Conditions · Metabolism: amino acids and the urea cycle
Homocystinuria !
In homocystinuria homocysteine builds up: the lens dislocates, bones become long and fragile, and thromboses appear.
Updated 2026-11-01
Structures involved
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In biochemistry
- Methionine cycle and transsulfuration: Exit · Cystathionine β-synthase (CBS)
- Homocysteine
- S-adenosylmethionine (SAM)
- Cystathionine β-synthase (CBS)
- Methionine synthase
- One-carbon metabolism (folate, B12 and SAM)
- Methionine
- S-Adenosylhomocysteine (SAH)
What it is
A group of inherited diseases with very high homocysteine in blood and urine. The classic form is due to cystathionine β-synthase (CBS) deficiency.
Who gets it
The classic form affects at least 1 in 200,000 to 335,000 people worldwide; it is more common in Qatar, Norway, Germany and Ireland.
Causes
- Classic: variants of the CBS gene (autosomal recessive)
- Remethylation forms: MTHFR, MTR, MTRR, MMADHC and other B12 defects
Risk factors
- Carrier parents
- Consanguinity
Pathophysiology
Without CBS, homocysteine does not go to cystathionine and cysteine; it builds up and is remethylated to methionine, which also rises. Homocysteine disturbs the cross-links of collagen and of fibrillin in the zonular fibres, damages endothelium and activates clotting. Cysteine becomes essential.
Classification
- Classic, from CBS deficiency (high methionine)
- From remethylation defects (low or normal methionine)
- Pyridoxine (B6) responsive or not
Symptoms and signs
- Downward lens dislocation and high myopia
- Marfanoid habitus: tall stature, long limbs, pectus excavatum
- Early osteoporosis
- Intellectual disability and seizures
- Arterial and venous thrombosis
Diagnosis
- Clinical
- Ectopia lentis with marfanoid habitus or early thrombosis; some countries include it in newborn screening.
- Tests
- Very high plasma total homocysteine; high methionine in the classic form; B12, folate and methylmalonic acid to separate other causes; genetic testing; pyridoxine response trial.
- Imaging
- Bone densitometry for osteoporosis; Doppler ultrasound or angiography if thrombosis is suspected.
Treatment
- Medical
- Pyridoxine (B6) in responders, with folate and B12
- Medical
- Betaine, which remethylates homocysteine to methionine by another route
- Lifestyle
- Low-methionine diet with a cysteine-enriched formula in B6 non-responders
- Surgical
- Surgery for the dislocated lens, with thrombosis prophylaxis
Complications
- Deep vein thrombosis, pulmonary embolism and stroke
- Glaucoma and retinal detachment
- Osteoporotic fractures
- Intellectual disability
Prognosis
Early treatment prevents most complications; thrombosis is the main cause of death without treatment.
Test yourself
Think of the answer, then tap the question to see it.
Which way does the lens dislocate in homocystinuria and in Marfan syndrome?
In homocystinuria it usually dislocates downwards; in Marfan, upwards and outwards.
Which enzyme is missing in classic homocystinuria, and which vitamin does it use?
Cystathionine β-synthase, which uses pyridoxal phosphate (B6).
How is methionine in the classic form and in remethylation defects?
High in the classic form (CBS); low or normal in remethylation defects (MTHFR, B12).
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Homocystinuria: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); CBS gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Homocysteine Test: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026).
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