How common is homocystinuria and how is it diagnosed?
Cystathionine β-synthase deficiency occurs in approximately 1 in 200,000 (or less) live births in the United States, prompting some states to require newborn homocysteine screening. It is thought that heterozygotes for cystathionine β-synthase deficiency (1 in 70 in the general population) are unaffected but may be at risk for premature peripheral and cerebral vascular disease.
In the classic form of homocystinuria due to cystathionine β-synthase deficiency (homocystinuria I), homocysteine and methionine are increased in the blood and urine. The urinary cyanide nitroprusside test detects sulfhydryl-containing amino acids in urine and is typically used as a screening test but is not specific for a particular enzymatic defect.
Patients with homocystinuria due to a metabolic defect that affects the conversion of homocysteine to methionine ; methionine synthase deficiency [homocystinuria II] or a deficiency of MTHFR [homocystinuria III]) have a different metabolic pattern with low normal (not high) levels of plasma methionine. Notably, patients with vitamin B 12 or folate deficiency can also have high levels of plasma and urinary homocysteine, but low normal levels of plasma methionine. These patients can develop premature vascular disease, but not the other manifestations of homocystinuria.
Therefore, a combination of homocysteine and methionine levels in plasma and urine must be measured to make an accurate diagnosis. Precise tissue (e.g., cultured skin fibroblasts) enzyme assays can also be performed to assess the activity of cystathionine β-synthase and its responsiveness to pyridoxal phosphate (vitamin B 6 ).
