Abstract: FR-PO618
Mutation in NOTCH2 Gene Causing Liver and Renal Failure in Newborn
Session Information
- Trainee Case Reports - IV
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1002 Genetic Diseases of the Kidney: Non-Cystic
Authors
- Tran, Thu, Texas Tech University Health Sciences Center, Amarillo, TX, Amarillo, Texas, United States
- Chhin, Rasmey, Texas Tech University Health Sciences Center, Amarillo, TX, Amarillo, Texas, United States
- Vasylyeva, Tetyana L., Texas Tech University Health Sciences Center, Amarillo, TX, Amarillo, Texas, United States
Introduction
Alagille syndrome is an autosomal dominant disorder known to cause a multi-organ dysfunction and often presents as neonatal liver disease. The majority of cases are related to the mutation of the JAG1 gene and only a small percentage, <1%, is due to mutation of the NOTCH2 gene. We present a patient who was diagnosed with neonatal giant cell hepatitis and renal tubular dysgenesis later found to have NOTCH2 gene mutation.
Case Description
The patient delivered at 39 weeks gestation via cesarean section due to being large for gestational age and appeared “swollen” on ultrasound. At 6 weeks of life, he was found to have elevated transaminases, hyperbilirubinemia, clay colored stools, rust colored urine and ascites. A liver biopsy was done and read as neonatal giant cell hepatitis with marked hemosiderosis, bile duct paucity, and acute microabscess. At 5 months of life, he was admitted for acute kidney failure when found to have oliguria, hyperkalemia, rising creatinine levels and coagulation levels indicative of disseminated intravascular coagulation. He underwent orthotopic liver transplantation at that time. A biopsy was done on the explanted liver and found hepatocellular necrosis with syncytial giant cell transformation and diffuse fibrosis with marked hemosiderosis which was highly concerning for possible embryonal hepatoblastoma versus neonatal hemochromatosis. He required a prolonged period of continuous renal replacement therapy and dialysis which prompted a fine needle biopsy of the kidneys revealing renal tubular dysgenesis. Repeated biopsy at the age of 4 years showed glomeruli with podocyte hypertrophy and fetal glomerular appearance. Whole exome sequencing was later done and revealed he had an unclassified variant detected of phenotype H2032N which is found in the NOTCH2 gene and known to be linked to Alagille syndrome.
Discussion
Alagille syndrome is characterized by bile duct paucity but has the classical involvement of 5 main systems including: liver, dysmorphic facies, congenital heart disease, skeletal anomalies, and ophthalmic defects. Both the JAG1 gene and the NOTCH2 genes are involved with the Notch receptors. JAG1 gene is responsible for up to 95% of cases while the NOTCH2 gene is involved in <1% of cases. This case highlights the extensive multisystem involvement that can be seen in Alagille syndrome and the extremely rare presentation of the NOTCH2 gene mutation.