homocystinuria

Homocystinuria is a group of inherited disorders characterized by high levels of homocysteine in blood and urine due to defects in methionine metabolism. The most common form is cystathionine beta-synthase (CBS) deficiency, which causes accumulation of homocysteine and methionine. Other forms result from defects in remethylation of homocysteine to methionine, such as methionine synthase or MTHFR deficiency, or impaired cobalamin processing. All forms are typically autosomal recessive.

Clinical features include marfanoid habitus, lens dislocation (ectopia lentis), skeletal abnormalities, osteoporosis, developmental delay, and a high risk of thrombosis, often at a young age. The presentation varies depending on the defect and treatment.

Diagnosis: Elevated plasma homocysteine is the hallmark. The pattern of methionine helps distinguish CBS deficiency (often high methionine) from remethylation defects (low or normal methionine). Urine homocystine and amino acid analyses, plus genetic testing of CBS and other relevant genes, confirm the diagnosis. Newborn screening detects some forms.

Treatment aims to lower homocysteine and prevent complications. Some individuals with CBS deficiency respond to pyridoxine (vitamin B6). Other strategies include a low-methionine diet with cysteine supplementation, betaine to remethylate homocysteine, and folate and vitamin B12 as needed. Anticoagulation may be used to manage thrombotic risk. Regular monitoring of homocysteine levels guides therapy.

Prognosis improves with early diagnosis and ongoing treatment, though vascular complications remain a risk. With appropriate management, many patients achieve good outcomes.