Problems of Radiation Medicine and Radiobiology

V. G. Bebeshko, K. M. Bruslova, T. T. Volodina, L. O. Lyashenko, N. M. Tsvetkova, I. V. Trychlib,
T. O. Chernysh, V. G. Boyarskiy, L. O. Gonchar, N. V. Kavardakova

State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine», 53 Yuriia Illienka str., Kyiv, 04050, Ukraine

FEATURES OF CLINICAL SYMPTOMS AND SIGNS, HEMATOLOGICAL AND BIOCHEMICAL PARAMETERS IN CHILDREN WITH JOINT HYPERMOBILITY IN A LATE PERIOD UPON THE CHORNOBYL NPP ACCIDENT

Objective. establishing the types and frequency of disembriogenetic stigma in children with joint hypermobility given the clinical and laboratory features, genetic component and endocrine regulation of these disorders in a late period upon the accident.
Materials and methods. Children (n = 109) inhabiting the radiologically contaminated territories and having the connective tissue dysplasia (CTD) signs were involved in the study. Diseases in family history, ossalgia complaints, fractures in a personal history, bone disembriogenetic stigma, joint hypermobility, type of somatic diseases, blood serum biochemical parameters (namely calcium, alkaline phosphatase, total protein, cholesterol, creatinine, iron, ferritin content), serum cortisol, free thyroxine, pituitary thyroid-stimulating hormone (TSH) levels, free amino acid composition in urine and radiation dose were considered.
Results. Radiation doses in children having the CTD ranged from (0.37 ± 0.11) mSv to (0.56 ± 0.10) mSv with no difference from that in those without CTD. Joint hypermobility (JHM) correlated with cancer in family history (rs = 0.53) and lower extremity varicose vein disease (rs = 0.40) (p < 0.05). Incidence of ossalgia, easy fatigability, and bone fractures was higher in children with CTD. Anomalies of the dentofacial system were first in line (38.5 %) in these children. Proportion of children with grade II JHM and platypodia was lower (rs = 0.42), but with lower extremity deformations was higher (rs = 0.68) (p < 0.05) vs. in the control group. Iron and ferritin deficiencies both with lymphocytosis were more common in children with CTD than in the comparison group (p < 0.05). The increased content of oxyproline, lysine, proline both with glycine deficiency were detected in children having the CTD, i.e. an imbalance of amino acids from the collagen content was observed featuring a predominance of catabolic processes over anabolic ones. There was a direct correlation between the TSH level and the JHM grade (rs = 0.49), although the values of hormone concentration in these children did not exceed the reference range (maximum values were 3.3 μIU/ml).
Conclusions. The revealed abnormalities in amino acid content, ferrokinetics, and thyroid function indices can affect the collagen formation, organic matrix structure of bone tissue and significantly deregulate the hematopoiesis. The later can underlie the pathways of haematologic malignancy development.
Key words: children, connective tissue dysplasia, joint hypermobility, disembriogenetic stigma, amino acids, iron, endocrine regulation, radiation dose.

Problems of Radiation Medicine and Radiobiology.
2019;24:322-334. doi: 10.33145/2304-8336-2019-24-322-334

full text

1. Marushko YuV. [Joint hypermobility syndrome in children]. Dytiachyi Likar. 2012;(6):40-4. Ukrainian.

2. Kumar B, Lenert P. Joint hypermobility syndrome: recognizing a commonly over-looked cause of chronic pain. Am J Med. 2017(130)6:640-7. DOI: https://doi.org/10.1016/j.amjmed.2017.02.013.

3. Kadurina TI, Abbakumova LN. [Assessment of the severity of undifferentiated connective tissue dysplasia in children]. Meditsinskyi Vestnik Severnogo Kavkaza. 2008;(2):15-20. Russian.

4. Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A. A framework for the classification of joint hypermobility and related conditions. Am J Med Genet C Semin Med Genet. 2017;175(1):148-57. DOI: https://doi.org/10.1002/ajmg.c.31539.

5. Lehman PJ, Carl RL. Growing pains. Sports Health. 2017;9(2):132-38. DOI: https://doi.org/10.1177/1941738117692533.

6. Pochinok TV, Veselova TV. [The state of peroxidation of proteins and lipids in non-differentiated dysplasia of connective tissue in children]. Semeinaya Meditsina. 2013;(4):170-1. Ukrainian.

7. Bebeshko VG, Bruslova KM, Panchenko LM, et al. [Interrelation between functional activity of bone marrow stromal fibroblasts, myelogram and prognosis of relapse of acute leukemia in children]. Collection of scientific papers of the P.L. Shupyk Memorial National Medical of Postgraduate Education. Kyiv. 2016;(25, book 2):83-7. Ukrainian.

8. Zou Y, Donkervoort S, Salo AM, Foley AR, Barnes AM, Hu Y, et al. P4HA1 mutations cause a unique congenital disorder of connective tissue involving tendon. bone. muscle and the eye. Hum Mol Genet. 2017;(26)12:2207-17. DOI: https://doi.org/10.1093/hmg/ddx110.

9. D'Amours G, Lopes F, Gauthier J, Saillour V, Nassif C, Wynn R, et al. Refining the phenotype associated with biallelic DNAJC21 mutations. Clin Genet. 2018;(94)2:252-8. DOI: https://doi.org/10.1111/cge.13370.

10. Likhtarev IA, editor. [1997 retrospective and projected radiation doses in population and general-dosimetry passportization of the settlements in Ukraine subject to radioactive contamination as a result of the Chornobyl accident. Summarized data for 1986–1997 period]. Collection Boook #7. Kyiv: MH of Ukraine; 1998. 155 p. Ukrainian.

11. Beighton P, Solomon L, Soskolne CL. Articular mobility in an African population. Ann Rheum Dis. 1973;32(5):413-8. DOI: 10.1136/ard.32.5.413.

12. Li P, Wu G. Roles of dietary glycine, proline and hydroxyproline in collagen synthesis and animal growth. Amino Acids. 2018 Jan; 50(1):29-38. DOI: https://doi.org/10.1007/s00726-017-2490-6.