Abstract: FR-PO617
Biallelic PKD1 Mutations in a Child with Aggressive Autosomal Dominant Polycystic Kidney Disease and Congenital Hepatic Fibrosis
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
- 1001 Genetic Diseases of the Kidney: Cystic
Authors
- Fulchiero, Rosanna, Inova Fairfax Children's Hospital, Falls Church, Virginia, United States
- Diamonstein, Callie, Inova Translational Medicine Institute, Falls Church, Virginia, United States
- Chao, Catherine S., Pediatric Specialists of Virginia, Oak Hill, Virginia, United States
- Mani, Haresh, Inova Fairfax Hospital, Falls Church, Virginia, United States
- Hauser, Natalie S., Inova Fairfax Hospital, Falls Church, Virginia, United States
- Seo-Mayer, Patricia, Pediatric Specialists of Virginia (Inova-CNMC) and Georgetown University School of Medicine, Fairfax, Virginia, United States
Introduction
Autosomal recessive polycystic kidney disease (ARPKD) is generally characterized by neonatal detection of enlarged kidneys and pulmonary hypoplasia. Autosomal dominant PKD (ADPKD) usually manifests in adulthood with hypertension and nephromegaly. Both have gastrointestinal manifestations - congenital hepatic fibrosis (CHF) is common in ARPKD, while ADPKD patients more typically have polycystic liver disease. CHF has been rarely reported in cases of ADPKD, but specific modifier genes have not been identified. We report the case of a child with aggressive ADPKD and CHF in the context of a biallelic mutation of PKD1.
Case Description
We report the case of a term male infant of African descent presenting with neonatal nephromegaly, pulmonary hypoplasia and hypertension. ARPKD was suspected initially, but genetic testing did not identify a pathogenic mutation in PKD2 or PKHD1. Instead, two variants on the PKD1 gene were identified (c.11249G>A and c.6395T>G), one of which was previously unreported. His course was complicated by anemia, hypertension, respiratory insufficiency and progressive CKD. At 20 months of age, he became acutely ill with fever, ascites, and worsening abdominal distension and was diagnosed with spontaneous bacterial peritonitis. Liver imaging showed hepatomegaly with normal liver function tests. Renal function deteriorated, requiring hemodialysis and ultimately, nephrectomies. Kidney biopsy showed diffuse cysts involving all segments of the nephron, complete obliteration of the cortex and glomerulocystic changes. Liver biopsy demonstrated CHF, with diffuse ductal plate malformation, tortuous peripheral ductal profiles and expanded portal tracts. Doppler ultrasound did not reveal portal hypertension.
Discussion
Our patient has a previously unreported variant of PKD1, and biallelic or “double dominant” ADPKD. This case is significant due to his neonatal presentation, early deterioration of renal function, and CHF, all of which are unusual in ADPKD. This suggests that biallelic ADPKD has unique clinical characteristics. This case emphasizes the importance of considering a wider differential diagnosis when evaluating children with nephromegaly and cystic kidney disease; and the importance of monitoring for CHF and related sequelae, even in the context of ADPKD.