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Abstract: SA-PO746

The Clinicopathologic and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease Presenting in Adulthood

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic


  • Elhassan, Elhussein Aamir Elzein, Beaumont Hospital, Dublin, Ireland
  • Sarihan, Sahin, Royal College of Surgeons in Ireland, Dublin, Dublin, Ireland
  • McAnallen, Susan Marie, Beaumont Hospital, Dublin, Ireland
  • Dunne, Orla Marie, Letterkenny University Hospital, Letterkenny, Donegal, Ireland
  • Benson, Katherine A., Royal College of Surgeons in Ireland, Dublin, Dublin, Ireland
  • Cavalleri, Gianpiero, Royal College of Surgeons in Ireland, Dublin, Dublin, Ireland
  • Conlon, Peter J., Beaumont Hospital, Dublin, Ireland

Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy that causes massively enlarged kidneys and pulmonary hypoplasia in perinatal children, frequently leading to fetal demise. In the survivors, ductal plate malformation often causes congenital hepatic fibrosis and Caroli disease. However, the spectrum of presentation and disease varies considerably.


We examined the clinicopathologic characteristics of PKHD1-defined ARPKD. Genetic testing was performed using whole exome sequencing.


Three unrelated families (4 adult individuals) were identified to harbor disease-causing PKHD1 variants sequenced by the Irish Kidney Gene Project. The average age of initial presentation was 16.5 ± 18.6 years. In family (1), we identified biallelic PKHD1 variants (NM_138694.4: c.2702A>C;p.N901T & c.107C>T;p.T36M) in a female patient with congenital hepatic fibrosis and non-enlarged cystic kidneys, during the evaluation of elevated creatinine. She had gradually progressed into ESKF at 53 years of age. In family (2), the renal-limited phenotype of PKD was identified in two siblings. No liver involvement was identified. The two siblings detected a homozygous missense variant in the PKHD1 gene, NM_138694.4: c.5221G>A;p.V1741M. Patients progressed to ESKF at ages 36 and 40 years, respectively. In family (3), the index patient presented with predominant hepatic phenotype - recurrent cholangitis, portal hypertension, and Caroli disease at clinical disease-onset aged 48 years. A liver biopsy was performed and demonstrated marked liver fibrosis with numerous multifocal cystic dilatation of intrahepatic ducts. She was found to have multiple small bilateral kidney cortical cysts with impaired function. At the last assessment, aged 61 years, she developed slowly progressive kidney insufficiency, with a serum creatinine of 201 µmol/L and creatinine clearance of 23 ml/min about 15 years after her presentation. Exome-sequencing revealed pathogenic biallelic PKHD1 variants (NM_138694.4; c.8068T>C; p.W2690R and c.338delG; p.G113Dfs*4).


While ARPKD is remarked with early-onset and high disease mortality, these cases illustrate disease heterogeneity, and PKHD1-defined ARPKD is not merely a pediatric disease.