Alcaptonuria is a very rare genetic disease that occurs only in 1 case per 500 thousand people. It is associated with a mutation of the HGD gene. It is noted that the disease occurs most often in the Czech Republic, Slovakia, India, the United States and Germany. The disease is more common in men.
The pathology was first described as early as 1584, but the essence of the disease was fully determined only in the 19th century. Two scientists, Volkov M. and Bayman E., managed to isolate alkapton crystals from urine.
Pathology Features
The disease is a consequence of the release of homogentizinic acid. It stops the metabolism of amino acids. It is an intermediate decomposition product of tyrosine and phenylalanine. Subsequently, the metabolite accumulates in the body. It is a decomposition product of homogentisic acid.
The substance is concentrated in the joints, mainly large, in the skin, in the organs of the endocrine system, in cartilage, in the heart muscle and even in the sclera of the eyes. As a result, the tissues or organs where this product has accumulated pigment, or rather, acquire a dark color. This type of pigmentation is called ochronosis, which leads to the accumulation of calcium and subsequently to ossification.
For example, if the pathology manifests itself on the auricle, then a seal appears with a grayish-bluish color. If we are talking about the spine, spondylosis is formed. With the accumulation of substances in the joints, a disease called ochronotic osteoarthrosis appears. With the accumulation of the metabolite in the heart muscle, myocardial infarction may form.
Development reasons
Pathology is a completely genetic disorder. Alcaptonuria is inherited as an autosomal recessive trait, that is, for a child to develop a pathology, it is necessary that the HGD gene is damaged in both parents.
Back in 1925, scientists described a family in which there were 13 family members with a similar pathology.
If we talk about a healthy body, then homogentisic acid (alkapton) is completely broken down and converted into maleitacetoacetic acid, which turns into acetoacetic and fumaric acid. These acids play an important role in many biochemical cycles of the body. If a person has a mutated gene, alkapton accumulates in the body and causes a number of unpleasant symptoms and diseases.
Terminology
Phenylalanine is an amino acid that is involved in the formation of insulin, papain and melanin. It is necessary for the normal functioning of the central nervous system, helps to cope with depression. Although today it is still not clear how this substance acts in the body.
Tyrosine is an aromatic alpha amino acid that, like phenylalanine, is involved in catabolism. Amino acid is a completely intermediate decomposition product in the human body.
Clinical picture
To date, a number of characteristic signs of the disease are distinguished.
First of all, alkaptonuria is a darkening of the urine, which is noticeable even in infancy. Upon contact with oxygen, alkapton takes on a dark color. This symptom can lead to the development of pyelonephritis or urolithiasis, renal failure.
The next symptom characteristic of the disease is a grayish-bluish color of the skin. Most often manifested on the cartilage of the ears, in the armpits, in the groin and sinuses.
Excessive pigmentation can occur on the larynx, pancreas and thyroid gland, and other internal organs. You can notice a color change using endoscopic examination.
Symptoms of alkaptonuria appear on the musculoskeletal system. In particular, with damage to the spinal column, spondylosis of the thoracic or lumbar region is formed. The patient suffers not only from painful sensations, but mobility in the spinal column can be limited, up to complete immobilization. At first, the patient feels stiff while moving, then pains appear. Over time, the pain only intensifies. Some patients even experience a process of growth reduction. In places where the spinal column is affected, when probing, pain is not felt at all.
The disease affects the joints, with the further development of osteoarthrosis. Pathology affects large joints, in particular the shoulder, knee and hip joints. A swelling appears in the affected area, mobility is impaired, and constant pain is tormented.
Calcification is also possible, that is, deposition of calcium in articular bags or intervertebral discs. Pathology can cause the development of atherosclerosis, since alkapton can accumulate on the valves of the aortic valve.
Depending on the place where the alkapton accumulates, problems arise there. As mentioned earlier, first of all, in the place of accumulation of the substance, the surface darkens, acquiring a grayish-bluish tint.
Childhood symptoms
Alkaptonuria is, first of all, a genetic disease, therefore it is most often detected almost immediately at the birth of a baby. Usually the mother notices that the urine of the baby darkens after going outside. At the same time, dark spots remain on the diapers, which cannot be removed. Some babies have a darkening of the skin in the folds, up to compaction.
In cases where it is not possible to diagnose pathology in childhood, the main symptomatology is manifested from about 30 years of age. Joint problems most often occur at 35-40 years of age.
Forms
To date, there are only two forms of pathology. First of all - genetic, that is, directly related to the genetic mutation. If only one parent has a mutated gene, then the child will not develop the disease, and the accumulation of harmful substances in the body is also excluded.
Recent studies have shown that pathology can be acquired and occur against a background of vitamin C deficiency, however, after filling the deficiency, all signs and symptoms instantly disappear.
Diagnostic Principles
Diagnosis of the disease begins with a detailed history taking. The following methods are used to confirm or deny the presence of the disease:
- general urine analysis, which allows in the laboratory to detect darkening;
- biochemical analysis, which is designed to detect homogentizinic acid in the urine.
Other diagnostic methods are aimed at determining the degree of damage to various organs. In particular, radiography of the spine or joints can be performed to determine the degree of narrowing of the intervertebral fissures, the presence of free intraarticular bodies, whether there is calcification or osteophytes. If you find any problems for clarification, an ultrasound scan is performed.
Checking pigmentation inside the joints can be done using arthroscopy, and a study of synovial fluid is also performed. This technique allows you to determine the presence of an inflammatory process.
It is possible that in the presence of alkaptonuria, clinical recommendations will consist in performing an ultrasound of the kidneys or pyelography. Since pathology very often gives complications to the kidneys. In men, prostate ultrasound is performed in 99%.
With complaints of the heart, you will need to undergo an ultrasound of the aorta and heart muscle.
Depending on the results obtained, the therapist sends the patient to a specialized doctor.
Principles of Therapy
So, if phenylalanine is an irreplaceable amino acid, then a large amount of ascorbic acid is included in drug therapy of pathology. Up to 6 grams per day, every day. In this case, ascorbic acid will participate in the process of tyrosine decomposition. This, of course, is not a complete substitute for phenylalanine, but today there is no drug that could fully replace the missing enzymes. However, a number of doctors are of the opinion that in order to alleviate the symptoms and slow down the development of the disease, you should switch to a diet that is low in protein.
Other treatment methods are aimed only at reducing the symptoms of the disease. To reduce pain in the cartilage, joints and spinal column, non-steroidal anti-inflammatory drugs are used. For muscle relaxation in the spine, muscle relaxants are prescribed.
To improve metabolic processes in cartilage joints, chondroprotectors are used.
After removing the main pain, physical therapy and other physiotherapeutic procedures are very useful. In particular, radon baths give good results. The adoption of such baths is a comprehensive improvement of the whole organism. Mud therapy, ozokerite and paraffin baths are also recommended. It is also good to relieve muscle tension massage procedures.
Sometimes, patients whose joints are too damaged have to be replaced surgically with artificial ones to ensure a decent quality of life, that is, orthopedic surgery is performed. Surgical intervention is also indicated for damage to the heart valve.
It should be understood that alkaptonuria is a genetic disease, and it is impossible to completely get rid of it. All therapeutic measures are aimed at maintaining the body, relieving pain.
Forecast
It must be recognized that there is no specific treatment, so the prognosis in the presence of this type of pathology is unfavorable. No matter which organ is most affected, the disease will gradually develop and at some point everything will go to disability.
Preventive actions
It is impossible to take any measures to prevent the disease. The only thing that parents can do is pass a genetic examination before conceiving a child. Moreover, you should consult this doctor if alkaptonuria is diagnosed in at least one of the relatives.