Homocystinuria due to cystathionine beta-synthase

Homocystinuria due to Cystathionine Beta-Synthase Deficiency

Homocystinuria due to cystathionine beta-synthase deficiency is a rare autosomal recessive metabolic disorder characterized by an accumulation of homocysteine in the blood and urine. This condition is caused by a deficiency in the enzyme cystathionine beta-synthase (CBS), which is crucial for the conversion of homocysteine to cystathionine in the methionine metabolism pathway.

Pathophysiology

Cystathionine beta-synthase is an enzyme that catalyzes the first step in the transsulfuration pathway, converting homocysteine to cystathionine. In individuals with CBS deficiency, this conversion is impaired, leading to elevated levels of homocysteine and methionine in the blood. The accumulation of homocysteine can cause damage to various tissues, particularly affecting the connective tissue, central nervous system, and the cardiovascular system.

Clinical Features

Patients with homocystinuria due to CBS deficiency may present with a variety of symptoms, including:

• Ectopia lentis (dislocation of the lens of the eye)
• Myopia (nearsightedness)
• Osteoporosis
• Marfanoid habitus
• Intellectual disability
• Seizures
• Thromboembolism

The severity and range of symptoms can vary widely among affected individuals.

Diagnosis

Diagnosis of homocystinuria is typically made through a combination of clinical evaluation, biochemical testing, and genetic analysis. Key diagnostic tests include:

• Measurement of plasma homocysteine and methionine levels
• Urinary homocysteine excretion
• Enzyme assay for CBS activity
• Genetic testing for mutations in the CBS gene

Treatment

Management of homocystinuria due to CBS deficiency involves dietary and pharmacological interventions:

• A low-methionine diet supplemented with cystine
• Vitamin B6 (pyridoxine) supplementation, as some patients are responsive to this treatment
• Betaine therapy to help reduce homocysteine levels
• Folic acid and Vitamin B12 supplementation

Regular monitoring of homocysteine levels is essential to adjust treatment and prevent complications.

Prognosis

The prognosis for individuals with homocystinuria due to CBS deficiency varies depending on the severity of the enzyme deficiency and the effectiveness of treatment. Early diagnosis and management can significantly improve outcomes and reduce the risk of complications such as thromboembolic events and progressive neurological damage.

Also see

• Cystathionine beta-synthase
• Methionine metabolism
• Ectopia lentis
• Thromboembolism
• Inborn errors of metabolism