Homocystinuria

Sample
- This test is done on the urine sample.
- The estimation of methionine can be done on serum as well.
Purpose of the test (Indications)
- To diagnose the complications due to homocystinuria.
Pathophysiology
- In USA 1:150,000 cases may show homocystinuria.
- This is an autosomal recessive disease.
- Homocystinuria is inherited in families as an autosomal recessive trait. This means that the child must inherit the non-working gene from both parents to be seriously affected.
- This is a disorder of methionine metabolism which leads to:
- Accumulation of homocysteine and its metabolites in the blood and urine.
- Normally these are not found in the blood and the urine.
- This may be seen in patients with cobalamin and folate deficiency.
- This is a group of disorders characterized by excessive excretion of homocysteine in the urine.
- Basically, there is a deficiency of cystathionine beta-synthase enzyme deficiency.
- This is a metabolic disorder resulting from a deficiency in cystathionine beta-synthase enzyme which is responsible for the metabolism of methionine and homocysteine.
- In this case, methionine is measured,
- Homocysteine normally does not accumulate in the plasma because it is unstable and when present in excess, undergo oxidation to homocystine.
- The concentration of homocystine in the urine is not detectable but decreased homocysteine conversion to cystathionine by cystathionine beta-synthase enzyme or back to methionine leads to homocystinuria.
- There is an excess of homocysteine and methionine in the blood.
- There is the presence of homocysteine and methionine in the urine.
Clinical presentation
- Untreated patients are associated with :
- Dislocated lenses.
- Cataract.
- Muscle weakness.
- Arterial and venous thrombosis.
- Delay in the development of the infants.
- Hypercoagulability.
- The special dietary supplement may help to prevent this complication.
- Other symptoms seen are :
- Chest deformities (pectus carinatum, pectus excavatum)
- Flushing across the cheeks.
- High arches of the feet.
- Intellectual disability.
- Knock knees.
- Long limbs.
- Mental disorders.
- Nearsightedness.
- Spidery fingers (arachnodactyly).
- Tall, thin build.
Diagnosis
- The amino acid screen of blood and urine
- Genetic testing.
- Liver biopsy and enzyme assay.
- Skeletal x-ray.
- Skin biopsy with a fibroblast culture.
- Standard ophthalmic exam.
- A urine test on cyanide/nitroprusside shows cherry red color.
Normal
- Random urine samples are negative.
- More details can be seen in Homocysteinemia.
Treatment
- No specific treatment.
- The patients are given high doses of Vit.B6.
- 50% may respond and will need vit.B6 for the rest of life.
- In unresponsive patients give low sulfur diet especially low methionine.
- A low dose of folic acid and a supplement of cystine may help.
- Betaine is used to reduce the concentration of homocysteine which will promote the conversion of homocysteine back to methionine.
- A low protein diet is recommended.
- Life expectancy is reduced if not treated.