Homocystinuria, Diagnosis and Treatment
- 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.
Definition of Homocystinuria
It is characterized by increased plasma concentration of methionine, free homocysteine, and cysteine-homocysteine disulfide together with low cystine.
Pathophysiology of Homocystinuria
- 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 the cystathionine beta-synthase enzyme deficiency.
- This is a metabolic disorder resulting from a deficiency in the 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 of Homocystinuria
- Clinical presentation may be nonspecific, and there is failure to thrive and development is delayed.
- Diagnosis is usually delayed up to 3 years of age if the newborn screening is not done.
- Untreated patients are associated with:
- Dislocated lenses, myopia, glaucoma, retinal detachment, and degeneration.
- Optic atrophy and cataract may develop later on.
- Muscle weakness.
- Osteoporosis is quite common.
- Arterial and venous thrombosis.
- Delay in the development of the infants.
- Mental retardation is seen in >50% of the cases.
- These neurological symptoms include seizures, abnormal EEG, and psychiatric abnormalities.
- Thromboembolic attacks are common.
- 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.
- Spidery fingers (arachnodactyly).
- Tall, thin build.
- The amino acid screen of blood and urine.
- Methionine is tested in the 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 of Homocystinuria
- Random urine samples are negative.
- Methionine level = 1.0 to 2.0 mg/dL (67 to 134 µmol/L).
- No specific treatment.
- Dietary restriction of the methionine.
- The patients are given high doses of Vit. B6.
- 50% may respond and will need it. B6 for the rest of life.
- In unresponsive patients given a 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.