Alkaptonuria: Year of the Zebra

Alkaptonuria is a rare genetic metabolic disorder that causes a deficiency in the homogentisate 1,2 dioxygenase, or HGD, enzyme and is characterized by the accumulation of homogentisic acid, or HGA, in the body.

Alkaptonuria is inherited in an autosomal recessive pattern, meaning that two copies of the defective gene are required to cause the disorder.

Normally, HGA is converted, by the HGD enzyme, within the body and used for cellular processes. In alkaptonuria, the absence of the HGD enzyme leads to excess HGA being turned into hyperpigmented substances that accumulate in various tissues.Now, alkaptonuria most commonly presents with manifestations in the urine, skin, and joints from HGA accumulation.

The most common symptom is the presence of dark brown or black urine. Excess HGA that gets excreted in the urine is then exposed to the air, which can turn the urine black after time.

In affected infants, this may appear as black stains in diapers.In the skin, blue-black areas of hyperpigmentation appear, usually on ear cartilage or sclera of the eye.

These hyperpigmented areas are called ochronosis.Lastly, in the joints, arthritis occurs, most commonly the low back, hips, knees, and shoulders, and leads to pain and decreased joint mobility.Other body systems may also be involved and include the cardiac, respiratory, and neurologic systems.So, the diagnosis of alkaptonuria is based on the individual’s medical history, characteristic clinical presentation, and can be confirmed with a urine sample showing elevated levels of homogentisic acid.

Additional imaging may be ordered to identify involvement of other body systems, like the joints, heart, or lungs. Genetic testing can also be done to identify mutations in the HGD gene.Now, there’s no cure for alkaptonuria, but there are treatments to help manage levels of HGA and symptoms of the disease.

Nitisinone, a relatively new oral medication that decreases levels of HGA in the blood, is currently approved for use in the European Union.

Nitisinone blocks the enzyme responsible for creating HGA. Treatments for symptoms associated with alkaptonuria may include analgesics for pain, physical and occupational therapy to maintain mobility, medications to treat cardiac or respiratory problems, or even surgery, in some cases.Alright, as a quick recap, alkaptonuria is a rare genetic metabolic disorder that causes a deficiency in the homogentisate 1,2 dioxygenase enzyme leading to the accumulation of homogentisic acid in tissues.

Common clinical manifestations include dark brown or black urine, hyperpigmentation of the skin, and arthritis. Diagnosis is based on the individual’s medical history, physical examination, and laboratory testing.

Treatment aims to relieve symptoms.