Prevalence |
1:144,000 (UK data – pyridoxine unresponsive) |
Defect type |
The most common cause of homocystinuria is a defect in the enzyme β-cystathionine synthase (CBS); this is referred to as "classical" homocystinuria. This occurs as a pyridoxine responsive and pyridoxine unresponsive form.
The mode of inheritance of classical homocystinuria is autosomal recessive. |
Typical age at clinical diagnosis |
6 months - adult (UK data), usually around 2-3 years |
Clinical Effects:
- Babies do not have any problems at birth and, without screening, HCU is not usually diagnosed until 2-3 years of age.
- Classical homocystinuria is associated with a number of problems.
These can include:
- Severe short-sightedness (Myopia)
- Dislocation of the lens of the eye
- Learning difficulties
Osteoporosis (a condition which increases the likelihood of breaking the bones)
- Lengthening of the long bones
- Blood clots, which can affect the legs (DVTs) or cause strokes
- Without treatment, around a quarter of patients will die before the age of 30, usually as a result of a blood clot.
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Treatment:
In some children with HCU, the level of homocysteine can be controlled by giving Vitamin B6 (Pyridoxine). Children who do not respond to vitamin B6 are treated with a low protein diet; these children also need a special amino acid mixture that does not produce homocysteine. They may also be given folic acid, vitamin B12 and a medicine called betaine.
Effectiveness of treatment:
Most problems are prevented if treatment is started during infancy. If started later, treatment is likely to prevent new problems from developing and it may improve existing problems.
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Positive predictive value |
36% (UK data) |
Sensitivity |
Approx 100% |
Screening index metabolite |
Methionine |
Confirmatory test |
Plasma aminoacids and total plasma homocysteine |
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