Disease Directory Alkaptonuria
Metabolic

Alkaptonuria

Also known as: AKU, homogentisate dioxygenase deficiency, ochronosis, HGD deficiency

Prevalence

1-9 per 100,000 (Orphanet)

Onset

Adult

Type

Autosomal recessive genetic

Gene

HGD

About Alkaptonuria

Alkaptonuria is a rare inherited disorder of tyrosine metabolism caused by deficiency of homogentisate dioxygenase (HGD), leading to accumulation of homogentisic acid (HGA). Over decades, HGA deposits in connective tissue cause ochronosis — a blue-black pigmentation of cartilage, tendons, and sclerae — and leads to severe early-onset osteoarthritis affecting the spine and large joints. Nitisinone (Orfadin), approved in Europe for AKU, significantly reduces HGA levels.

Common Clinical Features

Dark urine on standing Ochronosis (pigment deposits) Early-onset osteoarthritis Spinal stiffness Aortic stenosis Renal and prostate stones Tendon rupture

Clinical Trial Eligibility Tips

What to know before applying to Alkaptonuria trials.

Nitisinone (NTBC) is approved in Europe — trials may focus on dose optimization, long-term joint outcomes, or combination approaches

Urinary homogentisic acid (HGA) excretion is the primary biomarker — 24-hour urine HGA measurement is standard at screening

Joint disease severity scoring (AKU Society's AKU Severity Score Index) is used as an eligibility and outcome measure

AKU is very rare — contact the DevelopAKUre consortium and AKU Society for trial matching assistance

Patient Resources

Patient Organization

AKU Society

Visit website ↗

Natural History Registry

National Alkaptonuria Centre Registry

Join registry ↗

Orphanet

European reference resource for rare diseases (ORPHA:56)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

Search NORD ↗

Find recruiting Alkaptonuria trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Alkaptonuria. Updated daily.

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