Features of the somatic status of a patient with type II Crigler–Najjar syndrome. A clinical case in the practice of a pediatrician
Abstract
Introduction. Crigler–Najjar syndrome is characterized by a genetically determined disorder of transformation of bilirubin fractions in hepatocytes due to insufficient (type II) or complete (type I) absence of the enzyme uridine diphosphate glucuronidase-1. The syndrome has variable expressivity, and the degree of decrease in enzyme activity and clinical manifestations vary among patients; with an increase in unconjugated hyperbilirubinemia in the blood, jaundice is observed with the formation of bilirubin encephalopathy. The diagnosis is confirmed by detecting mutations in both copies of the UGT1A1 gene. Gene therapy for Crigler–Najjar syndrome type II is emerging as an attractive therapeutic approach, allowing patients to replace liver transplantation with an alternative treatment option. This tactic will help patients improve their prognosis for the quality and length of their lives. The aim of the study is to present a case report of type II Crigler–Najjar syndrome, rarely encountered in pediatric practice, diagnostic features and potential for implementing new therapeutic technologies. Basic provisions. The article describes a clinical case of type II Crigler–Najjar syndrome manifesting in the neonatal period in one of a pair of twins. The stages of the diagnostic work-up are outlined, and the results of molecular genetic testing are analyzed. The challenges of managing the child in outpatient settings due to the limited effectiveness of the current symptomatic treatment protocol are discussed, along with the prospects for applying modern genetically engineered therapeutic technologies. Conclusion. The diagnosis of Crigler–Najjar syndrome type II was established after conducting a molecular genetic study. The tactics of patient supervision by a district pediatrician and doctors of narrow specialties require the development of unified protocols for monitoring and pathogenetic treatment that improve the quality of life of children.
References
Ebrahimi A., Rahim F. Crigler-Najjar syndrome: current perspectives and the application of clinical genetics. Endocr Metab Immune Disord Drug Targets. 2018;18(3):201–211. DOI: 10.2174/1871530318666171213153130.
Иванова А.А., Максимов В.Н. Молекулярно-генетические аспекты синдрома Жильбера, синдромов Криглера-Найяра I и II. ЭиКГ. 2022;(8):56–62. DOI: 10.31146/1682-8658-ecg-204-8-56-62.
Abdel-Aziz Ali S.M., Mansour Galal S., Sror S.M., Hussein O., Abd-El-Haseeb Ahmed A.O., Hamed E.A. Efficacy of oral agar in management of indirect hyperbilirubinemia in full-term neonates. J Matern Fetal Neonatal Med. 2022; 35(5):975–980. DOI: 10.1080/14767058.2020.1740674.
Подымова С.Д. Пигментные гепатозы. Клинические особенности, пункционная биопсия, электронная микроскопия, диагноз, прогноз. Медицинский алфавит. 2018;2(20):15–22.
Готье М.С., Дегтярева А.В., Дегтярев Д.Н., Ушакова Л.В., Филиппова Е.А., Албегова М.Б. и др. Подходы к терапии синдрома Криглера–Найяра 1-го типа у детей. Вестник РГМУ. 2024;(6):5–12. DOI: 10.24075/vrgmu.2024.070.
Колотилина А.И. Сравнительная характеристика клинических и фенотипических признаков конъюгационной желтухи новорожденных и синдрома доброкачественной непрямой гипербилирубинемии у детей старшего возраста. Автореф. дис. … канд. мед. наук. М.; 2015.
He T., Geng X., Zhu L., Lin X., Wang L. Type II Crigler-Najjar syndrome: a case report and literature review. Front Med (Lausanne). 2024;11:1354514. DOI: 10.3389/fmed.2024.1354514.
Джулай Т.Е., Гаибова М.А., Демина А.Ю. Доброкачественные гипербилирубинемии разных видов у пациентов в сочетании с поражением органов пищеварения. Тверской медицинский журнал. 2022;4:154–157.
Ильченко Л.Ю., Федоров И.Г., Тотолян Г.Г., Цветкова А.Г., Гавриленко Е.Г., Миронов К.О., Никитин И.Г. Наследственная неконъюгированная гипербилирубинемия (сочетание синдрома Криглера-Найяра II типа и синдрома Жильбера). Гепатология и гастроэнтерология. 2021;(1):79–84.
Bortolussi G., Muro A.F. Advances in understanding disease mechanisms and potential treatments for Crigler-Najjar syndrome. Expert Opinion on Orphan Drugs. 2018;6:425–439.
Tcaciuc E., Podurean M., Tcaciuc A. Management of Crigler-Najjar syndrome. Med Pharm Rep. 2021;94 (Suppl 1):S64–S67. DOI: 10.15386/mpr-2234.
Giulia Bortolussi, Andrés Fernando Muro. Advances in understanding disease mechanisms and potential treatments for Crigler-Najjar syndrome. Expert Opinion on Orphan Drugs. 2018;6(7):425–439. DOI: 10.1080/21678707.2018.1495558.
Collaud F., Bortolussi G., Guianvarc’h L., Aronson S.J., Bordet T., Veron P., Charles S., Vidal P., Sola M.S., Rundwasser S., Dufour D.G., Lacoste F., Luc C., Wittenberghe L.V., Martin S., Le Bec C., Bosma P.J., Muro A.F., Ronzitti G., Hebben M., Mingozzi F. Preclinical development of an AAV8-hUGT1A1 vector for the treatment of Crigler-Najjar syndrome. Mol Ther Methods Clin Dev. 2018;12:157–174. DOI: 10.1016/j.omtm.2018.12.011.
D’Antiga L., Beuers U., Ronzitti G., Brunetti-Pierri N., Baumann U., Di Giorgio A., Aronson S., Hubert A., Romano R., Junge N., Bosma P., Bortolussi G., Muro A.F., Soumoudronga R.F., Veron P., Collaud F., Knuchel-Legendre N., Labrune P., Mingozzi F. Gene therapy in Patients with the Crigler-Najjar syndrome. N Engl J Med. 2023;389(7):620–631. DOI: 10.1056/NEJMoa2214084.
Каганов Б.С., Багаева М.Э., Баканов М.И., Басистова А.А., Глаголев Н.А., Готье С.В., Дворяковская Г.М. и др.; Б.С. Каганов, ред. Детская гепатология. М.: Династия; 2009.
