[UGT1A1 gene mutation spectrum with indirect hyperbilirubinemia in children].

Objective: To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children. Methods: Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis. Results: Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211G > A accounted for 37.5% (6/16), c.1456T > G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin (t = 5.539, P < 0.05), and indirect bilirubin (t = 5.312, P < 0.05). However, there was no significant difference in direct bilirubin levels (t = 1.223, P > 0.05) and age of onset (t = 0.3611, P > 0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456T > G homozygous mutations had the highest serum bilirubin levels. Conclusion: The common pathogenic variants of the UGT1A1 gene sequence are c.1456T > G, c.211G > A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.

Unusual presentation of Gilbert disease with high levels of unconjugated bilirubin. Report of two cases

Gilbert’s syndrome is a benign condition characterized by asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation. Under certain physiologic or pathologic events, bilirubin level rises but according to literature it does not reach out more than 3 mg/dl. We report 2 cases of Gilbert’s syndrome, genetically tested, which presented with bilirubin levels above 6 mg/dl without any trigger or coexisting condition. In conclusion, bilirubin levels higher than 6 mg/dl in Gilbert syndrome are rare, hemolytic and other metabolism diseases must be ruled out, and enetic testing may be necessary in some cases (AU)

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Síndrome de Dubin-Johnson y embarazo: primer caso clínico en Venezuela / Dubin-Johnson syndrome: first Venezuela case clinic

Se describe el primer caso nacional de una embarazada con síndrome de Dubin-Johnson. El síndrome se caracteriza por una hiperbilirrubinemia crónica a predominio de la directa de origen familiar, no hemolítica, debido a un trastorno del transporte de la bilirrubina del hepatocito hasta el canalículo biliar y depósito en el hepatocito de un pigmento oscuro, similar a la melamina. La ictericia, usualmente ausente en el primer trimestre, aumenta en el segundo y sobre todo en el tercer trimestre del embarazo. En nuestro caso, la paciente es II gesta, II para, en ambos embarazos se observó el patrón clínico y bioquímico, con exacerbación durante el tercer trimestre y valores más acentuados en el segundo embarazo. Las dos gestaciones cursaron normalmente y en ambos se obtuvieron recién nacidos normales sin posteriores complicaciones

Identificación de defectos moleculares en las enfermedades hepáticas: ejemplos recientes / Identification of molecular defects in liver diseases: recent advances

Recent molecular studies have resulted in the identification of genetic alterations underlying several hereditary disorders of the liver. Cloning of disease genes are increasing our understanding of the basic defects in liver diseases. This review focuses on selected inherited liver diseases such as hyperbilirubinemic syndromes, hemochromatosis, Wilson disease and genetic cholestatic syndromes and illustrate the knowledge gained on these disorders from molecular studies. Potential implications of the identification of disease genes such as practical applications for diagnosis, information on prognosis and the possibility to design new therapies are discussed