Homocystinuria Flashcards
inheritance pattern
autosomal ressevive disorder
1 in 344000
problem metabolising
methionine causing excess homocystine to be excreted in the urine
homocystine
oxidised form of homocysteine
homocystinurias affects
connective tissue
muscles
CNS
CVS
outline the homocystinuria pathway
- dietary and endogenous protein are sources of methionine
- methionine is converted to homocysteine
- however defect in cystathione B-synthase (most common) means homocysteine is not converted to cystathionine
- cystathione B-synthase requires active form of Vit B6 to act as a co-factor
- cystathionine is converted to cystein
therefore a defect in cystathione B synthase causes an accumulation of
homocysteine
why is homocystine in excess and not homocysteine?
is two homocysteines joined together by a disulphide bond (i.e. the oxidized form of homocysteine). The form of homocysteine that appears in the urine of homocystinuria patients is mostly (~98%) homocystine (hence the name homocystinuria).
elevated plasma homocystein shown to be associated with
CVD
cystine
s two cysteine amino acids bound together by a disulphide bond
homocystinuira vs marfan syndrome
Homocystinuria vs Marfan syndrome
- Marfan syndrome is a genetic disorder of connective tissue.
- Some of the clinical features of homocystinuria, such as lens dislocation and skeletal deformities, are similar in Marfan syndrome
- High levels of homocysteine affect connective tissue and bone (mechanism by which this occurs is not known).
- Excess homocysteine causes damage to collagen and elastic fibres in connective tissue by binding to lysine residues in proteins.
- Metabolites of methionine are toxic to neurones and cause neurological dysfunction
- Symptoms in homocystinuria which are not seen in Marfan syndrome
