Alkaptonuriya – genetically caused metabolism violation which is characterized by congenital deficiency of enzyme of a gomogentizinaza and leading to incomplete splitting of gomogentizinovy acid, its ekskretion with urine and to adjournment of this metabolite in fabrics (skin, articulate cartilages, sinews, skler, etc.). Signs of an alkaptonuriya appear in the childhood and include release of the urine which is quickly darkening on air, pigmentation of skin and a skler, osteoarthrosis, , hoarseness of a voice, a dysphagy etc. The diagnosis of an alkaptonuriya is established taking into account clinical manifestations and laboratory tests (a biochemical research of urine, the analysis of sinovialny liquid), a X-ray analysis, an arthroscopy. Treatment of an alkaptonuriya has symptomatic character (a dietotherapy, vitamin C, hondroprotektor, NPVS, a balneofizioterapiya); if necessary prosthetics of joints or valves of heart is carried out.
Alkaptonuriya (a gomogentizinovy atsiduriya, hereditary ) – hereditary pathology of a metabolism which cornerstone the violation of metabolism of a tirozin leading to excess formation of an intermediate metabolite - gomogentizinovy acid is. Accumulation in an organism of gomogentizinovy acid and its allocation with urine also define a current of the simptomokompleks known as an alkaptonuriya. As the disease is followed by polysystem defeat, it is of practical interest to a number of medical disciplines: rheumatology, dermatology, orthopedics, urology, a heart surgery, genetics, etc. Alkaptonuriya meets seldom, frequency of 1:250 thousand-1:1 million people in the world. More pathology is widespread among male population of Dominican Republic, Germany, the Czech Republic, Slovakia, India, the USA.
Alkaptonuriya is among genetically caused enzimopatiya inherited on autosomno-recessive type i.e. for development of clinical displays of a disease the child has to receive from each of parents according to one copy of a mutant gene. At an alkaptonuriya of a mutation mention the gene of an oxidase of gomogentizinovy acid (HGD) localized on a long shoulder 3 chromosomes (3q 21-23). Gomogentizinaza enzyme reproduction (a gomogentizinovy oxidase) which participates in splitting of a tirozin and phenylalanine is as a result broken.
The gomogentizinovy acid which is an intermediate metabolite of exchange of a tirozin and phenylalanine under the influence of a gomogentizinaza is normal it is transformed to maleilatsetouksusny acid and further it is split to acetoacetic and fumaric acids which then participate in the subsequent biochemical cycles. At an alkaptonuriya, in the conditions of congenital deficiency of enzyme, gomogentizinovy acid is not exposed to further metabolism, and turns into hinonovy polyphenols (a pigment ) which collect in connecting fabrics and in large numbers ekskretirutsya with urine (to 4-8 g a day).
Alkaptonuriya is characterized by the following main simptomokompleks: gomogentizinovy atsiduriya, okhronozy and artropatiya. These signs arise at different times: coloring of urine exists since the birth, pigmentation of fabrics becomes expressed by 30 years, damage of joints develops on the fourth decade of life.
Early signs of an alkaptonuriya can be noticed at early children's age: on wet diapers of the child there are dark stains from urine which cannot be washed. Because of a large amount of gomogentizinovy acid collected urine when upholding also quickly gains dark-brown color. Further from urinogenital bodies pyelonephritis, an urolithic disease, kalkulezny prostatitis quite often develop.
The skin syndrome at an alkaptonuriya is characterized by emergence of gray-brown pigmentation on a face (in the field of a nose back, around lips and eyes), on a neck, palms, a stomach, axillary and inguinal area. Consolidation and gray-blue coloring of auricles, pigmentation skler and conjunctivas is a typical sign of an alkaptonuriya. Diffusion adjournment of a pigment is noted in throat cartilages that is followed by hoarseness of a voice, short wind, a dysphagy and pain when swallowing. Over time the kaltsifikation of an aorta and valves of heart develops, atherosclerosis, the acquired aortal and mitralny defects are a consequence of what. At severe forms of an alkaptonuriya adjournment of a pigment can meet in a thyroid gland, adrenal glands, testicles, a pancreas, a spleen.
Defeat of musculoskeletal system at an alkaptonuriya, affects, mainly, large joints of the lower extremities and a backbone. Before all change as the deforming spondilez develop in lumbar, then in chest department of a backbone. At the same time the smoothness of a lumbar lordoz, pain and constraint gradually accrues at the movements, up to total loss of mobility in the struck departments of a backbone. After damage of a backbone symptoms of the deforming osteoarthrosis of knee, shoulder and coxofemoral joints appear. Artralgiya, a swelling of joints (jet sinovit), a krepitation, mobility, development of sgibatelny contractures are characteristic. Quite often at an alkaptonuriya are surprised sacral joints and a lonny joint.
Diagnostics of an alkaptonuriya
Most often the alkaptonuriya is diagnosed at early children's age, however in some cases can come to light only in process of development of full simptomokompleks. Instructions on release of the urine darkening on air are important; existence of pigmentation and consolidation of skin; the progressing damage of a backbone and joints. The correct diagnosis is promoted tool (radiological, ultrasonic, endoscopic) also by laboratory inspection. For the purpose of assessment of the violations accompanying an alkaptonuriya patients need consultation of the rheumatologist, orthopedist, dermatologist, urologist, nephrologist, cardiologist, ophthalmologist.
When carrying out a X-ray analysis of a backbone signs of a hondrokaltsinoz of intervertebral disks and an osteosclerosis of bodies of vertebras, narrowing of intervertebral cracks come to light. Data of ultrasonography and a X-ray analysis of large joints are characterized by narrowing of articulate cracks, an osteosclerosis, existence of osteofit and free intra articulate bodies, an ossifikation of cartilages and periartikulyarny fabrics. The diagnostic arthroscopy of knee and coxofemoral joints at an alkaptonuriya allows to find characteristic pigmentation of a cartilage. Stones in kidneys and a prostate come to light during a piyelografiya, ultrasonography of kidneys and a prostate gland. The condition of valves of heart and vessels is specified when carrying out EhoKG, aorta UZDG. When carrying out a laringoskopiya it is possible to see dark coloring of cartilages of a throat.
Pathogenetic diagnostics of an alkaptonuriya provides a biochemical research of urine by means of a method of an enzymatic spektrofotometriya or a liquid chromatography and definition in it gomogentizinovy and benzokhinouksusny acids. Assessment of color of urine allows to notice its considerable darkening at stay on air, warming up and alkalifying. The research of sinovialny liquid in which there are no inflammation signs can give certain help, but particles of an okhronotichesky pigment contain. Changes, specific to an alkaptonuriya, are found in the sinovialny cover received by means of a joint biopsy.
Differential diagnostics of an alkaptonuriya needs to be carried out with osteochondrosis, Bekhterev's disease, a porfiriya, amiloidozy, argirozy, lipoproteinozy, etc. The genetic form of a disease should be distinguished from the symptomatic alkaptonuriya caused by hypovitaminosis With – the last disappears after purpose of high doses of ascorbic acid.
Treatment of an alkaptonuriya
Etiopatogenetichesky therapy of a genetic alkaptonuriya is not developed today. For prevention of excess formation of gomogentizinovy acid some authors point to expediency of observance of a reduced-protein diet. For the purpose of improvement of metabolism of a tirozin at an alkaptonuriya vitamin C reception is shown. Generally medicamentous therapy of an alkaptonuriya has symptomatic character and includes reception of nonsteroid resolvents, spazmolitik, hondroprotektor; intra articulate introduction of a hydrocortisone, hyaluronic acid. Balneofizioterapevtichesky procedures (radonic bathtubs, mud cure, paraffin applications), massage, physiotherapy exercises have positive effect.
At considerable deformation of joints the issue of carrying out ortopedokhirurgichesky correction – endoprosthesis replacement of knee, coxofemoral or shoulder joints is resolved. In case of development of a gemodinamicheska of significant defeat of valves of heart prosthetics of the mitralny or aortal valve is carried out.
Forecast of an alkaptonuriya
Forecast for treatment of an alkaptonuriya adverse. The disease has the chronic progressing current with development of irreversible changes in an organism. An outcome of an alkaptonuriya is the resistant invalidization of the patient. The genetic nature of pathology does not allow to speak about a possibility of specific prevention. For the forecast of development of an alkaptonuriya in posterity consultation of the geneticist is recommended.