Coexistence of autosomal dominant polycystic kidney disease type 1 and hereditary renal hypouricemia type 2: A model of early-onset and fast cyst progression.

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous inherited disease characterized by renal and extrarenal manifestations with progressive fluid-filled cyst development leading to end-stage renal disease. The rate of disease progression in ADPKD exhibits high inter- and intrafamilial variability suggesting involvement of modifier genes and/or environmental factors. Renal hypouricemia (RHUC) is an inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and chronic kidney disease (CKD). However, the two disorders have distinct and well-delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and RHUC (type 1) in a single individual have been reported. We report a family with two members: an ADPKD 24-year-old female which presented bilateral renal cysts in utero and hypouricemia since age 5, and her mother with isolated hypouricemia. Next-generation sequencing identified two mutations in two genes PKD1 and SLC2A9 in this patient and one isolated SLC2A9 mutation in her mother, showing RHUC type 2, associated to CKD. The coexistence of these two disorders provides evidence of SLC2A9 variant could act as a modifier change, with synergistic actions, that could promote cystogenesis and rapid ADPKD progression. This is the first case of coexistence of PKD1 and SLC2A9 mutations treated with tolvaptan.

• Authors: Ramón Peces, Rocio Mena, Carlos Peces, Emilio Cuesta, Rafael Selgas, Pilar Barruz, Pablo Lapunzina, Julián Nevado
• Journal: Clinical genetics (Clin Genet) Vol. 97 Issue 6 Pg. 857-868 (06 2020) ISSN: 1399-0004 [Electronic] Denmark
• PMID: 32166738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Glucose Transport Proteins, Facilitative
• SLC2A9 protein, human
• TRPP Cation Channels
• polycystic kidney disease 1 protein

Topics

• Acute Kidney Injury (complications, diagnosis, genetics, pathology)
• Adult
• Child, Preschool
• Female
• Glucose Transport Proteins, Facilitative (genetics)
• Humans
• Mutation (genetics)
• Polycystic Kidney Diseases (complications, diagnosis, genetics, pathology)
• Polycystic Kidney, Autosomal Dominant (complications, diagnosis, genetics, pathology)
• Renal Insufficiency, Chronic (complications, diagnosis, genetics, pathology)
• Renal Tubular Transport, Inborn Errors (complications, diagnosis, genetics, pathology)
• TRPP Cation Channels (genetics)
• Young Adult