COMPARATIVE CHARACTERISTICS OF THE MECHANISMS OF BILIARY TRACT DYSFUNCTION DEVELOPMENT IN CHILDREN WITH CONNECTIVE TISSUE DYSPLASIA

SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 236 COMPARATIVE CHARACTERISTICS OF THE MECHANISMS OF BILIARY TRACT DYSFUNCTION DEVELOPMENT IN CHILDREN WITH CONNECTIVE TISSUE DYSPLASIA N.A. Khodzhaeva Assistant, Department of Faculty Pediatrics, Tashkent State Medical University https://doi.org/10.5281/zenodo.17862063 Abstract. Biliary system diseases remain a significant medical and social problem worldwide, as evidenced by a steady increase in their prevalence and DALYs indicators according to GBD data over recent decades. Biliary dysfunctions occupy an important place among pediatric gastroenterological disorders, with their frequency varying considerably depending on age. Despite their high prevalence, the mechanisms underlying biliary dysfunction in the context of undifferentiated connective tissue dysplasia remain insufficiently studied, emphasizing the need for further research. Particular attention should be given to identifying pathogenetic links between these conditions and assessing their long-term consequences. Keywords: connective tissue dysplasia, biliary tract dysfunction. Introduction Diseases of the biliary system (BSD) remain an important medical and social problem worldwide, particularly in economically developed countries. According to the Global Burden of Disease (GBD) data, from 1990 to 2019 the number of BSD cases increased from 127 to 193 million, and the DALYs indicator rose from 4.6 to 6.35 million [1,2,6]. Biliary dysfunctions occupy a significant place among gastroenterological diseases in children. The prevalence of some forms ranges from isolated cases to several tens of percent, depending on age. Insufficient study of the mechanisms of biliary dysfunction against the background of connective tissue dysplasia (CTD) at an early age determines the need for further research, especially aimed at identifying a pathogenetic connection between these conditions. The long-term consequences of these disorders also remain insufficiently understood. The clinical and pathological features of biliary tract dysfunction in children are shaped by age-related anatomical and physiological changes, characteristics of the body's reactivity, and the state of connective tissue. In children with connective tissue insufficiency, biliary dysfunctions are often accompanied by a history of infectious-inflammatory and digestive diseases, which accounts for the diversity of clinical manifestations [3,4,7]. The variability of symptoms is determined by the combined effects of various factors: etiological, constitutional, hereditary, and others. Although the role of these factors has been studied to a considerable extent, the influence of their combinations and their distribution across clinical and laboratory variants of biliary pathology in children remain insufficiently explored. The course of the disease largely depends on the development of inter-organ disorders and combined lesions of different body systems. The pathological process often affects the organs of the gastrointestinal tract, which may lead to complications, reduced quality of life, and—in severe cases—disability. Despite numerous clinical descriptions in the literature, clear diagnostic criteria for biliary tract dysfunction in connective tissue dysplasia and algorithms for predicting its course are still lacking. Analysis of current research on connective tissue dysplasia in children of different age groups shows that at SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 237 present there is no simple and effective algorithm for detecting biliary tract abnormalities against the background of connective tissue insufficiency. In this regard, the objective of the present study was formulated. Aim of the Study To investigate the pathogenetic mechanisms and conduct a comparative analysis of biliary tract dysfunction in combination with connective tissue dysplasia. Materials and Methods A total of 159 children aged 3–16 years were examined. Of the total number of patients observed, 59.7% (95 children) were preschoolers (3–6 years old), of whom 55.7% (53) were boys and 44.2% (42) were girls. Children of primary school age (7–11 years) accounted for 30.1% (49 children): 53% (26) boys and 47% (23) girls. Children of senior school age (12–16 years) represented 9.4% (15 children): 26.6% (4) boys and 73.3% (11) girls. Overall, despite gender differences, the incidence of biliary tract disorders was higher among boys, who made up 52.2% (83 children), compared to girls at 47.8% (76 children). However, with increasing age, this pattern changed: in senior school-aged children, the incidence in girls was three times higher—73.3% (11 children), compared to boys at only 26.6% (4 children). Out of the total 159 children (100%), boys accounted for 52.2% (83), and girls for 47.8% (76). All children were divided into two groups:  The main group, which included 121 children (76%) with biliary tract pathology combined with connective tissue dysplasia;  The comparison group, consisting of 38 children (24%) with biliary tract dysfunction without connective tissue dysplasia. Among the laboratory methods, the blood level of hydroxyproline was analyzed as a marker of connective tissue metabolism, as well as the concentrations of macroelements involved in collagen synthesis (Mg, Ca). Results of the Study In our study, hydroxyproline levels in children of the main group were as follows:  Preschool age: 26.14 ± 0.90 µg/mL (p < 0.05),  Primary school age: 22.82 ± 1.03 µg/mL,  Senior school age: 24.67 ± 2.06 µg/mL. In the comparison group, the hydroxyproline level was slightly elevated across all age groups:  24.19 ± 0.99 µg/mL,  22.52 ± 1.31 µg/mL,  23.01 ± 2.86 µg/mL. In healthy children, the hydroxyproline level was within normal limits:  17.99 ± 1.27 µg/mL,  18.26 ± 1.11 µg/mL,  18.68 ± 1.18 µg/mL. In both the main and comparison groups, hydroxyproline levels were significantly higher compared to healthy children. It was also found that the highest levels were observed in preschoolaged children. A similar pattern was noted in the comparison group (Diagram 1). SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 238 The Results of the Analyses The results of the analyses obtained in our study indicate that both examined groups— children with biliary tract dysfunction (BTD) combined with connective tissue dysplasia (CTD), and children with BTD without CTD—showed changes in blood macroelement levels. When comparing the magnesium (Mg) level in blood plasma among children of different age groups (3– 6 years, 7–11 years, 12–16 years) with BTD and CTD, a significant decrease was observed (0.58 ± 0.01 mmol/L, 0.56 ± 0.02 mmol/L, 0.55 ± 0.03 mmol/L, respectively). However, in the comparison group (BTD without CTD), the Mg content in the blood remained within the normal range in all three age groups (0.71 ± 0.03 mmol/L, 0.79 ± 0.02 mmol/L, 0.80 ± 0.03 mmol/L). According to many researchers and experts, the blood Mg level is stable and changes only in cases of pronounced deficiency. There is evidence that when Mg is deficient, manganese can substitute for it in the active center of one of the enzymes involved in collagen synthesis and osteogenesis, thereby performing similar functions. Hypomagnesemia is widespread among children and is especially characteristic of patients with CTD combined with BTD. A similar age-related pattern was observed regarding calcium (Ca) levels in the main group of children. The Ca level in blood plasma among all age groups (3–6 years, 7–11 years, 12–16 years) with BTD and CTD showed no significant differences (2.00 ± 0.02 mmol/L, 2.00 ± 0.02 mmol/L, 2.01 ± 0.03 mmol/L), but remained low across all three age groups compared to the values in the comparison group (2.24 ± 0.11 mmol/L, 2.63 ± 0.12 mmol/L, 2.54 ± 0.12 mmol/L) and healthy children (2.67 ± 0.12 mmol/L, 2.72 ± 0.16 mmol/L, 2.54 ± 0.13 mmol/L). It has been previously proven that insufficient Ca intake leads to disturbances in the metabolism of various microelements; therefore, their participation in collagen formation, bone tissue development, and other vital functions is possible only with an adequate supply of calcium to the body (Diagram 2). 26 23 25 24 22.5 23 17 18 18 0 10 20 30 40 50 60 70 80 3 -6 years 7 -11 years 12-16 years In healthy children BTD without CTD BTD with CTD SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 239 Fig. 2. Comparative Assessment of Blood Macroelements in the Examined Children Regardless of Age As is well known from the research of many scientists, when there is a deficiency of macroelements in the body, the synthesis of certain enzymes is disrupted. These enzymes actively participate in the formation of major connective tissue proteins, such as collagen, as well as in bone tissue development. Thus, it can be stated that, along with hereditary predisposition, an imbalance in the body’s microelement status may also be one of the causes of connective tissue disorders, leading to connective tissue dysplasia. Conclusions In children with biliary tract dysfunction—both with and without connective tissue dysplasia—the level of hydroxyproline in the blood is significantly higher than in healthy peers, with the highest values observed in preschool-aged children. This indicates increased collagen metabolism in this group of children. Hydroxyproline is present exclusively in collagen. During protein translation in ribosomes, this amino acid does not enter the polypeptide chain directly; instead, it is formed through post-translational modifications that precede collagen formation. In this process, proline already incorporated into the polypeptide chain undergoes hydroxylation. Therefore, the hydroxyproline detected in the blood always represents a product of collagen catabolism and contributes to the elasticity of connective tissue. An increase in hydroxyproline reflects disturbances specifically in collagen rather than in the general protein fraction. In children with biliary tract dysfunction combined with connective tissue dysplasia, lower levels of magnesium and calcium are observed compared to children with BTD without CTD. This indicates a high frequency of hypomagnesemia and calcium deficiency in this group, which may disrupt microelement metabolism and affect collagen synthesis and bone tissue formation. Thus, the levels of Ca and Mg in blood plasma tend to decrease. 0 0.5 1 1.5 2 2.5 3 BTD with CTD BTD without CTD in healthy children 2 2.54 2.67 0.56 0.75 0.85 Са Mg SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 240 According to the study results, an imbalance of macroelements against the background of biliary tract pathology is one of the pathogenetic factors contributing to the growth and development of connective tissue dysplasia in children of various ages. REFERENCES 1. Ibodullaeva S. Sh., Muratkhojaeva A., Dauksh I. Influence of gallbladder anomalies on the development of biliary tract pathology in children with digestive system disorders. Eurasian Bulletin of Pediatrics, 2019; 3(3): 143–149. 2. Yuryeva E. A., Dlin V., Vozdvizhenskaya E. S., Sukhorukov V. S., Semyachkina A. N., Kharabadze M. N. 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