CBS deficiency

= CBS Deficiency = CBS Deficiency, also known as Cystathionine Beta-Synthase Deficiency, is a rare genetic disorder that affects the metabolism of the amino acid homocysteine. It is classified as a type of homocystinuria, which is characterized by an abnormal accumulation of homocysteine in the blood and urine.

Pathophysiology

CBS deficiency is caused by mutations in the CBS gene located on chromosome 21. This gene encodes the enzyme cystathionine beta-synthase, which is crucial for the conversion of homocysteine to cystathionine in the transsulfuration pathway. When this enzyme is deficient or dysfunctional, homocysteine accumulates, leading to various clinical manifestations.

Clinical Features

Individuals with CBS deficiency may present with a wide range of symptoms, including:

• Developmental delay and intellectual disability
• Skeletal abnormalities such as osteoporosis and scoliosis
• Ectopia lentis, which is the displacement of the eye lens
• Thromboembolic events due to increased blood clotting
• Vascular complications, including atherosclerosis

Diagnosis

Diagnosis of CBS deficiency is typically made through:

• Measurement of elevated homocysteine levels in the blood and urine
• Genetic testing to identify mutations in the CBS gene
• Enzyme assay to assess the activity of cystathionine beta-synthase

Treatment

Management of CBS deficiency involves:

• Dietary restriction of methionine, an amino acid that is a precursor to homocysteine
• Supplementation with vitamin B6, vitamin B12, and folate to enhance residual enzyme activity and promote alternative metabolic pathways
• Betaine supplementation to lower homocysteine levels
• Regular monitoring and management of complications such as thrombosis and osteoporosis

Prognosis

With early diagnosis and appropriate treatment, individuals with CBS deficiency can lead relatively normal lives. However, untreated or poorly managed cases can result in significant morbidity and mortality due to cardiovascular and neurological complications.

Research and Future Directions

Ongoing research aims to better understand the genetic and biochemical basis of CBS deficiency and to develop novel therapeutic approaches, including enzyme replacement therapy and gene therapy.

See Also

• Homocystinuria
• Metabolic disorders
• Genetic testing

External Links

• National Organization for Rare Disorders
• Genetics Home Reference

NIH genetic and rare disease info

• NIH info on CBS deficiency

CBS deficiency is a rare disease.