0521779407-09 CUNY1086/Karliner 0 521 77940 7 June 4, 2007 21:13
724 Homocystinuriadifferential diagnosis
■Marfan syndrome (normal homocystine levels, aortic root dilatation,
lens dislocation usually upwards)
■other causes of homocystinuria: 5,10-methylene tetrahydrofolate
reductase (MTHFR) deficiency (normal or decreased serum methio-
nine), functional methionine synthetase deficiency (cobalamin G
or E disease) – diagnosed by fibroblast complementation analysis,
functional combined methylmalonyl-CoA mutase/methionine syn-
thetase deficiency (cobalamin C, D, or F disease) – these disorders
also have elevated blood and urine methylmalonic acid, diagnosed
by fibroblast complementation analysis
management
What to Do First
■trial of vitamin B6 (pyridoxine); treat concomitantly with folate
■assess severity of eye, vascular, bone disease
General Measures
■referral to biochemical genetics specialist center
■avoid folate/vitamin B12 deficiency
specific therapy
■indicated for all patients for life
■Treatment options
■pyridoxine titrated to individual response in vitamin B6-responsive
patients
■low methionine diet in vitamin B6-unresponsive patients (may not
be tolerated by many patients diagnosed after infancy)
■supplement with vitamins (esp. folate and vitamin B12), minerals,
trace elements
■betaine may decrease homocystine in vitamin B6-unresponsive
patients
■consider use of platelet function inhibitors and/or aspirin to
decrease risk of thromboembolism
Side Effects & Complications
■large doses of vitamin B6 (>500 mg/day) may cause peripheral neu-
ropathy with ataxia
follow-up
During Treatment
■monitor blood methionine, total homocyst(e)ine, urine homocys-
tine to assess vitamin B6 responsiveness