Alcaptonuria
The content of the article:
- Causes
- Symptoms
- Diagnostics
- Treatment
- Possible complications and consequences
- Forecast
- Prevention
Alcaptonuria is a hereditary disease based on a violation of amino acid metabolism associated with the absence of the enzyme homogentisinase in the body. This leads to the fact that the metabolism of amino acids ends at the stage of formation of homogentisic acid. This metabolite is excreted through the kidneys, and also accumulates in various tissues (sclera, tendons, articular cartilage, skin, etc.).
Alcaptonuria is rare. It is diagnosed with a frequency of 1 in 500,000 people. According to medical statistics, the disease is most often detected in males living in the United States, the Dominican Republic, Slovakia, the Czech Republic, Germany and India.
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Causes
Alcaptonuria is an enzymopathy caused by genetic (hereditary) causes. It is inherited in an autosomal recessive manner. This means that for the disease to occur, the child must receive the mutant gene from both the father and mother. If he receives a pathological gene from one of the parents, then the disease will not develop and the exchange of amino acids will be normal, but the child will be the carrier of the altered gene and can later pass it on to the offspring.
The mutation leading to the development of alkaptonuria affects the gene located on the long arm of the third chromosome (3q 21-23), which is responsible for the synthesis of homogentisinic acid oxidase (homogentisinase). The named enzyme is essential for the proper metabolism of phenylalanine and tyrosine. Normally, when these amino acids are cleaved, an intermediate substance is formed - homogentisinic acid, which is then converted under the influence of homogentisinase into maleylacetoacetic acid, which decomposes into fumaric and acetoacetic acids. These two acids are further used in various biochemical cycles.
In the body of patients with alkaptonuria, homogentisinase is absent. This leads to the fact that homogentisic acid cannot undergo further decomposition. It turns into the pigment alkapone (quinone polyphenol), which can be deposited in various tissues. Alcaptone is excreted in large quantities from the body by the kidneys, hence the name of the disease, which literally translates as "urine alkapone".
Symptoms
It is possible to suspect the presence of alkaptonuria in a child already in the first days of his life on the basis of the characteristic staining of urine and the appearance of dark stains on wet diapers, which are almost impossible to remove. When standing, urine very quickly acquires a dark color, which is explained by the high content of homogentisic acid in it. Over time, alkaptonuria leads to urolithiasis, chronic pyelonephritis and calculous prostatitis.
By the age of 30 in patients with alkaptonuria, skin syndrome becomes clearly visible:
- gray-brown pigmentation of the skin in the face, neck, armpits, abdomen, palms and groin;
- gray-blue coloration and hardening of the auricles;
- gray-blue pigmentation of the conjunctiva and sclera.
External manifestations of alkaptonuria in people of different ages
Alcapton is also deposited in the cartilage of the larynx, which over time leads to pain when swallowing, dysphagia, shortness of breath, and hoarseness.
Alcaptonuria is often complicated by atherosclerosis and calcification of the aorta, the development of mitral and (or) aortic valve defects. It can also be deposited in other organs (spleen, pancreas, testes, adrenal glands, thyroid gland), which leads to disruption of their functions.
After 35–40 years, patients with alkaptonuria manifest lesions of the musculoskeletal system. Initially, the spine and large joints are involved in the pathological process. Deforming spondylosis develops in the thoracic and lumbar spine. The severity of lumbar lordosis gradually decreases, stiffness occurs during movement, and back pain appears.
The deposition of alkapton in the articular tissue causes deforming osteoarthritis, affecting the hip, shoulder and knee joints. This articular pathology is characterized by:
- reactive synovitis (swelling of the affected joints);
- crepitus;
- limitation of mobility;
- the formation of flexion contracture.
Also, with alkaptonuria, damage to the pubic articulation and sacroiliac joints is often observed.
Diagnostics
In most cases, alkaptonuria is diagnosed in the first years of a child's life. A triad of signs has an important diagnostic value:
- Rapid darkening of urine in air.
- Thickening and pigmentation of the skin.
- Progressive damage to the articular apparatus - primarily the large joints and the spine.
To confirm the diagnosis and identify possible complications, a number of laboratory and instrumental studies are performed, consultations of related specialists are also shown.
Instrumental examination includes:
- X-ray of the spine and large joints;
- diagnostic arthroscopy;
- pyelography;
- Ultrasound of joints, kidneys, bladder, prostate;
- USDG of the aorta;
- Echocardiography;
- laryngoscopy.
Biochemical examination of urine using the method of liquid chromatography or spectrophotometry allows for the pathogenetic diagnosis of alkaptonuria, based on the detection of benzoquinoacetic and homogentisic acids in the urine.
The color of urine, as well as its rapid darkening when alkalinized, boiled or stored outdoors, are of diagnostic value.
Diagnosis of alkaptonuria is not difficult due to the rapid darkening of urine in the air
If necessary, a study of the synovial (articular) fluid is carried out. In it, particles of ochronotic pigment are detected, while there are no signs of an inflammatory process. Joint biopsy with subsequent histological analysis reveals changes characteristic of alkaptonuria.
Alcaptonuria requires differential diagnosis with the following diseases:
- lipoproteinosis;
- argyrosis;
- amyloidosis;
- porphyria;
- ankylosing spondylitis;
- osteochondrosis.
Alcaptonuria can occur not only as an independent disease, but also as a symptom of severe vitamin C hypovitaminosis. In this case, the appointment of high doses of ascorbic acid leads to the elimination of urinary excretion of alkapone.
Treatment
With alkaptonuria, many organs and systems are affected, therefore, doctors of various specializations are involved in its treatment: genetics, cardiac surgeons, urologists, nephrologists, orthopedists, dermatologists, rheumatologists.
There is no specific treatment. Some experts recommend that patients follow a protein-restricted diet as this can help reduce excess homogentisic acid production.
High doses of ascorbic acid can improve the metabolism of tyrosine, therefore their appointment is justified.
For alkaptonuria, a low protein diet and high doses of ascorbic acid are indicated
Basically, drug treatment is aimed at eliminating the existing pathological symptoms, that is, it is symptomatic. The therapy regimen includes:
- antispasmodics;
- non-steroidal anti-inflammatory drugs;
- chondroprotectors;
- physiotherapy (paraffin baths, mud therapy, radon baths);
- physiotherapy exercises;
- massage.
Possible complications and consequences
As the disease progresses, the deformity of large joints becomes so pronounced that the patient's mobility is significantly limited. In such situations, orthopedic surgery is indicated, which consists in replacing the affected joints with artificial ones, that is, joint arthroplasty.
Damage to the valvular apparatus of the heart in alkaptonuria can lead to significant hemodynamic disturbances. It is not always possible to eliminate them with medication; in this case, they resort to prosthetics of the aortic or mitral valve.
Forecast
Alcaptonuria is a genetic disease that currently cannot be cured. It has a progressive chronic course, irreversible disorders in many internal organs gradually develop, which leads to persistent disability.
Prevention
There is no specific prophylaxis. If there have been cases of alkaptonuria in the family, a geneticist is required at the planning stage of pregnancy.
Elena Minkina Doctor anesthesiologist-resuscitator About the author
Education: graduated from the Tashkent State Medical Institute, specializing in general medicine in 1991. Repeatedly passed refresher courses.
Work experience: anesthesiologist-resuscitator of the city maternity complex, resuscitator of the hemodialysis department.
The information is generalized and provided for informational purposes only. At the first sign of illness, see your doctor. Self-medication is hazardous to health!
