title: Female Patient with Alport Syndrome and Concomitant Membranous Nephropathy: Susceptibility or Association of Two Diseases?
abstract: Alport syndrome (AS) is a disorder of collagen IV, a component of glomerular basement membrane (GBM). The association of AS and immunocomplex nephropathies is uncommon. This is a case of a 37-year-old woman with family history of X-linked AS, including 4 affected sons. This patient developed full-blown nephrotic syndrome along a 3-month period, a presentation not consistent with AS progression. This scenario suggested an alternative diagnosis. A kidney biopsy was therefore performed, showing membranous nephropathy (MN) in addition to GBM structural alterations compatible with AS. Whole exome sequencing also confirmed the diagnosis of X-linked AS, revealing a heterozygous pathogenic mutation in COL4A5. While a negative serum anti-phospholipase A2 receptor did not rule out a primary form of MN, it was also uncertain whether positive serologic tests for syphilis could represent a secondary factor. It is currently unknown whether this unusual association represents AS susceptibility to immunocomplex-mediated diseases or simply an association of 2 disorders.
authors.affiliation: Division of Nephrology, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Mariana P
authors.initials: MP
authors.lastname: Veloso
authors.forename: Precil D M M
authors.initials: PDMM
authors.lastname: Neves
authors.forename: Lectícia B
authors.initials: LB
authors.lastname: Jorge
authors.forename: Cristiane B
authors.initials: CB
authors.lastname: Dias
authors.forename: Luis
authors.initials: L
authors.lastname: Yu
authors.forename: Rafaela B B
authors.initials: RBB
authors.lastname: Pinheiro
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Testagrossa
authors.forename: Denise M
authors.initials: DM
authors.lastname: Malheiros
authors.forename: Bruno E P
authors.initials: BEP
authors.lastname: Balbo
authors.forename: Antônio M
authors.initials: AM
authors.lastname: Lerário
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Onuchic
authors.forename: Viktoria
authors.initials: V
authors.lastname: Woronik
mesh_terms: D000328:Adult; D024141:Collagen Type IV / Q000235:genetics; D018450:Disease Progression; D004198:Disease Susceptibility; D059472:Exome; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000150:complications* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology; D009154:Mutation; D009394:Nephritis, Hereditary / Q000150:complications* / Q000235:genetics / Q000473:pathology; D009404:Nephrotic Syndrome / Q000209:etiology / Q000235:genetics; D010375:Pedigree
chemical_list: C478159:COL4A5 protein, human; D024141:Collagen Type IV
keywords: Alport syndrome; COL4A5; Hereditary nephritis; Membranous nephropathy; Nephrotic syndrome; Whole exome sequencing