The person suffering from Alkaptonuria, is usually advised a heavy dose of ascorbic acid Ascorbic acid is used to prevent or treat low levels of vitamin C in people who do not get enough of the vitamin from their diets.ascorbic acid (vitamin C)
Full Answer
What is alkaptonuria and how to treat it?
The person suffering from Alkaptonuria, is normally prescribed a heavy dose of ascorbic acid or vitamin C so that the process of HGD accumulation in your body slows down, although excessive use of vitamin C may not prove to be effective in the treatment. The person may also be recommended a low-protein diet.
Is nitisinone an effective treatment for alkaptonuria?
Investigational Therapies. Researchers are studying the use of a drug known as nitisinone (Orfadin®) as a potential treatment for alkaptonuria. Nitisinone, which received orphan drug status in 2001 from the Food and Drug Administration (FDA), has been approved for the treatment of a metabolic disorder known as tyrosinemia.
Does vitamin C help alkaptonuria?
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:
What are the treatment options for alkaptonuria (black urine disease)?
Alkaptonuria (Black Urine Disease) Treatment & Management 1 Medical Care. In infancy, a history of dark-stained diapers should alert... 2 Surgical Care. Older individuals may require removal of lumbar discs with fusion. 3 Consultations. 4 Diet. Reduction of phenylalanine and tyrosine reportedly reduced homogentisic acid excretion in...
What is the treatment of 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.
How does vitamin C help in alkaptonuria?
Vitamin C, as much as 1 g/d, is recommended for older children and adults. The mild antioxidant nature of ascorbic acid helps to retard the process of conversion of homogentisate to the polymeric material that is deposited in cartilaginous tissues.
How can you prevent alkaptonuria?
Prevention. Genetic counseling is recommended for people with a family history of alkaptonuria who are considering having children. A blood test can be done to see if you carry the gene for alkaptonuria.
Which of the following analyte is used for the diagnosis of alkaptonuria?
Your doctor can use a test called gas chromatography to look for traces of homogentisic acid in your urine. They can also use DNA testing to check for the mutated HGD gene. Family history is very useful in making a diagnosis of alkaptonuria.
Which enzyme is deficient in alkaptonuria?
Alkaptonuria is caused by a deficiency of the enzyme homogentisate 1,2-dioxygenase (HGD), the third enzyme of the tyrosine degradation pathway (Figure 2). Biallelic pathogenic variants in HGD lead to significantly decreased enzyme function. Deficiency of HGD causes accumulation of homogentisic acid (HGA).
What causes 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 common is alkaptonuria?
Alkaptonuria is a rare (approximately 1 in 250,000 live births) autosomal recessive disorder caused by a deficiency of homogentisate 1,2-dioxigenase. Large amounts of homogentisic acid are formed (seeFig. 103.1), which are excreted in urine or deposited in tissues.
How are inborn errors of metabolism treated?
The management of inborn errors of metabolism has traditionally consisted in diet therapy and supportive therapy, but recently other treatment options have become available, including enzyme and coenzyme replacement, removal of harmful substances, cell and organ transplantation, and gene therapy.
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.
Why Benedict test is positive in alkaptonuria?
Reducing sugar, Ascorbic acid, High level of uric acid or glucuronide may give Benedict's test positive. Result should be counter checked with Uristrip / Dipstrip for Glucose. Alkaptonuria gives Uristrip test negative.
What is alkaptonuria biology?
Alkaptonuria is a recessive abnormality, having a rate of about 3-5:1000000. It is caused by a deficiency of the Homogentisate acid oxidase enzyme. Signs of the disease are special staining of cartilages and arthritis in the elderly.
What does homogentisic acid oxidase do?
Homogentisate oxidase is responsible for a specific step in the breakdown of phenylalanine and tyrosine. Previous steps convert the two amino acids into a molecule called homogentisic acid. Homogentisate oxidase adds two oxygen atoms to homogentisic acid, converting it to another molecule called maleylacetoacetate.
What is the best treatment for alkaptonuria?
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.
How many people are affected by alkaptonuria?
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 test can be used to test for homogentisic acid in urine?
They may also test you for the condition if you develop early onset osteoarthritis. Your doctor can use a test called gas chromatography to look for traces of homogentisic acid in your urine. They can also use DNA testing to check for the mutated HGD gene. Family history is very useful in making a diagnosis of alkaptonuria.
Is there a cure for alkaptonuria?
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.
Can alkaptonuria cause heart problems?
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.
How to treat alkaptonuria?
Joint pain may be substantial in individuals with alkaptonuria, and close attention to pain control is usually necessary. Physical and occupational therapy can be important to promote muscle strength and flexibility. Knee, hip, and shoulder replacement surgeries may be options for managing significant arthritis. In general, however, the goal of joint replacement is pain relief rather than increased range of motion. Maintaining joint range of motion through moderate non-weight-bearing exercise such as swimming may have beneficial effects. Treatment of prostate stones and renal stones may include surgery. [4]
What is the name of the substance that turns black in the urine?
Listen. The three main features of alkaptonuria (AKU) are the presence of a substance called homogentisic acid (HGA) in the urine, ochronosis and arthritis. The urine of individuals with AKU turns black when exposed to air. Children do not have symptoms of AKU other than the urine turning black when left to stand for a few minutes.
What do healthcare professionals look for in a diagnosis?
Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition.
Does AKU cause black urine?
Children do not have symptoms of AKU other than the urine turning black when left to stand for a few minutes. Ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, is also characteristic of the disorder.
Is alkaptonuria inherited?
Alkaptonuria is caused by mutations in the HGD gene. It is inherited in an autosomal recessive fashion. [1] . There is still no cure for this disease. Treatment includes the management of joint pain, physical and occupational therapy, joint replacements and surgery when needed. Last updated: 3/18/2016.
How is the treatment done?
Alkaptonuria, also known as the Black Urine Disease, is an unusual inherited disorder where the body becomes unable to produce Homogentisic Dioxygenase (HGD) enzyme resulting in accumulation of homogentisic in your body. As a result of this, your bones and cartilage become fragile and discolored.
Who is eligible for the treatment? (When is the treatment done?)
Alkaptonria is a rare genetic disorder following an autosomal recessive pattern wherein both the genes in each cell undergo mutation. Hence people having a genetic history of HGD gene mutation are prone to this disease which basically implies that both the parents must have HGD genes in order for the child to inherit the condition.
Who is not eligible for the treatment?
Alkaptonria is a rare genetic disorder following an autosomal recessive pattern wherein both the genes in each cell undergo mutation. Hence people having a genetic history of HGD gene mutation are prone to this disease which basically implies that both the parents must have HGD genes in order for the child to inherit the condition.
Are there any side effects?
There are no specific restrictions to the treatment of Alkaptonuria. Anybody not showing signs and symptoms of urine discoloration and joint pain are not eligible for the treatment.
How long does it take to recover?
The post treatment guidelines include certain measures as following proper medication and dietary plan in order to avoid urine infection, being physically active in order to avoid joint pain and muscle flex.
What is the price of the treatment in India?
Although recovering from alkaptonuria does not take much time if the prescribed medication and post treatment guidelines are followed, it may lead to arthritis in the long run.
Are the results of the treatment permanent?
The cost of treatment for alkaptonuria roughly ranges between Rs.500- Rs. 1000, and is easily affordable.
Summary
Alkaptonuria is caused by deficiency of homogentisate 1,2-dioxygenase, an enzyme that converts homogentisic acid (HGA) to maleylacetoacetic acid in the tyrosine degradation pathway.
Diagnosis
No consensus clinical diagnostic criteria for alkaptonuria have been published.
Clinical Characteristics
The clinical findings of alkaptonuria include connective tissue ochronosis and arthritis of the spine and larger joints. Urinary excretion of homogentisic acid (HGA) and disease severity can vary significantly within the same family.
Differential Diagnosis
Ochronosis. Ochronosis resulting from alkaptonuria may be confused with acquired, reversible pigmentary changes following prolonged use of carbolic acid dressings for chronic cutaneous ulcers [ La Du 2001 ].
Genetic Counseling
Genetic counseling is the process of providing individuals and families with information on the nature, mode (s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions.
Resources
GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.
Molecular Genetics
Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. — ED.
General information
Alkaptonuria (homogentizine aciduria, hereditary ochronosis) is a hereditary pathology of metabolism, which is based on a violation of tyrosine metabolism, leading to excessive formation of an intermediate metabolite – homogentizic acid.
Causes of alkaptonuria
Alkaptonuria is one of the genetically determined enzymopathies inherited by an autosomal recessive type, i.e. for the development of clinical manifestations of the disease, a child must receive from each of the parents one copy of the mutant gene.
Symptoms of alkaptonuria
Alkaptonuria is characterized by the following main symptom complexes: homogentizine aciduria, ochronosis and arthropathy. These signs occur at different times: urine staining exists from birth, tissue pigmentation becomes pronounced by the age of 30, joint damage develops in the fourth decade of life.
Diagnostics
Most often, alkaptonuria is diagnosed in early childhood, but in some cases it can be detected only as the full symptom complex develops. It is important to indicate the excretion of urine, darkening in the air; the presence of pigmentation and compaction of the skin; progressive damage to the spine and joints.
Treatment of alkaptonuria
Etiopathogenetic therapy of genetic alkaptonuria has not been developed to date. To prevent excessive formation of homogentizic acid, some authors point to the expediency of following a low-protein diet. In order to improve tyrosine metabolism in alkaptonuria, vitamin C intake is indicated .
Forecast
The prognosis for the cure of alkaptonuria is unfavorable. The disease has a chronic progressive course with the development of irreversible changes in the body. The outcome of alkaptonuria is persistent disability of the patient. The genetic nature of the pathology does not allow us to talk about the possibility of specific prevention.
Symptoms
- Alkaptonuria is a genetic disorder, and urine that turns dark is present from birth. However, additional symptoms usually do not appear until adulthood. Symptoms are generally slowly progressive. The urine of individuals with alkaptonuria may be abnormally dark or it may turn bla…
Signs and symptoms
- The first noticeable signs and symptoms of alkaptonuria usually do not develop until approximately 30 years of age and are due to chronic accumulation of homogentisic acid in connective tissue, especially cartilage. Affected individuals develop a condition called ochronosis, in which connective tissue such as cartilage turns blue, grey or black due to the chronic accumul…
Pathophysiology
- In addition to cartilage, homogentisic acid accumulates in other connective tissue including tendons and ligaments and even bone. Over time, affected tissue becomes discolored, brittle and weak. Affected individuals may develop abnormalities affecting the tendons including thickened Achilles tendons and inflammation of the tendons (tendonitis). Affected tendons and ligaments …
Prognosis
- Alkaptonuria does not cause developmental delays or cognitive impairment and does not appear to affect life span. However, chronic pain and mobility issues can develop.
Genetics
- Alkaptonuria is inherited as an autosomal recessive trait. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the d…
Epidemiology
- Alkaptonuria affects males and females in equal numbers, although symptoms tend to develop sooner and become more severe in males. More than 1,000 affected individuals have been reported in the medical literature. The exact incidence of alkaptonuria is unknown. In the United States it is estimated to occur in 1 in 250,000-1,000,000 live births. Alkaptonuria has been report…
Diagnosis
- Symptoms of the following disorders can be similar to those of alkaptonuria. Comparisons may be useful for a differential diagnosis. The diagnosis of alkaptonuria is made upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Identification of vastly elevated levels of homogentisic acid in the urine is indi…
Causes
- Ochronosis can also occur as a reversible, acquired condition that is unrelated to alkaptonuria. In such cases, ochronosis occurs secondary to exposure to a variety of substances including benzene, phenol and trinitrophenol. Individuals have also developed ochronosis following long-term use of certain medications including the antimalarial drug Atabrine®, the skin-lightening ag…
Contraindications
- Activities that place significant physical stress to the spine and joints such as high impact sports or heavy manual labor should be avoided.
Research
- Researchers are studying the use of a drug known as nitisinone (Orfadin®) as a potential treatment for alkaptonuria. Nitisinone, which received orphan drug status in 2001 from the Food and Drug Administration (FDA), has been approved for the treatment of a metabolic disorder known as tyrosinemia. In earlier studies, nitisinone was shown to significantly reduce accumulat…
Resources
- Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
Literature
- Zatkova A. An update on the molecular genetics of alkaptonuria. J Inherit Metab Dis. 2011; [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/21720873 Introne WJ, Perry MB, Troendle J, et al. A 3-year randomized therapeutic trial of nitisinone in alkaptonuria. Mol Gene Metab. 2011;103:307-314. http://www.ncbi.nlm.nih.gov/pubmed/21620748