DRUG INDEX
Alkaptonuria
(Ochronosis)
What is alkaptonuria?
Alkaptonuria is a rare disease that is inherited. The disease results from a deficiency of the enzyme homogentisic acid oxidase. This enzyme deficiency leads to a build up of homogentisic acid in tissues of the body.
Alkaptonuria is known to be especially frequent in Slovakia and in the Dominican Republic. How is alkaptonuria inherited?
Alkaptonuia is a classic recessive condition. The gene for it is on a nonsex (autosomal) chromosome. Parents of a person with alkaptonuria each have one alkaptonuric gene and a normal gene paired with it. They have no symptoms of alkaptonuria at all. Each of their children has a one-quarter (25%) chance to receive both of their normal genes, a one-half (50%) chance to receive one alkaptonuric and one normal gene (and seem entirely normal) and a one-quarter (25%) chance to receive both of their alkaptonuric genes and have alkaptonuria (ochronosis).
What is ochronosis?
Ochronosis is the darkening of the tissues of the body that is caused by pigment composed of the excess homogentisic acid in patients with alkaptonuria. The pigment accumulates in the cartilage of the joints and ears, skin, and whites (sclerae) of the eyes. Bluish discoloration of the nails is also characteristic.
How does alkaptonuria affect the joints?
Alkaptonuria leads to premature progressive degeneration of the cartilage of the joints due to the accumulation of homogentisic acid in the cartilage. This results in osteoarthritis of joints throughout the body at an unusually early age. Typical joints affected include the spine, knees, hips, and shoulders. Joint symptoms include stiffness, pain, swelling, and limited motion.
Other causes of ochronosis that mimic alkaptonuria include the prolonged administration of quinacrine (atabrine) and the use of some bleaching creams used by black women to lighten their complexion (the offending creams contain hydroquinone).
What are symptoms of alkaptonuria (ochronosis)?
Persons affected by alkaptonuria (ochronosis) can note persistent, painless bluish darkening of the outer ears, nose, and whites of the eyes. Symptoms of osteoarthritis can occur at ages that are premature for this form of arthritis , which typically affects persons after the age of 55 years.
Homogentisic acid accumulated in the urine will cause it to turn black. The urine from a person with alkaptonuria turns dark on standing if it is alkaline. (Alkaptonuria was easily diagnosed among the nomadic Bedouin peoples because people with the disease left a characteristic dark spot in the sand marking the spot where they had urinated).
Calcification of cartilage can be detected on x-ray testing. In males, calcification of the prostate gland can occur.
Heart valves can also become diseased due to ochronosis.
How is alkaptonuria (ochronosis) diagnosed?
The doctor will suspect alkaptonuria (ochronosis) when the patient reports the abnormal black color in the urine. Bluish discoloration of the eyes, ears, or nose will also suggest the disease. Elevated levels of homogentisic acid in urine and blood samples confirm the diagnosis.
How is alkaptonuria (ochronosis) treated?
There is no effective treatment for the underlying enzyme deficiency of alkaptonuria. Ascorbic acid (vitamin C) has been found to prevent pigment deposits.
Degenerative joint symptoms are treated as for degenerative arthritis (osteoarthritis) of any cause. Treatment of osteoarthritis is reviewed elsewhere. Sometimes joint surgery can be helpful, including arthroscopy and joint replacement.
Future treatments for alkaptonuria might involve gene alteration therapies.
Where is the alkaptonuria gene and why is the disease unique in genetics (the study of heredity)?
The gene for alkaptonuria has been mapped to chromosome number 3 in the region of bands 3q21- q23. The gene for the enzyme homogentisate 1,2-dioxygenase (HGD) has been found to map to exactly the same location. A human gene known as the HGO gene has proven to be synonymous with HGD. And, most importantly, it is now quite clear that alkaptonuria is due to mutations at this genetic locus (spot) on chromosome 3.
Alkaptonuria enjoys the historic distinction of being one of the conditions for which recessive inheritance was first proposed. This prescient proposal was made in 1902 by the English physician Archibald Garrod, later Sir Archibald. In a series of brilliant lectures in 1908 Garrod set forth the charter group of what he called "inborn errors of metabolism." The 4 conditions he labeled as inborn errors were albinism, cystinuria , pentosuria and, of course, alkaptonuria.
Alkaptonuria is also known as homogentisic acid oxidase deficiency. - Alkaptonuria is a rare inherited (genetic) disorder.
- The gene defect causes accumulation of homogentisic acid.
- The excess homogentisic acid causes dark discoloration of tissues and is known as ochronosis.
- Damage to joints from the excess homogentisic acid can result in the early onset of osteoarthritis.
|
DISCLAIMER:
Information on this site is provided for informational
purposes and is not meant to substitute for the advice
provided by your own physician or other medical professional.
You should not use the information contained herein
for diagnosing or treating a health problem or disease,
or prescribing any medication. You should read carefully
all product packaging. Not all Canadian drugs, Canada
prescription and Canadian prescription medicine is available
at discount Canadian on line pharmacies. If you have
or suspect that you have a medical problem, promptly
contact your health care provider. Information and statements
regarding diet supplements have not been evaluated by
Health Canada and are not intended to diagnose, treat,
cure, or prevent any disease. All trade and service
marks mentioned on this site are recognized as belonging
to their respective owners.
|
|
|
|
