Alkaptonuria
Published on February 20th, 2021. Information will be updated
Alkaptonuria is a sporadic genetic disorder associated with homogentisic acid, an osteotoxin, or renal toxin found in the body. Homogentisic acid can damage the bone and/or joints as well as cause damage to the kidneys. In this case, the homogentisic acid causes damage to the kidneys, which later affects the urine color when exposed to air. Patients with alkaptonuria lack an enzyme called homogentisate dioxygenase, which breaks down this acid. This enzyme is created by a genetic code called HGD in our DNA. Therefore, if mutations were present in the HGD gene, then the homogentisic acid will cause alkaptonuria.
Causes
Since homogentisic acid damages the kidney, this affects the appearance of urine when released from the body. Patients with alkaptonuria may have urine that is darker than usual or even black when exposed to air for a couple of hours which, unfortunately, goes unnoticed. Don’t confuse this with infants having dark urine (that’s when they are dehydrated). Even if the infant is affected with alkaptonuria, it won’t be possible to diagnose it early because this disorder tends to be asymptomatic during the early stages of life. Unlike infancy and childhood, adulthood —specifically after the age of 30— is when symptoms become more noticeable when patients develop discoloration of the tissues in the body, the outer ear, and/or the sclera (the whites of the eye). Keeping in mind the function of homogentisic acid, patients may develop arthritis in large joints, tendonitis, or ankylosis because of the infiltration of osteotoxin in the body.
Risk Factors
Despite the leading cause of alkaptonuria, risk factors such as gender and demographics can increase the symptoms’ development. Although males and females are affected equally, males tend to have their symptoms early, which is more severe. This disorder affects 1 in 250,000- 1,000,000 live births in the United States, making it one of the country’s rarest conditions.
Signs and Symptoms
Note: Article has signs and symptoms in other categories
Diagnosis
Having the symptoms and risk factors in mind, health professionals would be able to diagnose a patient whether he/she is affected with alkaptonuria or not. To diagnose alkaptonuria, health professionals must check the patient’s family history and a clinical evaluation by observing the symptoms. To find the signs, healthcare providers must inspect the urine to see whether it will turn black or not, but there is more than merely observing the urine. There is a test to see if there are high homogentisic acid levels called gas chromatography-mass spectrometry analysis. In addition to the diagnosis, healthcare providers may perform a molecular genetic test to identify mutations in the HGD gene.
Treatment
Unfortunately, there isn’t a fixed treatment for alkaptonuria yet. Many patients take medications to reduce their symptoms, such as anti-inflammatory medications or narcotics for joint pain. A couple of patients would go to a physical or occupational therapist to maintain their joints’ flexibility and strength. Another treatment would be a surgery that involves the joints, hip, and/or knee. Unfortunately, diet restrictions are ineffective for patients. Even if they are in a diet, it would be hard to maintain for the rest of your life as it requires limiting protein (an essential nutrient) completely.
Future Medication
Although there isn't an effective treatment, a drug is being investigated to be tested on patients affected with alkaptonuria called nitisinone. This drug was shown to reduce homogentisic acid levels in the body, which is the leading cause of alkaptonuria. If this drug is released for public use, this can be the perfect medication for affected patients with alkaptonuria.
Check out these resources for more information.
Resources
Introne, W and NORD - National Organization for Rare Disorders. (2017, June 26). Alkaptonuria. NORD (National Organization for Rare Disorders). https://rarediseases.org/rare-diseases/alkaptonuria/#:%7E:text=Alkaptonuria%20is%20a%20rare%20genetic,black%20when%20exposed%20to%20air