Молодежный инновационный вестник

2415-7805

Федеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный медицинский университет имени Н.Н. Бурденко" Министерства здравоохранения Российской Федерации

10428

Conference Proceedings

Alagille syndrome: a clinical case in a child

Burlutskaya

Alla Vladimirovna

Doctor of Medical Sciences, Professor, Head of the Department of Pediatrics No. 2ped2@ksma.ruhttps://orcid.org/0000-0002-9653-6365Inozemtseva

Diana Andreyevna

Resident of the Department of Pediatrics No. 2 for 2 years of studygolubenko.1995@mail.ruhttps://orcid.org/0009-0001-6410-8884

Kuban State Medical University

25042025

14S1672674

25022025

23032025

2025

Relevance: Alagille syndrome is a genetic multisystem disease with an autosomal dominant type of inheritance and a wide range of clinical variability: from life-threatening conditions caused by critical heart defects, severe liver failure to subclinical mild forms with minor changes in the level of liver enzymes, which significantly complicates differential diagnosis. Alagille syndrome occurs with a frequency of 1 in 30,000 to 1 in 50,000 newborns. [1,2] Objective: to demonstrate the diagnosis of the rare genetic disease Alagille syndrome in a child. Materials and methods: The article describes a clinical case of Alajille syndrome in patient R., 1 month old, who was treated at the Children's Regional Clinical Hospital of the Krasnodar Territory. Results: Child R. was admitted to the younger department with complaints of jaundice of the skin, ecchymosis, and acolic stools. According to the results of the examination, cholestasis, cytolysis, hemorrhagic syndrome was revealed.

Alajil syndrome, autosomal dominant type of inheritance, progressive familial intrahepatic cholestasis

синдром Алажиля, аутосомно-доминантный тип наследования, прогрессирующий семейный внутрипеченочный холестаз

Relevance. Progressive familial intrahepatic cholestasis, the most common form of which is Alagille syndrome, is a group of rare hereditary diseases caused by a defect in the transport of bile acids from hepatocytes, leading to impaired bile secretion mechanisms, intrahepatic cholestasis, and the rapid development of liver cirrhosis.[3,4] Alagille syndrome occurs with a frequency of 1:30,000 to 1:50,000 newborns. [1] The goal. To analyze a clinical case of Alagille syndrome in a 1-month-old child. Materials and methods. A retrospective analysis of the patient's medical history was carried out for 1 month, who was being treated at the DCKB. Results. The patient, R. 1 months and 3 weeks old, was treated in the younger age department of the DCKB with complaints of jaundice of the skin, ecchymosis, and colorless stools. From the anamnesis of the disease: jaundice of the skin from the first day of life, acolic stools from birth. The condition is regarded as prolonged physiological jaundice. At 1 month of life, he was examined at his place of residence cytolysis, hyperbilirubinemia, stercobilin in the coprogram was negative. Viral infections, herpes are excluded, hepatitis markers are negative. Ultrasound of the gastrointestinal tract shows a narrowing of the intrahepatic bile ducts. To clarify the diagnosis, he was referred for hospitalization by the DCKB. Upon admission, the condition is of moderate severity. Weight 5200 g, height 57 cm. The body mass index Z-score is 0.17. The physique is normosthenic. The skin and mucous membranes are pale, icteric. Ecchymosis on the chest and arms. The subcutaneous fat layer is moderately developed and evenly distributed. There are no bone deformations. Breathing is puerile, there is no wheezing, the frequency is 46 per minute. Heart tones are clear, rhythmic, heart rate 140 beats/min, blood pressure 70/35 mmHg. The abdomen is symmetrical, soft, painless. The venous network on the abdomen is not pronounced. The liver is palpated 1 cm below the costal arch, the spleen is not palpable. The stool is mushy and regular. Male genitals, kidneys are not palpable, urination is free, urine is light. Laboratory tests: in the general blood test, platelets increased to 479 * 109 / l (norm 160-390), hemoglobin decreased to 97 g / l (norm 105-145), hematocrit 28.4% (norm 29-41%). Biochemical analysis shows an increase in total bilirubin to 208.8 mmol/l (norm 0-21), direct bilirubin to 176.4 mmol/l (norm 0-7), ALT to 267 U/l (norm 0-40), AST to 283 U/L (norm 0-60), HTT to 567 U/L (norm 0-204), alkaline phosphatase up to 1066 U/l (norm 70-518), creatinine up to 75 mmol/l (norm 18-35), cholesterol up to 6.7 mmol/l (norm 2.9-5.2), triglycerides up to 2.61 mmol/l (norm 0.34-1.13). Coagulogram: APTT 110.9 sec (norm 24-38), antithrombin III 137% (norm 83-128), factor VII 169% (norm 50-150), Willebrandt factor (antigen) 196% (norm 42-176%), reduction of hepatocomplex to 4% (norm 83-193%), protein S 10.3% (norm 63.5-149%), protein C 20% (norm 69-134%), factor IX 3.4% (norm 65-150%), prothrombin index 12% (norm 80-130), INR 8.65 (norm 0.8-1.1). ELISA is negative for viral hepatitis. Coprogram: grayish-white color, large amount of fatty acids, moderate amount of soap, negative reaction to stercobilin. Massive parallel panel sequencing (N.P. Bochkov Medical Genetic Research Center) revealed a heterozygous variant in exon 24 of the JAC1 gene (chr20:10621870CT) causing a missense substitution (NM_000214.3: p.2939GA, p.Cys980Tyr). According to the ACMG criteria, the variant is probably pathogenic (PP3, PM2, PM5). Pathogenic variants of the JAG1 gene are associated with Alagille syndrome, type 1 (OMIM #118450), autosomal dominant inheritance. Instrumental examination showed moderate hepatomegaly with diffuse changes in the liver parenchyma on the background of cholestasis, a slight decrease in renal kidney volume with diffuse changes in the parenchyma, a functioning oval window and an increased pressure gradient in the branches of the pulmonary artery (moderate stenosis) up to 30 mmHg. Esophagogastroduodenoscopy revealed eosinophilic gastritis and catarrhal bulbitis.In the department, the patient was treated with ademetionine, ursodeoxycholic acid, menadione, freshly frozen plasma (FFP), coaplex, aluminum phosphate. During therapy, the patient shows improvement due to relief of hemostasis disorders (acceleration of APTT, increased prothrombin index, antithrombin III, hepatocomplex, protein S and C, factor IX, decreased INR, Willerbrand factor), regression of hemorrhagic rash on the anterior chest wall and upper extremities. Conclusion: Doctors face considerable difficulties when trying to establish a correct diagnosis in the early stages of the disease, as the variety of symptoms can be misleading and complicate the diagnostic process. Nevertheless, modern advances in the field of molecular genetics open up new perspectives for the detection of Alagille syndrome at earlier stages of its development. Molecular genetic analysis is becoming a key tool that allows not only accurate diagnosis of the disease, but also the initiation of appropriate treatment at an early stage. This, in turn, significantly increases the chances of a favorable outcome and improves the prognosis for patients suffering from Alagille syndrome.

1. Российский вестник перинатологии и педиатрии 2020; 65:(2): 108–116. DOI: 10.21508/1027–4065–2020–65–2–108–116

2. Дегтярева А.В., Докшукина А.А., Готье М.С., Филиппова Е.А., Туманова Е.Л., Захарова Е.Ю., Албегова М.Б., Жданова С.И., Пучкова А.А., Исаева М.Х., Шубина Е., Гусарова Е.А. Ранние клинико-лабораторные и инструментальные характеристики синдрома Алажилля // Неонатология: новости, мнения, обучение. 2024. Т. 12, № 1. С. 27–36. DOI: https://doi. org/10.33029/2308-2402-2024-12-1-27-36

3. Федеральные клинические рекомендации по диагностике и лечению синдрома Аладжилля Авторский коллектив: Назаренко Л.П., профессор ФГБНУ «НИИ медицинской генетики», Томск; Клинические рекомендации рассмотрены на VII съезде Российского общества медицинских генетиков в Санкт Петербурге (19-23 мая 2015 г.) и утверждены председателем РОМГ, академиком РАН Е.К. Гинтером.

4. Hassan S, Hertel P. Overview of Progressive Familial Intrahepatic Cholestasis. Clin Liver Dis. 2022;26(3):371–390. https://doi.org/10.1016/j. cld.2022.03.003.