Cystathionine beta synthetase deficiency

Cystathionine beta-synthase deficiency is a rare, inherited metabolic disorder characterized by the absence or malfunctioning of the enzyme cystathionine beta-synthase (CBS). This enzyme plays a crucial role in the methionine metabolism pathway, specifically in the conversion of homocysteine to cystathionine. The deficiency leads to an accumulation of homocysteine in the blood and urine, a condition known as homocystinuria. Homocystinuria due to CBS deficiency can have significant impacts on the nervous system, skeletal system, eyes, and cardiovascular system.

Symptoms and Signs

The symptoms of cystathionine beta-synthase deficiency can vary widely among affected individuals. Common manifestations include:

• Intellectual disability or developmental delay
• Ectopia lentis (dislocation of the lens of the eye)
• Myopia (nearsightedness)
• Skeletal abnormalities such as osteoporosis, tall stature, and a Marfanoid habitus
• Thromboembolism (blood clots that can lead to stroke or pulmonary embolism)
• Atherosclerosis at an early age

Causes

Cystathionine beta-synthase deficiency is caused by mutations in the CBS gene, which provides instructions for making the enzyme cystathionine beta-synthase. These mutations lead to reduced activity or complete absence of the enzyme, disrupting the normal metabolism of methionine and leading to elevated levels of homocysteine.

Diagnosis

Diagnosis of cystathionine beta-synthase deficiency involves a combination of clinical evaluation, family history, and laboratory tests. Elevated levels of homocysteine in the blood and urine are indicative of the disorder. Genetic testing can confirm the diagnosis by identifying mutations in the CBS gene.

Treatment

Treatment for cystathionine beta-synthase deficiency focuses on reducing homocysteine levels and managing symptoms. Options include:

• Dietary restrictions to limit methionine intake
• Supplementation with vitamin B6 (pyridoxine), which can help lower homocysteine levels in some affected individuals
• Administration of betaine, which helps in the remethylation of homocysteine to methionine
• Use of anticoagulants to prevent thromboembolic events

Prognosis

The prognosis for individuals with cystathionine beta-synthase deficiency varies depending on the severity of the enzyme deficiency, the age at diagnosis, and the effectiveness of treatment. Early diagnosis and treatment can significantly improve the quality of life and reduce the risk of complications.