Abstract: FR-PO610
Autosomal Recessive Polycystic Kidney Disease (ARPKD) Presenting in Adulthood
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
- Kodali, Ravi, Yale School of Medicine, Madison, Connecticut, United States
- Dahl, Neera K., Yale School of Medicine, Madison, Connecticut, United States
Group or Team Name
- Yale University
Introduction
ARPKD is characterized by multiple renal cysts arising from the collecting ducts, variable degree of progressive renal failure and congenital hepatic fibrosis. It is caused by mutations in PKHD1 gene located on chromosome 6p21. It is mostly diagnosed in infancy or childhood with only few cases being diagnosed as adults. Here we present a case of ARPKD that was diagnosed in adulthood.
Case Description
A 37-year-old female with past medical history significant for congenital hepatic fibrosis is referred to polycystic kidney disease clinic for evaluation of cystic kidney disease. Family history is significant for cystic kidney disease in two of her cousins (both on the paternal side). Neither of her parents had a history of kidney cysts. Her renal function was normal. Abdominal MRI revealed a cirrhotic liver with extensive fibrocystic changes and splenomegaly. It also showed several sub-centimeter cysts in both kidneys (Figure 1). Whole exome sequencing showed compound heterozygous variants of PKHD1; one, c.3761_3762delCCinsG is known to be pathogenic.The other, c.9107T>G, is a variant of unknown significance (VUS). This is a rare variant (2/100,000) which has previously been detected in at least 2 ARPKD patients, with clinical presentations of hepatic fibrosis.
Discussion
There are more than 750 different mutations described in PKHD1 gene. Most common amongst these is a missense mutation in exon 3. Our patient has a compound heterozygous mutation. The first allele had a mutation in exon 32. This involves deletion of two nucleotides and addition of a third nucleotide leading to a frameshift mutation which leads to a premature stop codon. This is a known pathogenic mutation. Less is known about the second variant, c.9107T>G although it has been described in ARPKD patients presenting with hepatic fibrosis and normal kidney function. Adult onset ARPKD is rare, and notable. The combination of hepatic fibrosis, splenomegaly and kidney cysts are consistent with ARPKD, although in this patient the liver findings dominate.