wiki pageCreated: 2026-04-02T07:20:13By: crosslink-migrationQuality:
50%✓ SciDEXID: wiki-diseases-homocystinuria
📖 Wiki Page
disease815 wordssynced 2026-04-02
Homocystinuria
Overview
Homocystinuria, more precisely termed classical homocystinuria or cystathionine beta-synthase (CBS) deficiency, is a rare autosomal recessive metabolic disorder characterized by elevated levels of homocysteine in the blood and urine. This condition results from deficient activity of the enzyme cystathionine beta-synthase, which is essential for the transsulfuration pathway of methionine metabolism[@mudd1985]. The disease has significant neurological manifestations and represents one of the most common inherited causes of hyperhomocysteinemia.
Genetics
Classical homocystinuria is caused by mutations in the CBS gene (cystathionine beta-synthase) located on chromosome 21q22.3. Over 200 pathogenic variants have been identified, with certain mutations being prevalent in specific populations:
Common Mutations
p.I278T — common in European populations
p.G307S — prevalent in Irish ancestry
p.A114V — found in various populations
p.R125Q — observed in multiple ethnic groups
Inheritance Pattern
Autosomal recessive inheritance
Both copies of the CBS gene must be mutated for disease expression
Carrier parents have a 25% chance of having an affected child
Approximately 1 in 200,000-300,000 births worldwide
Biochemistry and Pathophysiology
Normal Methionine Metabolism
The methionine cycle involves:
Methionine → S-adenosylmethionine (SAM)
SAM → S-adenosylhomocysteine (SAH)
SAH → Homocysteine
Homocysteine → Methionine (via remethylation) OR → Cystathionine (via transsulfuration)
...
Homocystinuria
Overview
Homocystinuria, more precisely termed classical homocystinuria or cystathionine beta-synthase (CBS) deficiency, is a rare autosomal recessive metabolic disorder characterized by elevated levels of homocysteine in the blood and urine. This condition results from deficient activity of the enzyme cystathionine beta-synthase, which is essential for the transsulfuration pathway of methionine metabolism[@mudd1985]. The disease has significant neurological manifestations and represents one of the most common inherited causes of hyperhomocysteinemia.
Genetics
Classical homocystinuria is caused by mutations in the CBS gene (cystathionine beta-synthase) located on chromosome 21q22.3. Over 200 pathogenic variants have been identified, with certain mutations being prevalent in specific populations:
Common Mutations
p.I278T — common in European populations
p.G307S — prevalent in Irish ancestry
p.A114V — found in various populations
p.R125Q — observed in multiple ethnic groups
Inheritance Pattern
Autosomal recessive inheritance
Both copies of the CBS gene must be mutated for disease expression
Carrier parents have a 25% chance of having an affected child
Approximately 1 in 200,000-300,000 births worldwide
Biochemistry and Pathophysiology
Normal Methionine Metabolism
The methionine cycle involves:
Methionine → S-adenosylmethionine (SAM)
SAM → S-adenosylhomocysteine (SAH)
SAH → Homocysteine
Homocysteine → Methionine (via remethylation) OR → Cystathionine (via transsulfuration)
Enzyme Deficiency
CBS deficiency disrupts the transsulfuration pathway, leading to:
Accumulation of homocysteine — toxic to vascular endothelium and [neurons](/entities/neurons)
Accumulation of methionine — due to impaired conversion to cystathionine
Reduced cysteine production — affecting glutathione synthesis
Impaired methylation reactions — due to elevated SAH