Alagille syndrome in children: clinical cases

Background. Alagille syndrome is a hereditary multisystem pathology that is transmitted in an autosomal dominant manner. The disease is characterized by significant clinical heterogeneity, from life-threatening severe cardiac abnormalities and severe liver dysfunction to mild forms with minor abnormalities in liver enzyme levels. This variability complicates differential diagnosis. It is noteworthy that the degree of manifestation of the syndrome can vary greatly even among relatives with the same genetic mutations. The disease occurs with a frequency of 1:30,000-1:50,000 newborns. Results. The article presents three clinical cases of Alagille syndrome: patient R., 1 month old, patient C., 3 months old, and patient B., 5 months old. All children had symptoms of cholestasis from the first days of life, including jaundice of the skin and sclera, acolic stools, elevated total bilirubin with a predominance of the direct fraction, and a negative reaction to stercobilin in the stool. Two patients with cholestasis developed cholestatic hepatitis with a high degree of activity, manifested by increased transaminases and echographic signs of diffuse liver changes. In children aged 1 and 5 months, manifestations of hemorrhagic syndrome were revealed, which was clinically manifested by the presence of ecchymoses. All the examined patients developed secondary anemia due to liver damage. A patient of 3 months and 5 months of the presented clinical cases had a specific syndrome in the form of "butterfly-shaped" vertebrae. These patients also had a hemodynamically significant congenital heart defect. According to the results of mass parallel panel sequestration, pathogenic variants in the JAG1 gene were found in all patients. Conclusion. Alagille syndrome is characterized as a multifactorial pathological condition characterized by significant clinical heterogeneity, which significantly complicates the diagnostic process in the first three months after the patient's birth. The identification of specific clinical and instrumental markers associated with this syndrome is a key element in the early diagnosis system. This allows not only to prevent the progression of severe disabling complications, but also to form sound strategies for clinical management and therapeutic intervention in patients with this syndrome.