Adult-Onset Genetic Focal Segmental Glomerulosclerosis: A Tale of Two Mutations

• Main Author: Sousa,Luís Leite de
• Publication Date: 2023
• Other Authors: Pimenta,Gonçalo, Veríssimo,Rita, Theias,Rita, Carvalho,Tiago
• Format: Report
• Language: eng
• Source: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Download full: http://scielo.pt/scielo.php?script=sci_arttext&pid=S0872-01692023000100040
• topic: Glomerulosclerosis, Focal Segmental/diagnosis; Glomerulosclerosis, Focal Segmental/genetics

ABSTRACT Focal segmental glomerulosclerosis (FSGS) is a kidney histologic lesion that may be caused by multiple aetiologies and pathophysiological mechanisms, with podocyte injury and depletion as the common denominator. FSGS may be subdivided into different subclasses: primary, secondary, genetic and unknown forms. Notwithstanding the overlapping clinical and histological characteristics across the different forms of FSGS, their management and response to treatment are strikingly different. Genetic FSGS may be suggested by the appearance of nephrotic syndrome during childhood, but it may also present in adulthood, where the diagnosis is rather challenging due to widely variable clinical and histological phenotypes. Herein we present the case of a 34-year-old female with a family history of chronic kidney disease of undetermined aetiology, referred for a Nephrology consultation due to haematoproteinuria and de novo arterial hypertension. Complementary evaluation revealed a urinary protein/creatinine ratio of 4.3 g/g and albumin/creatinine ratio of 3.9 g/g with hypoalbuminaemia. Kidney biopsy revealed lesions of FSGS, associated with extensive foot process effacement. The constellation of findings and family history of kidney disease raised the suspicion of a genetic cause, therefore genetic testing was performed. Two variants in the NPHS2 gene [c.686G>A, p.(Arg229Gln) and c.855_856del, p(Arg286Thrfs*17)] were found in compound heterozygosity, compatible with the diagnosis of genetic FSGS. This case highlights the importance of a detailed evaluation of patients with FSGS lesions in order to identify the FSGS form, given its therapeutic and prognostic impact, including after kidney transplantation.