5782 AN EXCEPTIONAL CASE OF A PATIENT WITH TWO RARE GENETIC VARIANTS OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE AND ALPORT SYNDROME

• Published in: Nephrology, dialysis, transplantation Vol. 38; no. Supplement_1
• Main Authors: Venda, João, Henriques, Andreia Dos Santos, Leal, Rita, Alves, Rui
• Format: Journal Article
• Language: English
• Published: 14.06.2023
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfad063c_5782

Abstract Background Alport syndrome and autosomal dominant polycystic kidney disease (ADPKD) belong to the most prevalent monogenic causes of chronic kidney disease (CKD) and both progress to end stage renal disease (ESRD). Alport syndrome, is caused by mutations in genes encoding collagen IV protein family. Inheritance might be X-linked, autosomal recessive, autosomal dominant or digenic and several pathogenic variants have been identified. ADPKD is mostly caused by mutations in PKD1and PKD2 genes but recently, the GANAB gene, that encodes the glucosidase IIa subunit, has been identified has a cause of a milder form of ADPKD. We present a case report of a patients with CKD-4, bilateral sensorineural hearing loss and multiple renal cysts where two unrelated and distinct genetic variants of both diseases were concomitantly found. Case report A 63-year-old caucasian male with medical history of arterial hypertension, hematuria and bilateral sensorineural hearing loss since his 40 years-old, with cochlear implant surgery 13 years ago was referred to the Nephrology unit due to progressive CKD, currently stage 4. His mother had ESRD of unknown etiology, in peritoneal dialysis since the age of 78 years and he has two healthy sons (aged 16 and 20 years old). Physical examination was irremarkable. Laboratorial workout showed serum creatinine of 2.7 mg/dL, ratio albumin/creatinine of 105mg/g with 11 erythrocytes in urinary sediment. Renal ultrasound showed normal sized kidneys with more than 10 cysts in each kidney, the biggest with 44mm. Genetic testing via next generation sequencing was performed revealing heterozygous mutations in COL4A3 (c.4421T>C p.(Leu1474Pro)), reported in ClinVar, and described in literature as an autosomal dominant variant present in Alport families. A mutation in the GANAB (c.2281A>G p.(Thr761Ala)) gene, classified as variants of unknown significance in was also detected, but this mutations is not reported in gnomAD or ClinVar. The patient was referred for genetic counseling. Conclusion We describe a rare case of possible overlap of ADPKD and Alport syndrome. The COL4A3 mutation is described has having a risk ≥ 20% of developing ESRD, but the association of a mild variant of ADPKD might increase exponentially this risk.