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# Homocystinuria

In homocystinuria homocysteine builds up: the lens dislocates, bones become long and fragile, and thromboses appear.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Lens](https://durgical.com/en/anatomy/lens/)
- [Zonular fibres](https://durgical.com/en/anatomy/ciliary-zonule/)
- [Internal carotid artery](https://durgical.com/en/anatomy/internal-carotid-artery/)
- [Superior sagittal sinus](https://durgical.com/en/anatomy/superior-sagittal-sinus/)
- [Femoral vein](https://durgical.com/en/anatomy/femoral-vein/)

## In biochemistry

- [Methionine cycle and transsulfuration: Exit · Cystathionine β-synthase (CBS)](https://durgical.com/en/biochemistry/pathways/methionine-cycle-and-transsulfuration/#paso-5)
- [Homocysteine](https://durgical.com/en/biochemistry/molecules/homocysteine/)
- [S-adenosylmethionine (SAM)](https://durgical.com/en/biochemistry/molecules/s-adenosylmethionine/)
- [Cystathionine β-synthase (CBS)](https://durgical.com/en/biochemistry/enzymes/cystathionine-synthase/)
- [Methionine synthase](https://durgical.com/en/biochemistry/enzymes/methionine-synthase/)
- [One-carbon metabolism (folate, B12 and SAM)](https://durgical.com/en/biochemistry/topics/one-carbon-metabolism/)
- [Methionine](https://durgical.com/en/biochemistry/molecules/methionine/)
- [S-Adenosylhomocysteine (SAH)](https://durgical.com/en/biochemistry/molecules/s-adenosylhomocysteine/)

## 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](https://durgical.com/en/anatomy/ciliary-zonule/), 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

## Red flags

- Venous thrombosis or stroke in a child or young adult
- Lens dislocation in a marfanoid patient
- Surgery or immobilisation in a known patient

## 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](https://durgical.com/en/anatomy/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).

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## Related conditions

- [Methylmalonic acidaemia](https://durgical.com/en/conditions/methylmalonic-acidaemia/)
- [Deep vein thrombosis](https://durgical.com/en/conditions/deep-vein-thrombosis/)
- [Ischaemic stroke](https://durgical.com/en/conditions/ischaemic-stroke/)
- [Pulmonary embolism](https://durgical.com/en/conditions/pulmonary-embolism/)
- [Osteoporosis](https://durgical.com/en/conditions/osteoporosis/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Homocystinuria: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/homocystinuria/) (MedlinePlus, US National Library of Medicine, 2026); [CBS gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/cbs/) (MedlinePlus, US National Library of Medicine, 2026); [Homocysteine Test: MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/homocysteine-test/) (MedlinePlus, US National Library of Medicine, 2026).

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Source: https://durgical.com/en/conditions/homocystinuria/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/homocystinuria/