Alcaptonuria

Alcaptonuria occurs due to mutations in the gene encoding the synthesis of homogenesesinic acid oxidase . This pathology is characterized by an autosomal recessive type of inheritance. Alkaptonuria often affects men. The human homogetinzinic acid oxidase gene (HGD) is located on the long arm 3 of the human chromosome (3q 21-23).

Under normal conditions, homogentisic acid , an intermediate decomposition product of tyrosine and phenylalanine, is converted to maleylacetoacetic acid , from which ultimately fumaric and acetoacetic acids are formed, which enter other biochemical cycles. Due to an enzyme defect, this process is inhibited, and the remaining homogentizinic acid is converted by polyphenol oxidase to quinone polyphenol ( alkapton or benzoquinone acetate ), which is excreted by the kidneys . The alkapton that is not completely excreted by urine is deposited in the cartilage and other connective tissue , causing their darkening and increased fragility . Most often, pigmentation of the sclera and ear cartilage appears first.

An early sign of alkaptonuria is the release of urine in a child, which quickly darkens when standing in the air, warming, alkalizing. In the future, urolithiasis , complicated by pyelonephritis , can join. Signs of damage to the musculoskeletal system usually appear after 30 years. The predominant lesion of large joints of the lower extremities is characteristic: knee, hip. Less commonly, shoulder joints are involved. Changes are characterized by secondary osteoarthrosis. There are mechanical pains, often there is synovitis , resistant to treatment. The number of inflammatory cells in the synovial fluid is small. Many patients have a rapid progression of destructive changes in the cartilage of the joints. Sometimes the period from the debut of articular syndrome to the development of pronounced changes requiring joint replacement can be 2-3 years. Excessive deposition of homogenesesic acid in ligaments, tendons and their membranes is often noted, leading in some cases to the development of local inflammatory changes and calcification. The spine is often affected. The main symptoms: pain and restriction of movements mainly in the lumbar, less often in the thoracic and cervical spine. Radiographs reveal changes characteristic of common osteochondrosis, as well as calcification of the intervertebral discs, which is a hallmark of ochronosis. It is possible both an isolated lesion of the spine and the simultaneous involvement of large joints. Clinical signs of damage to the spinal column in alkaptonuria may resemble ankylosing spondylitis. When examining such patients, there is a significant restriction of the movements of the spine. With ochronic disease, x-ray changes in the sacroiliac joints (osteoarthritis) can occur, partly similar to those with sacroiliitis. Damage to the cartilage of the auricles occurs in almost all patients with alkaptonuria 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: upon palpation, they become more dense and rigid. Less often, skin color changes in the area of ​​nasolabial folds, axillary hollows, palms. These changes are asymptomatic. Very often, patients with alkaptonuria develop scleral pigmentation, which is associated with the deposition of deposits of homogenesinic acid in them. The intensity of such deposits can be different. These changes usually do not bother patients, but are some of the signs of this disease that have important diagnostic value. With alkaptonuria, approximately 20% of patients develop changes in the aortic valve (rarely the mitral valve): calcification of the valves, fibrous ring, and also the ascending aorta. These changes can be significant, leading to significant hemodynamic disturbances, requiring surgical treatment in some cases (valve prosthetics). There is evidence of the development of calcification of coronary arteries. Calculous prostatitis is often found in alkaptonuria. Usually it proceeds slightly or asymptomatically, detected by ultrasound or radiological examination.

The most informative method for the diagnosis of alkaptonuria is the method for the quantitative determination of homogentisic acid and benzoquinoacetic acid in urine. Enzymatic spectrophotometry or liquid chromatography is used for this. A simpler, but less accurate way to detect this disease is to evaluate the color of urine 12-24 hours after being in the air. In this case, alkapton is oxidized, which leads to a change in the color of urine (becomes brown or black). These changes occur only at alkaline pH values ​​of urine, therefore, with an acidic reaction of urine, alkalization is necessary. In some cases, the diagnosis of "alkaptonuria" can be established by identifying the characteristic pigmentation of the 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 appointment of an adequate dose of ascorbic acid. Alcaptonuria should be distinguished from hematuria , hemoglobinuria , melaninuria , porphyria .

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

This disease is transmitted genetically in an autosomal recessive manner. Parents of a person with an autosomal recessive disease are carriers of one copy of each of the mutation genes, but usually they have no signs of the disease.

• Da-med.ru ::: Alkaptonuria (Ochronoz)