body. Hypertension and cardiomegaly are also common. Anesthesia carries a higher risk for patients with homocystinuria because of thromboembolic phenomena; thus, this disorder should be identified before patients undergo general anesthesia.
The main ocular finding is lens subluxation, most frequently inferiorly, but the direction of subluxation is not diagnostic. Subluxation typically begins between the ages of 3 and 10 years. The lenses may dislocate into the anterior chamber, a finding suggestive of homocystinuria (Fig 23-11). The zonular fibers are frequently broken, in contrast with those in Marfan syndrome.
The diagnosis is confirmed by the detection of disulfides, including homocystine, in the urine. Medical management of homocystinuria is directed toward normalizing the biochemical abnormality. Dietary management (low-methionine diet and supplemental cysteine) may be attempted. Supplementation with the coenzyme pyridoxine (vitamin B6) diminishes systemic problems in approximately 50% of cases.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.