What are some effective treatments for alkaptonuria?
Alkaptonuria is a lifelong condition – there’s currently no specific treatment or cure. However, a medicine called nitisinone has shown some promise, and painkillers and lifestyle changes may help you cope with the symptoms.
What enzyme is involved in alkaptonuria?
Alkaptonuria is caused by mutation of the homogentisate 1,2-dioxygenase (HGD) gene. The HGD gene contains instructions for creating (encoding) an enzyme known as homogentisate 1,2-dioxygenase. This enzyme is essential for the breakdown of homogentisic acid.
How does NTBC reduce the symptoms of alkaptonuria?
Nitisinone (NTBC) has been shown to effectively treat alkaptonuria by blocking the conversion of 4-hydroxyphenylpyruvate to HGA, but there have been concerns that using doses higher than about 2 mg/day could cause excessively high levels of tyrosine, resulting in crystal deposition and corneal pathology.
Which amino acid metabolism is affected in alkaptonuria?
A defect in the HGD gene causes alkaptonuria. The gene defect makes the body unable to properly break down certain amino acids (tyrosine and phenylalanine). As a result, a substance called homogentisic acid builds up in the skin and other body tissues.
What causes bones to turn black?
One is that the discoloration occurs when bone is cut and hemoglobin is released to the surface of the cut bone where it will accumulate. Over time and through exposure to air, hemoglobin on the surface of the bone turns from red to brown to black.
How does vitamin C help in alkaptonuria?
Ascorbic acid (ASC), more commonly known as vitamin C, is an antioxidant believed to reduce the conversion of HGA to BQA via oxidation. However, investigation revealed that although ASC reduced the HGA to BQA conversion, it did not affect HGA urinary excretion.
What causes black bone disease?
Alkaptonuria (AKU) is also known as Black Bone Disease. This is because an acid in the body accumulates at 2,000 times the normal rate, attacking the bones and turning them black and brittle. It causes severely debilitating osteoarthritis, heart disease, and other serious health complications.
Where does homogentisic acid come from?
Homogentisic acid (2,5-dihydroxyphenylacetic acid) is a phenolic acid usually found in Arbutus unedo (strawberry-tree) honey. It is also present in the bacterial plant pathogen Xanthomonas campestris pv. phaseoli as well as in the yeast Yarrowia lipolytica where it is associated with the production of brown pigments.
Why is my urine turning black?
Alkaptonuria is an inherited condition that causes urine to turn black when exposed to air. Ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, is also characteristic of the disorder. This blue-black pigmentation usually appears after age 30.
What are some symptoms of having alkaptonuria?
What are the symptoms of alkaptonuria?
- dark spots in the sclera (white) of your eyes.
- thickened and darkened cartilage in your ears.
- blue speckled discoloration of your skin, particularly around sweat glands.
- dark-colored sweat or sweat stains.
- black earwax.
- kidney stones and prostate stones.
What is the role of homogentisic acid?
Homogentisic acid is a dihydroxyphenylacetic acid having the two hydroxy substituents at the 2- and 5-positions. It has a role as a human metabolite and a plant metabolite.
What is black bone disease?
Alkaptonuria, also known as AKU or Black Bone Disease, is an extremely rare genetic condition, which can cause significant damage to the bones, cartilage and tissues of those affected. AKU normally only affects one in every 250,000 people worldwide.
How is homogentisic acid formed in the body?
Homogentisic acid, also known as melanic acid, is an intermediate in the breakdown or catabolism of tyrosine and phenylalanine. It is generated from the compound p-hydroxyphenylpyruvate through the enzyme p-hydroxyphenylpyruvate dehydrogenase.
Can osteonecrosis heal itself?
Osteonecrosis heals without treatment in some people if the disorder is diagnosed early and if the affected area is small and not in the major weight-bearing area. Spontaneous osteonecrosis of the knee is usually treated without surgery, and pain usually resolves.
Can osteonecrosis be reversed?
Treatment can slow the progress of avascular necrosis, but there is no cure. Most people who have avascular necrosis eventually have surgery, including joint replacement. People who have avascular necrosis can also develop severe osteoarthritis.
Does ascorbic acid increase excretion of benzoquinone acetic acid from urine?
The administration of relatively large amounts of ascorbic acid to the adults was followed by a disappearance of benzoquinone acetic acid from the urine, whereas the level of excretion of homogentisic acid did not change. This could have relevance to the pathogenesis of ochronotic arthritis.
What is the pathophysiology of alkaptonuria?
Alkaptonuria is characterized by deficiency of homogentisate 1,2-dioxygenase, which converts homogentisic acid (HGA) to maleylacetoacetic acid. Mechanism of disease causation. Loss of function
What causes ochronotic pigmentation in alkaptonuria?
Ochronotic pigmentation is caused by homogentisic acid and is the key event in alkaptonuria leading to the destructive consequences of the disease-A review. J Inherit Metab Dis. 2019;42:776–92.
How is joint pain managed in patients with alkaptonuria?
Joint pain is substantial in individuals with alkaptonuria, and close attention to pain control is necessary. Optimal pain management should be tailored to the individual with close follow up and long-term management. Physical and occupational therapy are important to promote optimal muscle strength and flexibility.