Abstract: TH-PO368
Characterization of Genetically Defined ARPKD-PKHD1 Patients Enriched for Childhood/Adult Onset
Session Information
- Genetic Diseases of the Kidneys: Cystic - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1101 Genetic Diseases of the Kidneys: Cystic
Authors
- Hanna, Christian, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Jawaid, Tabinda, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Senum, Sarah R., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Chedid, Maroun, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Madsen, Charles D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Chebib, Fouad T., Mayo Clinic in Florida, Jacksonville, Florida, United States
- Torres, Vicente E., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- El-Youssef, Mounif, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
ARPKD is generally considered a pediatric disorder with prominent phenotype variability related to kidney and liver involvement ranging from fetal demise to surviving into adulthood. Studies have shown phenotypic overlap between ARPKD and other ciliopathies. We aimed to characterize the clinical course in genetically defined ARPKD-PKHD1 patients (pts).
Methods
Through research or clinical genetic testing, pts were identified with biallelic PKHD1 variants. Identified families were characterized by segregation, imaging, and clinical phenotypes from chart review.
Results
Out of 47 pts with biallelic PKHD1, 37 (31 families) with complete clinical data were included (Table 1). Median age (Q1, Q3) at diagnosis and last follow-up were 1 (0, 20) and 30 yrs (20, 44), respectively, with a mean ± SD follow-up period of 19 ±12.5 yrs. Seventeen pts (46%) had in utero/infantile-onset (<1 yr), 10 (27%) with childhood-onset (1-17 yrs), and interestingly 10 (27%) with an adult-onset presentation with a median age of 42 (40, 44). At last follow up, kidney replacement therapy was present in 38%, portal hypertension in 65%, and liver transplant in 8%. Three pts (8%) died (1 neonate and 2 with adult-onset ARPKD). Kidney cysts, liver cysts, and nephrolithiasis (NL)/nephrocalcinosis (NC) were found in 89%, 24%, and 49%, respectively. Nephromegaly, hypertension, and kidney failure were more prevalent in utero/infantile-onset, and NL/NC in adult-onset (p≤0.05). A truncating (T) plus nontruncating (NT) variant were identified in 46% (17/37) and two NT variants in 54% (20/37); none had two T variants. No correlation was found between the genotypic group and diagnosis age (p=0.17).
Conclusion
In ARPKD-PKHD1 patients we found high variability in kidney and or liver phenotypes, including adult-onset ARPKD in the 5th decade and high prevalence of NL/NC. ARPKD should be considered a differential diagnosis in adults with fibrocystic hepatorenal disease with or without nephromegaly and NL/NC.
Table 1
Funding
- NIDDK Support