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# Alkaptonuria

In alkaptonuria homogentisic acid builds up: urine darkens in air and, over the years, cartilage and joints become stained and worn.

Updated 2026-11-01

## Structures involved

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

- [L4–L5 disc](https://durgical.com/en/anatomy/l4-l5/)
- [Femoral cartilage](https://durgical.com/en/anatomy/articular-cartilage-of-femur/)
- [L3–L4 disc](https://durgical.com/en/anatomy/l3-l4/)
- [L5–S1 disc](https://durgical.com/en/anatomy/l5-s1/)
- [Tibial cartilage](https://durgical.com/en/anatomy/articular-cartilage-of-tibial-plateau/)
- [Aortic right coronary cusp](https://durgical.com/en/anatomy/right-coronary-leaflet/)
- [Aortic left coronary cusp](https://durgical.com/en/anatomy/left-coronary-leaflet/)
- [Aortic non-coronary cusp](https://durgical.com/en/anatomy/non-coronary-leaflet-of-aortic-valve/)

## In biochemistry

- [Phenylalanine and tyrosine metabolism: Step 4 · Homogentisate 1,2-dioxygenase (homogentisate oxidase, HGD)](https://durgical.com/en/biochemistry/pathways/phenylalanine-and-tyrosine-metabolism/#paso-4)
- [Tyrosine](https://durgical.com/en/biochemistry/molecules/tyrosine/)

## Why it happens

- [Pigments in tissue: lipofuscin, hemosiderin, melanin, bilirubin, carbon](https://durgical.com/en/general-pathology/pigments-in-tissue-lipofuscin-hemosiderin-melanin-bilirubin-carbon/)

## What it is

An inherited disease from lack of homogentisate 1,2-dioxygenase. Homogentisic acid builds up, appears in urine and deposits in connective tissue (ochronosis).

## Who gets it

Rare: between 1 in 250,000 and 1 in a million people in the United States. It is more common in parts of Slovakia and in the Dominican Republic.

## Causes

- Variants in both alleles of the HGD gene (autosomal recessive)

## Risk factors

- Carrier parents
- Consanguinity

## Pathophysiology

In tyrosine breakdown, homogentisate is not opened. It builds up and oxidises to a melanin-like pigment that binds collagen. Stained cartilage becomes stiff and breaks up: arthropathy of the spine and large joints, valve calcification and stones.

## Symptoms and signs

- Urine that darkens in air or nappies stained black
- Grey-blue pigment in the [sclera](https://durgical.com/en/anatomy/sclera/) and ear cartilage (from about age 30)
- Low back pain and spinal stiffness
- Early osteoarthritis of knees, hips and shoulders

## Red flags

- Aortic stenosis murmur in a young adult with ochronosis
- Renal colic (stones)

## Diagnosis

**Clinical**
Dark urine in childhood or early arthropathy with ochronotic pigment.

**Tests**
High urinary homogentisic acid; HGD gene testing.

**Imaging**
[Spine](https://durgical.com/en/anatomy/region/spine/) X-ray: calcified, narrowed discs; echocardiography to assess the aortic valve.

## Treatment

**Medical**
Nitisinone, which blocks an earlier step of the pathway and greatly lowers homogentisic acid

**Rehabilitation**
Physiotherapy and joint pain control

**Surgical**
Joint or aortic valve replacement when damage is advanced

**Lifestyle**
Lower protein intake (tyrosine and phenylalanine), especially when nitisinone is used

## Complications

- Ochronotic arthropathy of spine and large joints
- Aortic stenosis
- [Kidney](https://durgical.com/en/anatomy/kidney/) and [prostate](https://durgical.com/en/anatomy/prostate/) stones
- Tendon ruptures

## Prognosis

Life expectancy is usually normal, but arthropathy greatly limits mobility from middle age.

## Test yourself

Think of the answer, then tap the question to see it.

## Which enzyme is missing in alkaptonuria?

Homogentisate 1,2-dioxygenase, which opens the ring of homogentisate in tyrosine breakdown.

## What is ochronosis?

Deposition of a dark pigment derived from homogentisic acid in cartilage, tendons, sclera and valves.

## Which drug lowers homogentisic acid?

Nitisinone, which inhibits 4-hydroxyphenylpyruvate dioxygenase, an earlier step of the pathway.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/conditions/alkaptonuria/)

## Related conditions

- [Tyrosinaemia type I (hepatorenal)](https://durgical.com/en/conditions/tyrosinaemia-type-i/)
- [Aortic Valve Stenosis](https://durgical.com/en/conditions/aortic-valve-stenosis/)
- [Knee Osteoarthritis](https://durgical.com/en/conditions/knee-osteoarthritis/)
- [Kidney stones (urolithiasis)](https://durgical.com/en/conditions/kidney-stones/)

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

Sources: [Alkaptonuria: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/alkaptonuria/) (MedlinePlus, US National Library of Medicine, 2026); [HGD gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/hgd/) (MedlinePlus, US National Library of Medicine, 2026); [Tyrosine catabolism](https://reactome.org/PathwayBrowser/#/R-HSA-8963684) (Reactome, 2026).

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