Журнал «Здоровье ребенка» 2 (61) 2015
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Location undifferentiated connective tissue dysplasia in diseases of childhood.
Авторы: Lukyanenko N.S.(1), Petritsa N. A.(1), Kens K.A.(2)
(1) — State Institutions «Institute of Hereditary Diseases of National Academy of Medical Sciences of Ukraine»
(2) — Danylo Halytsky Lviv National Medical University, Department of Pediatric Surgery.
Рубрики: Педиатрия/Неонатология
Разделы: Клинические исследования
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Introduction.
Recently, the scientific attention has been drawn to the increasing number of microanomalies and morphogenetic changes in the different organs, triggered by the peculiarities of the connective tissue. These changes are expressed by certain phenotypic displays and are interpreted as undifferentiated connective tissue dysplasia (UCTD).
Objective. To systematize literature data concerning the problem of congenital urinary tract defects in children associated with undifferentiated connective tissue dysplasia.
Discussion. Connective tissue presence in all of the organs in human body, common genesis, morphology and function complexity determine active participation of its main elements in the formation and development of different types of pathologies, causing dysplastic changes in various organs and systems. This type of pathology is strongly connected with genetic mutations and multifactorial external influence during pregnancy.
Connective tissue dysplasia – is a genetically determined condition, which leads to defection in connective tissue development during embryonic and postnatal periods. It is characterized by the defection in connective tissue development, consequently leads to homeostasis interruption on the tissue, organic and organismic level and displays in the form of different morphological and functional deviations of the visceral and locomotors organs with progressive course.
Accordingly, UCTD is a genetic heterogenic group of disorders of multifactorial origin with progressive course, and is based on the synthesis, disintegration or morphogenesis of the components of extracellular matrix. This pathology appears in the period of early embryogenesis or in postnatal period and is caused by adverse factors of the environment and can manifest on the different stages of life.
According to the data of different authors the frequency of UCTD diagnosis is sufficient and estimates nearly 26-80%, depending on the group of the patients that are being researched.
Taking Zemtsovskyy E.V. data into consideration, the frequency of this disorder among youth (up till 25 years) estimates till 80%, however, in case when more strict criteria are implemented (six and more external markers) it can be narrowed to 20-25%, therefore the clinical value of such results is much higher.
The etiopathology of congenital imperfection of the connective tissue is not studied enough; however the numerous researches demonstrate that clinical displays of UCTD are caused by the collagen structures anomalies. 20 genetic types of the collagen, which are coded by nearly 50 genes, have been described.
Tissue ontogenesis is closely related to the collagen synthesis anomalies and fibrillogenesis, as well with the changes of its biodegradation, enzyme patologies, fibronectin defects, elastin, glycoproteins, proteoglycans and with the enzymes cofactor deficit (Cu, Zn, Mg and ascorbic acid etc), that take part in the transverse covalent connections formation, that are essential for collagen structures stabilization.
Genetic defects of collagen synthesis lead to the reduction of transverse connections and the elevation of its soluble fractions. Consequently, children with congenital collagen synthesis defect tend to have elevated levels of oxoproline in daily urine, which expression correlates with the pathological process severity.
Congenital defects of fibrylogenesis, which are coordinated by collagen type IV and are coded by 13-chromosome, contribute to the renal and urinary tract pathology formation.
According to Insel T.N., the elevated levels of hydroxyproline, lysine, and proline in the blood serum can be considered as indirect markers of collagen hypercatabolism, which correlate with the oxyprolyn elevation in the daily urine. The intracellular matrix catabolism can be interpreted by the levels of GAG excretion, which are usually elevated in the blood serum of the children with different types of connective tissue pathology.
Molecular methods of the evaluation of genetic mutations and presence of antigens of histocompatibility are considered to be the most modern, up to date and perspective. The elevated levels of HLA representatives – A28, B35, Cw5, Cw52, and decreased levels of – A2, B18, Cw3 are determined on the leukocyte membranes in children with congenital connective tissue pathology defects. Several scientific researches revealed the prevalence of HLA-B12, -B18, -B35 in patients with different types of nephropathies.
The evaluation of the activeness of the proteolytic enzymes – collagenase and elastase in the blood serum, elastase inhibitors, tissue metalloproteinases and its inhibitors could be considered to be effective and perspective methodologies. Determination of the level of Mg, Ca, Cu, ascorbic acid, that indicate the connective tissue pathology could be considered as a valuable accessory biochemical diagnostic method of UCTD in children.
Conclusion. Current literature analysis allows us to conclude, that there is no effective algorithm of UCTD diagnosis, in particular of the renal expression in neonates and toddlers. There are no clear recommendations regarding the future treatment of such pathologies as well.
There is some literature data regarding the Mg and Cu supplementation and its repetitive courses in addition with the hand massage, corrective gymnastics and swimming in the aspect of formation of severe complications involving dysplastic changes organs prophylactics. Considering the progressive course of UCTD, early diagnosis in the neonatal and in early childhood periods could be useful for timely metabolic correction of the connective tissue dysfunction in order to stop the progression of the disease.
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