Homocysteinuria
From Iusmgenetics
(Difference between revisions)
(Created page with '==Homocysteinuria== ===General background information=== *This disease surrounds the biochemistry of converting methionine to homocystein to cystathionnine to cysteine. **Any de…') |
|||
| Line 18: | Line 18: | ||
**Cobalamin absorption defects | **Cobalamin absorption defects | ||
**Cobalamin transport defects | **Cobalamin transport defects | ||
| + | *Don't worry about all those other defects, we'll worry about the cystathionine synthase (because that one we can treat) | ||
*http://www.healthline.com/images/gale/big/gegd_0002_0001_0_img0115.jpg | *http://www.healthline.com/images/gale/big/gegd_0002_0001_0_img0115.jpg | ||
===Etiology=== | ===Etiology=== | ||
| + | *Homocysteine is the toxic substance that causes disease. | ||
| + | *Homocystein may impair disulphide bridges in FBN1 and thus cause a Marfan-like disorder (because of defective fibrillin). | ||
===Pathogenesis=== | ===Pathogenesis=== | ||
| Line 27: | Line 30: | ||
*Like Marfans, three systems involved: skeletal, ocular, vascular: | *Like Marfans, three systems involved: skeletal, ocular, vascular: | ||
**Long, thin bones | **Long, thin bones | ||
| - | **Lens dislocation | + | **Lens dislocation '''(Marfan dislocates upward, homocystinuria dislocates downward)''' |
**Thromboembolism | **Thromboembolism | ||
***With potential for mental impairment secondary to embolism | ***With potential for mental impairment secondary to embolism | ||
| Line 35: | Line 38: | ||
===Treatment=== | ===Treatment=== | ||
*Because cystathionine beta synthase requires pyridoxine (B6) as a cofactor, we often provide B6 supplements to boost the function of endogenous (albeit damaged) CBS. | *Because cystathionine beta synthase requires pyridoxine (B6) as a cofactor, we often provide B6 supplements to boost the function of endogenous (albeit damaged) CBS. | ||
| + | *Cystathionine beta synthase also requires pyridoxal phosphate as a cofactor. | ||
===Recent research=== | ===Recent research=== | ||
Revision as of 02:46, 14 October 2011
Contents |
Homocysteinuria
General background information
- This disease surrounds the biochemistry of converting methionine to homocystein to cystathionnine to cysteine.
- Any defect in this pathway (which requires methionine, folate, cobalamin, and pyrodoxine) can cause homocysteinuria.
Mode of inheritance
- Autosomal recessive
Single important gene
- CBS: Cystathionine beta synthase defect is the classic case.
- There is locus heterogeneity in homocysteinuria as there are other loci that can cause the disease upon damage.
- There are 5 other known defects that can cause homocysteinuria.
- Methylene-H4-folate reductase defects
- Cytosolic cobalamin metabolism defects
- Methylcobalamin synthesis defects
- Cobalamin absorption defects
- Cobalamin transport defects
- Don't worry about all those other defects, we'll worry about the cystathionine synthase (because that one we can treat)
Etiology
- Homocysteine is the toxic substance that causes disease.
- Homocystein may impair disulphide bridges in FBN1 and thus cause a Marfan-like disorder (because of defective fibrillin).
Pathogenesis
Phenotypic information
- Like Marfans, three systems involved: skeletal, ocular, vascular:
- Long, thin bones
- Lens dislocation (Marfan dislocates upward, homocystinuria dislocates downward)
- Thromboembolism
- With potential for mental impairment secondary to embolism
Diagnosis
Treatment
- Because cystathionine beta synthase requires pyridoxine (B6) as a cofactor, we often provide B6 supplements to boost the function of endogenous (albeit damaged) CBS.
- Cystathionine beta synthase also requires pyridoxal phosphate as a cofactor.
Recent research
5 important facts
Not to be confused with
- Marfan syndrome
- Both present with similar skeletal, ocular, and vascular symptoms.
- Excess homocysteine may inhibit the appropriate disulfide briding in FBN1 and thus cause Marfan-like symptoms, thus reducing the amount of functional fibrillin-1.
- Recall that FBN1 is important for TGF-beta signaling and therefore ECM maintenance.
