HCU Fact File

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.


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.     


Positive predictive value 36% (UK data)
Sensitivity Approx 100%
Screening index metabolite Methionine
Confirmatory test Plasma aminoacids and total plasma homocysteine