Alagille syndrome associated with total anomalous pulmonary venous connection and severe xanthomas: A case report

Abstract

BACKGROUND Alagille syndrome (ALGS) is an autosomal dominant genetic disorder caused by mutations in the JAG1 or NOTCH2 gene. It is characterized by decreased intrahepatic bile ducts associated with a variety of abnormalities in many other organ systems, such as the cardiovascular, skeletal, and urinary systems. CASE SUMMARY We report a rare case of ALGS. A 1-month-old male infant presented with sustained jaundice and had a rare congenital heart disease: Total anomalous pulmonary venous connection (TAPVC). Sustained jaundice, particularly with cardiac murmur, caught our attention. Laboratory tests revealed elevated levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, and total bile acids, indicating serious intrahepatic cholestasis. Imaging confirmed the presence of butterfly vertebra at the seventh thoracic vertebra. This suggested ALGS, which was confirmed by genetic testing with a c.3197dupC mutation in the JAG1 gene. Ursodiol was administered immediately after confirmation of the diagnosis, and cardiac surgery was performed when the patient was 1.5 month old. He recovered well after treatment and was discharged at the age of 3 mo. At the age of two years, the patient returned to our clinic because multiple cutaneous nodules with xanthomas appeared, and their size and number increased over time. CONCLUSION We report a unique case of ALGS associated with TAPVC and severe xanthomas. This study has enriched the clinical manifestations of ALGS and emphasized the association between JAG1 gene and TAPVC.

A rare case of hepatoblastoma in a syndromic child with a de novo germline JAG1 mutation

“…17,18 A similar occurrence of total anomalous pulmonary venous return was reported in a case of Alagille syndrome with a frameshift mutation affecting exon 25. 19 Taken together, these cases point to JAG1 as a candidate gene for total anomalous pulmonary venous return and/or scimitar syndrome, perhaps associated with variants located in the last exons. Bile duct paucity was not observed in the patient; however, this feature, even though considered the most frequent characteristic of Débora Romeo Bertola and Ana Cristina Victorino Krepischi contributed equally to this study.…”