pediatrics
Methionine Metabolism Disorders
Classic homocystinuria
This disorder is caused by an Autosomal Recessive deficiency of cystathionine beta-synthase, which catalyzes cystathionine formation from homocysteine and serine. Homocysteine accumulates and dimerizes to form the disulfide homocystine, which is excreted in the urine. Because remethylation is intact, some of the additional homocysteine is converted to methionine, which accumulates in the blood. Excess homocysteine predisposes to thrombosis and has adverse effects on connective tissue (perhaps involving fibrillin), particularly the eyes and skeleton; adverse neurologic effects may be due to thrombosis or a direct effect. Arterial and venous thromboembolic phenomena can occur at any age. Many patients develop ectopia lentis (lens subluxation), intellectual disability, and osteoporosis. Patients can have a Marfan Syndrome even though they are not usually tall. Diagnosis of classic homocystinuria is by Screening Tests for Newborns for elevated serum methionine; elevated total plasma homocysteine levels and/or DNA testing are confirmatory. Enzymatic assay in skin fibroblasts can also be done. Treatment of Classic homocystinuria is a low-methionine diet and L- 