Alkaptonuria (AKU)
Description
Alkaptonuria (AKU), also known as black urine disease, is a rare inherited metabolic disorder. It‘s caused by a deficiency in the enzyme homogentisate 1,2-dioxygenase (HGD), leading to a buildup of homogentisic acid (HGA) in the body. This accumulation causes various symptoms, including dark urine, ochronosis (a dark pigmentation of connective tissues), and joint pain.
Genes Involved
Alkaptonuria is caused by mutations in the HGD gene, located on chromosome 3. This gene provides instructions for making the enzyme homogentisate 1,2-dioxygenase (HGD), which plays a crucial role in the breakdown of tyrosine, an amino acid.
Recognizing the Signs and Symptoms
The most noticeable sign of AKU is dark urine, often described as black or brown. This discoloration occurs because the body cannot break down HGA, which is excreted in urine. Other symptoms include:
- Ochronosis: A bluish-black discoloration of cartilage, tendons, and other connective tissues, often affecting the ears, nose, and eyes.
- Joint pain: AKU can cause arthritis-like pain and stiffness in joints, particularly the spine, hips, and knees.
- Cardiovascular issues: In severe cases, HGA buildup can affect heart valves and arteries, increasing the risk of heart disease.
- Kidney stones: HGA can contribute to the formation of kidney stones.
Causes
Alkaptonuria is an autosomal recessive disorder, meaning that both parents must carry the mutated gene for a child to inherit the condition. If both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit AKU.
Inheritance/recurrence risk
AKU is inherited in an autosomal recessive manner. This means that both parents must carry the mutated gene for a child to inherit the condition. If both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit AKU. If one parent has AKU and the other is a carrier, there is a 50% chance with each pregnancy that their child will inherit AKU.
