About homogentisic acid oxidase deficiency
What is homogentisic acid oxidase deficiency?
Alkaptonuria is a rare genetic metabolic disorder characterized by the accumulation of homogentisic acid in the body. Affected individuals lack enough functional levels of an enzyme required to breakdown homogentisic acid. Affected individuals may have dark urine or urine that turns when exposed to air. However, this change may not occur for several hours after urination and often goes unnoticed. Aside from dark urine that is present from infancy, affected individuals generally do not develop symptoms (asymptomatic) during infancy or childhood and often remain unaware of their condition until adulthood. Affected individuals eventually develop ochronosis, which is the bluish- discoloration of connective and other tissue within the body. Affected individuals may develop discoloration of the skin overlying cartilage within the body such as over part of the outer ear. In some cases, the whites of the eyes (sclera) may also become discolored. In adulthood, affected individuals also develop progressive arthritis of the spine and large joints. The HDG gene codes for the enzyme required for the breakdown of homogentisic acid. Mutations in HDG cause alkaptonuria.
What are the symptoms for homogentisic acid oxidase deficiency?
Dark stains on a baby’s diaper are one of the earliest signs of alkaptonuria. There are few other symptoms during childhood. Symptoms become more obvious as you age.
Your urine may turn dark brown or when it’s exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis.
For example, you may notice chronic stiffness or Pain in your lower back or large joints.
Other symptoms of alkaptonuria include:
- 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
- kidney stones and prostate stones
- arthritis (especially hip and knee joints)
Alkaptonuria can also lead to heart problems. The buildup of homogentisic acid causes your heart valves to harden. This can keep them from closing properly, resulting in aortic and mitral valve disorders.
In severe cases, heart valve replacement may be necessary. The buildup also causes your blood vessels to harden. This raises your risk of high blood pressure.
What are the causes for homogentisic acid oxidase deficiency?
Alkaptonuria is caused by a mutation on your homogentisate 1,2-dioxygenase (HGD) gene. It’s an autosomally recessive condition.
This means that both of your parents must have the gene in order to pass the condition on to you.
Alkaptonuria is a rare disease. According to the National Institutes of Health, the condition affects about 1 in 250,000 to 1 million people worldwide, but is more common in Slovakia and the Dominican Republic, affecting about 1 in 19,000 people.
What are the treatments for homogentisic acid oxidase deficiency?
There’s no specific treatment for alkaptonuria. Instead, treatment is focused largely on managing symptoms.
There are many therapies that have been tried, but unfortunately they haven’t been proven to be effective, and may be harmful or unhelpful in the long term.
However, The National Institutes of Health warns that long-term use of vitamin C can sometimes increase the production of kidney stones and has generally proven ineffective for long-term treatment of this condition.
Other treatments for alkaptonuria are focused on preventing and relieving possible complications, such as:
- heart disease
- kidney stones
For example, your doctor may prescribe anti-inflammatory medications or narcotics for joint pain. Physical and occupational therapy may help you maintain flexibility and strength in your muscles and joints.
You should also avoid activities that put a lot of strain on your joints, such as heavy manual labor and contact sports. At some point in your life, you might need surgery.
The World Institutes of Health reports adults can experience a buildup of homogentisic acid in cartilage, resulting in arthritis. As a result those with alkaptonuria may need a shoulder, knee, or hip replacement.
You may also require surgery to replace your aortic or mitral heart valves, if they stop working properly. In some cases, you may need surgery or other therapies to treat chronic kidney or prostate stones.
What are the risk factors for homogentisic acid oxidase deficiency?
Risk factors of Homogentisic acid oxidase deficiency:
1. Homogentisic acid oxidase deficiency is an autosomal recessive condition that is inherited. When a person receives the same defective gene for the same trait from both parents, recessive genetic diseases develop. A person will be a carrier for the disease if they have one normal gene and one sick gene, although they often won't exhibit any symptoms.
2. With each pregnancy, there is a 25% chance that two carriers will carry the faulty gene to their offspring and cause them to be impaired. Each pregnancy carries a 50% chance of passing the gene to the unborn child. A child has a 25% probability of inheriting normal genes from both parents and being genetically normal for that specific trait.
3. Both men and women are at the same level of risk. Males and females who have alkaptonuria are also affected, albeit males are more likely to experience earlier onset and worsening of symptoms
Urine that turns dark is present from birth,Ochronosis, in which connective tissue such as cartilage turns blue, gray or due to the chronic accumulation of homogentisic acid,In many individuals, cartilage within the ear may become thickened, irregular and discolored blue, gray or
Accumulation of homogentisic acid in the body
Anti-inflammatory medications,High-doses of vitamin C have also been used to treat alkaptonuria
Is there a cure/medications for homogentisic acid oxidase deficiency?
The life expectancy for people with alkaptonuria is fairly normal. However, the disease puts you at much higher risk of certain disorders, including:
- arthritis in your spine, hips, shoulders, and knees
- tearing of your Achilles tendon
- hardening of your heart’s aortic and mitral valves
- hardening of your coronary arteries
- kidney and prostate stones
Some of these complications can be delayed with regular checkups. Your doctor will want to monitor you regularly. Tests to monitor the progress of your condition might include:
- spinal X-rays to check for disk degeneration and calcification in your lumbar spine
- chest X-rays to monitor your aortic and mitral heart valves
- CT (computed tomography) scans to find signs of coronary artery disease