Alkaptonuria: Causes, Symptoms, and Treatment
Medically reviewed by Achuta Uppu, MD, Internal Medicine. Last reviewed: October 23, 2026.
What kind of doctor treats Alkaptonuria?
A geneticist, a doctor who treats inherited conditions, and a rheumatologist, a doctor who treats joint disease, usually treat alkaptonuria. An orthopedic surgeon, a bone and joint surgeon, may do joint replacement if joints wear out. A direct primary care or concierge doctor can be a first stop for an evaluation and can refer you to a specialist when needed.
What is alkaptonuria?
Alkaptonuria is a rare inherited condition. The body cannot fully break down two amino acids, which are the building blocks of proteins. These amino acids are tyrosine and phenylalanine. A substance called homogentisic acid builds up in the body. It turns urine dark when the urine meets the air. Over time it darkens cartilage and other tissues. This is called ochronosis, a buildup of dark blue-black pigment in the body's tissues. Alkaptonuria affects 1 in 250,000 to 1 million people in the United States.
Symptoms
Urine may turn dark brown or black when it is exposed to air. This can happen in a baby's diaper. Many people do not find out they have the condition until mid-adulthood, around age 40, when joint problems start. Other signs include:
- Darkening of the outer ear.
- Dark spots on the white of the eye and on the cornea, the clear front of the eye.
- Arthritis in the spine and large joints such as the hips and knees. It usually gets worse over time.
- Back pain when the discs between the bones of the spine harden.
The pigment can also build up on the heart valves, most often the mitral valve. The valves can narrow and leak, and some people need valve replacement. Kidney stones and prostate stones may be more common. Removing large amounts of pigment can strain the kidneys, and this can lead to kidney failure over time.
Causes and who gets it
A change in the HGD gene causes alkaptonuria. This gene gives the instructions for making an enzyme called homogentisate 1,2-dioxygenase. This enzyme helps break down tyrosine and phenylalanine. When it does not work well, homogentisic acid builds up in tissues and urine.
Alkaptonuria is inherited in an autosomal recessive pattern. A child must get a changed copy of the gene from both parents. Parents who carry one changed copy usually have no symptoms. If both parents carry a change, each child has a 1 in 4 chance of having the condition. It is more common in parts of Slovakia and in the Dominican Republic.
How doctors diagnose it
Doctors do a urine test. If ferric chloride, a chemical, is added to the urine, the urine turns black in people with this condition. A blood test can show whether you carry a non-working copy of the gene that causes alkaptonuria.
Treatment
In June 2025 the FDA approved a medicine called nitisinone (brand name Harliku) for adults with alkaptonuria. It is the first treatment that changes how the disease progresses. As a pill taken once a day, it lowers homogentisic acid in the urine by more than 95%. The medicine can raise tyrosine levels in the blood, and this can cause eye and skin problems. People who take it need blood tests and eye checks. They also follow a diet low in tyrosine and phenylalanine, guided by a dietitian. Nitisinone cannot undo damage that has already built up.
For joint pain, doctors may recommend anti-inflammatory medicines such as NSAIDs, pain relievers like ibuprofen, and physical therapy. A low-protein diet may help some people, but many find it hard to follow. People with severe joint damage may need joint replacement surgery. With appropriate medical management, people with alkaptonuria generally have a normal life expectancy.
When to see a doctor
Call your doctor right away if your own urine or your child's urine becomes dark brown or black when it is exposed to air. Call 911 or go to the emergency room right away if you have chest pain or discomfort lasting two minutes or more, or trouble breathing. If alkaptonuria runs in your family and you plan to have children, talk with a doctor about genetic counseling. A blood test can show whether you carry the changed gene.
How a direct primary care or concierge doctor fits in
A direct primary care doctor charges a flat monthly fee instead of billing insurance, while a concierge doctor usually charges more and often works alongside insurance. Your doctor can check your urine and blood and track your joints and heart over time. They can also coordinate your care with a geneticist and a rheumatologist.
Common questions
Does nitisinone cure alkaptonuria?
No. It lowers homogentisic acid in the urine by more than 95% and changes how the disease progresses, but it cannot undo damage that has already built up.
How do people get alkaptonuria?
It is inherited in an autosomal recessive pattern. A child must get a changed copy of the HGD gene from both parents. Parents who carry one changed copy usually have no symptoms.
When do symptoms usually start?
Urine can darken in a baby's diaper. But many people do not find out they have the condition until mid-adulthood, around age 40, when joint problems start.
What is ochronosis?
Ochronosis is a buildup of dark blue-black pigment in tissues such as the joints, tendons, and ligaments. The pigment can be seen in the whites of the eyes, the outer ears, and the hands.
Sources
- MedlinePlus Genetics - Alkaptonuria
- MedlinePlus Medical Encyclopedia - Alkaptonuria
- Annals of Medicine and Surgery - Harliku (nitisinone): first FDA-approved disease-modifying therapy for alkaptonuria
Medical Disclaimer
This content is for general educational and informational purposes only and is not medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment, and reading it does not create a doctor-patient relationship. Always seek the advice of your physician or another qualified health provider with any questions about a medical condition, and never disregard or delay seeking professional advice because of something you read here. If you think you may have a medical emergency, call 911 (or your local emergency number) immediately.
