Joubert's syndrome as a cause of cholestasis in children

Literature review and a case report of Joubert syndrome in a preschool child are presented. This syndrome is accompanied by chronic intrahepatic cholestasis, characteristic facial dysmorphia, congenital malformations of the urinary system, eyes pathology, confirmed by a molecular genetic test of TMEM67 gene mutations. Diagnostic aspects of this pathology have been reviewed. The clinical case description. Boy K was admitted to the pediatric hepatology department with respiratory and renal failure, decompensated acidosis. On admission, complaints included shortness of breath, severe itching, pale and dry skin, poor appetite and delayed physical development. On examination, dysembryogenic stigmas: large head circumference, elongated face, protruding forehead, high rounded eyebrows, deeply set eyes, hypertelorism, antimongoloid incision of the eyes, low auricles. The skin was pale, dry with the scratch marks on the arms and legs flexor surfaces. Ankles, wrists skin lichenification, bruising and hyperpigmentation was observed. Moderate palmar erythema, spider veins on the abdomen, watch-glass nails were present. The abdomen was enlarged due to hepatosplenomegaly. A clinical and paraclinical examination was conducted, the patient was consulted by related specialists. Based on the obtained data and molecular genetic examination, the diagnosis was made. Conclusion. Joubert's syndrome may have a clinical presentation similar to that in cholestatic liver disease with typical clinical and laboratory symptoms. The molecular genetic testing is an important workup component in children with liver pathology combined with damage to other organs and systems. Successful treatment is possible providing a multidisciplinary approach used. The study was conducted by the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the abovementioned institution. Informed consent of the child's parents was obtained for the research. The authors declare no conflict of interest. Keywords: Joubert syndrome, cholestasis, children.

IL-13 as Target to Reduce Cholestasis and Dysbiosis in Abcb4 Knockout Mice

The Th2 cytokine IL-13 is involved in biliary epithelial injury and liver fibrosis in patients as well as in animal models. The aim of this study was to investigate IL-13 as a therapeutic target during short term and chronic intrahepatic cholestasis in an Abcb4-knockout mouse model (Abcb4−/−). Lack of IL-13 protected Abcb4−/− mice transiently from cholestasis. This decrease in serum bile acids was accompanied by an enhanced excretion of bile acids and a normalization of fecal bile acid composition. In Abcb4−/−/IL-13−/− double knockout mice, bacterial translocation to the liver was significantly reduced and the intestinal microbiome resembled the commensal composition in wild type animals. In addition, 52-week-old Abcb4−/−IL-13−/− mice showed significantly reduced hepatic fibrosis. Abcb4−/− mice devoid of IL-13 transiently improved cholestasis and converted the composition of the gut microbiota towards healthy conditions. This highlights IL-13 as a potential therapeutic target in biliary diseases.

Alagille syndrome in children

Alagill syndrome is a rare genetic disease with an autosomal dominant type of inheritance, which is characterized by chronic intrahepatic cholestasis due to an abnormality of the biliary tree in combination with multiple malformations. It presents certain difficulties in diagnosing little children, when it is necessary to accurately determine the cause of cholestasis and the tactics of further treatment.Objective. To analyze clinical manifestations and laboratory parameters in children with Alagill syndrome.Characteristics of children and research methods. The authors carried out a retrospective continuous analysis of the clinical and diagnostic manifestations of Alagill syndrome in 21 children (10 boys and 11 girls) aged from 1 month to 14 years 5 months (average age 5 years ± 1 year). They studied their history of life and illness, assessed the course of pregnancy, first clinical manifestations of the disease, the results of clinical and diagnostic tests at the beginning of the disease and the analyses conducted at the place of residence and during the first hospitalization. All children underwent ultrasound examination of the abdomen and biochemical blood test.Results. When analyzing clinical and diagnostic criteria of children with Alagille syndrome we found the following diagnostically important criteria: the threat of termination of pregnancy in mothers, fetal hypotrophy, prolonged neonatal period of jaundice, which may further persist and be accompanied by hepato / hepatosplenomegaly (more common for children above 3 months old), hypo-/ acholic stool, which occasionally occur in 3-month-old children, coagulopathy, more characteristic of children under 3 months old, as well as changes in biochemical blood parameters: the cytolytic activity – 2–5 times above the limits, hyperbilirubinemia (with a predominance of direct bilirubin fraction) – 3–7 times above the limits, gamma glutamyl – 2–7 times above the limits.Conclusion. Alagill syndrome should be diagnosed as early as possible to determine further treatment tactics. A detailed history, analysis of clinical and diagnostic manifestations of the disease, especially changes in biochemical blood tests are important for the diagnostics of this disease.

Successful Outcome of Chronic Intrahepatic Cholestasis in an Adult Patient with Sickle Cell/β+Thalassemia

Sickle cell/β+thalassemia (Hb S/β+thal) is considered as a variant form of sickle cell disease. Acute episodes of vasoocclusive pain crisis are characteristic for sickle cell disorders and may be complicated by an acute or chronic life-threatening organ dysfunction. Chronic intrahepatic cholestasis is a rare and severe complication in sickle cell disease, characterized by marked hyperbilirubinemia and acute hepatic failure with an often fatal course. Despite the fact that patients with Hb S/β+thal usually have a mild type of disease, herein we describe an interesting case of chronic intrahepatic cholestasis with successful outcome in an adult patient with Hb S/β+thal.