What is Alcaptonuria?

Alcaptonuria is a hereditary disease caused by loss of the functions of homogentisic acid oxidase and characterized by a disorder of tyrosine metabolism and urinary excretion of a large amount of homogentisic acid. Using the example of alkaptonuria, Sir Archibald Garrod developed the concept of a metabolic unit.

Causes of Alcaptonuria

Alcaptonuria arises due to the mutation of the gene encoding the synthesis of homogenesis acid oxidase. This pathology is characterized by an autosomal recessive mode of inheritance. Alcaptonuria often sick men. The gene of the human homogynthinic acid oxidase (HGD) is located on the long arm of human chromosome 3 (3q 21-23).

Pathogenesis during Alcaptonuria

Under normal conditions, homogenesis acid – an intermediate product of the breakdown of tyrosine and phenylalanine – translates maleylacetoacetic acid, from which fumaric and acetoacetic acids ultimately form, which enter into other biochemical cycles. Due to a defect in the enzyme, this process is inhibited, and the remaining homogenesis acid in excess is converted by polyphenol oxidase into a quinone polyphenol (alkapton or benzoquinone acetate), which is excreted by the kidneys. Alcaptone, which is not completely excreted by urine, is deposited in cartilage and other connective tissue, causing their darkening and increased fragility. Most often, pigmentation of sclerae and ear cartilage appears.

Symptoms of Alcaptonuria

An early sign of Alcaptonuria is urine excretion in a child, which darkens rapidly when standing in air, is heated, alkalized. In the future may join urolithiasis, complicated by pyelonephritis. Signs of a lesion of the musculoskeletal system usually appear after 30 years. Characterized by predominant lesion of the large joints of the lower extremities: knee, hip. Rarely involved in the process of shoulder joints. Changes are characterized by secondary osteoarthritis. Pain of a mechanical nature is noted, often synovitis occurs that is resistant to treatment. The number of inflammatory cells in the synovial fluid is small. In many patients, rapid progression of destructive changes in the joint cartilage is noted. Sometimes the period extending from the debut of the articular syndrome to the development of pronounced changes that require joint arthroplasty may be 2-3 years. Excessive deposition of homogentesic acid in ligaments, tendons and their membranes is often noted, leading in some cases to the development of local inflammatory changes and calcification. Often affects the spine. Main symptoms: pain and limitation of movement mainly in the lumbar region, less often in the thoracic and cervical spine. Radiographs reveal changes characteristic of common osteochondrosis, as well as calcification of intervertebral discs, which is the hallmark of occlusion. Perhaps as an isolated lesion of the spine, and the simultaneous involvement of large joints. Clinical signs of spinal column damage in Alcaptonuria may resemble ankylosing spondylitis. When examining such patients there is a significant limitation of spinal movements. In case of occlusion, X-ray changes of the sacroiliac joints (osteoarthrosis) may occur, which are somewhat similar to those of sacroiliitis. The damage to the cartilage of the auricles occurs in almost all patients with Alcaptonuria in the advanced stage of the disease. At the same time, the color of the auricles changes: it can vary from blue to gray, the color can be both intense and slightly noticeable. The elasticity of the auricles also changes: on palpation, they become more dense and rigid. Rarely changes skin color in the area of ​​nasolabial folds, underarms, palms. These changes are asymptomatic. Very often, patients with Alcaptonuria develop pigmentation of the sclera, which is associated with the deposition of deposits of homogentesic acid in them. The intensity of such deposits may be different. These changes usually do not bother patients, but are among the signs of this disease that have important diagnostic value. In Alcaptonuria, approximately 20% of patients develop changes in the aortic valve (rarely – mitral): calcification of the cusps, fibrous ring, and ascending aorta. These changes can be significant, leading to significant hemodynamic disturbances, which in some cases require surgical treatment (valve replacement). There is evidence of the development of coronary artery calcification. Calculous prostatitis is often found in Alcaptonuria. Usually it is of little or asymptomatic, it is detected by ultrasound or X-ray examination.

Diagnosis of Alcaptonuria

The most informative method for the diagnosis of alcaptonuria is a method for the quantitative determination of homogenesis acid and benzochinoacetic acid in the urine. Enzymatic spectrophotometry or liquid chromatography is used for this. A simpler, but less accurate way to detect this disease is to assess the color of urine 12-24 hours after it is exposed to air. In this case, alkapton oxidation occurs, which leads to a change in the color of urine (it becomes brown or black). These changes occur only at alkaline pH values ​​of urine, therefore, when an acid reaction of the urine is necessary alkalization. In some cases, the diagnosis of “Alcaptonuria” can be made by identifying the characteristic pigmentation of cartilage during arthroscopy, the synovial membrane during microscopic examination, or heart valves during their prosthetics. It is important to distinguish between genetic alkaptonuria and alkaptonuria in hypovitaminosis C. The latter disappears after the administration of an adequate dose of ascorbic acid. Alcaptonuria should be distinguished from hematuria, hemoglobinuria, melaninuria, porphyria.

Alcaptonuria Treatment

There is no radical treatment, symptomatic therapy and large doses of ascorbic acid are used.

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