Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The rare disease that we will be learning about today is:

Alkaptonuria

Sometimes called black urine disease or black bone disease.

What is Alkaptonuria?

• Alkaptonuria is a rare, inherited genetic disorder in which a substance called homogentisic acid accumulates in the tissues and blood
• This substance eventually damages cartilage and is also excreted in the urine, resulting in an unusual dark coloration
• While rare, alkaptonuria is more common in certain regions, such as the Dominican Republic and Slovakia
• Incidence rate of the disorder is around one in 250,000 people
• A diagnosis of alkaptonuria can be confirmed by collecting urine and leaving it exposed to open air; if the patient has the disorder, the urine will turn brownish or black
• Alkaptonuria was first described by Archibald Edward Garrod in 1902

How Do You Get It?

• This rare genetic disease is the result of a mutation in the gene HGD, which codes for the enzyme homogentisate 1,2-dioxygenase
• This is an autosomal recessive disease, meaning that both parents must pass along the mutation

What Are The Symptoms?

• Aside from urine that darkens with air exposure, people born with alkaptonuria do not initially experience any symptoms. However, beyond age 30, a greater range of signs and symptoms begin to develop. These symptoms can include:
• Pigmentation in the ear cartilage and in the corneal limbus/sclera of the eye
• Loss of bone mineral density, increasing risk of breaks
• Pain in the weight-bearing joints, such as the knees, hips, and spine
  • Pain may be severe and disabling, affecting daily activities
  • If the spine is affected, this can impact movement of the rib cage, causing breathing problems
• Valvular heart disease
• Heart failure
• Heart rhythm abnormalities
• Kidney stones
• Hearing loss
• Gallstones
• Stones in the salivary gland or prostate

How Is It Treated?

• No treatment approach has been decisively proven to reduce the complications of alkaptonuria
• A primary goal of treatment is to reduce the buildup of homogentisic acid
  • Approaches include restricting amino acids in the diet and supplementation of vitamin C
  • Unfortunately, the effectiveness of these methods have never been demonstrated
• Some research has suggested that nitisinone, an herbicide, could help treat alkaptonuria
  • Nitisinone can prevent the production of homogentisic acid
  • However, high doses can cause a buildup of tyrosine, which has unclear consequences
    • Eye damage is a significant concern and frequent monitoring is necessary for those receiving this treatment in the long term
• Alkaptonuria does not seem to have an impact on lifespan, but quality of life can be greatly impacted
• Many patients will require joint replacement surgery by age 50-55

Where Can I Learn More???

• Learn more about this disease from the National Organization for Rare Disorders.
• Check out our cornerstone on this disease here.