title: A heterozygous female with Fabry disease due to a novel α-galactosidase A mutation exhibits a unique synaptopodin distribution in vacuolated podocytes.
abstract: We report the case of a 42-yearold woman diagnosed with heterozygous Fabry disease (FD) due to a novel α-galactosidase A Pro210Ser mutation and exhibiting a unique distribution of synaptopodin within podocytes. The patient was referred to our hospital with moderate proteinuria, and a renal biopsy was performed. Light microscopic examination of the specimen revealed diffuse global enlargement of podocytes, which also showed foamy changes. Electron microscopy revealed abundant myeloid bodies in podocytes and focal mitochondrial abnormalities within the tubules. The patient exhibited none of the characteristic symptoms of FD except hypohidrosis and had no obvious family history. Genetic analysis revealed a novel missense mutation (Pro210Ser) in the α-galactosidase A gene. She was ultimately diagnosed with FD based on immunohistochemical staining indicating large amounts of accumulated globotriaosylceramide in her podocytes, detection of urinary globotriaosylceramide secretion using high-performance thin-layer chromatography/ immunostaining, and structural modeling of the mutated α-galactosidase A (Pro210Ser). Immunostaining of the swollen and foamy podocytes using podocyte-associated antibodies (against podocalyxin, Wilms tumor-1, vimentin, and synaptopodin) revealed a unique distribution of synaptopodin surrounding globotriaosylceramide. To our knowledge, this is the first report of immunohistologically detected synaptopodin upregulation in foamy podocytes in a patient with FD.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Yokoi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kasuno
authors.forename: Akiya
authors.initials: A
authors.lastname: Kogami
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsukimura
authors.forename: Tadayasu
authors.initials: T
authors.lastname: Togawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Saito
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ohno
authors.forename: Masanori
authors.initials: M
authors.lastname: Hara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kurosawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hirayama
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kurose
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mikami
authors.forename: Hideki
authors.initials: H
authors.lastname: Kimura
authors.forename: Hironobu
authors.initials: H
authors.lastname: Naiki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakuraba
authors.forename: Masayuki
authors.initials: M
authors.lastname: Iwano
mesh_terms: D000328:Adult; D001706:Biopsy; D004252:DNA Mutational Analysis; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000032:analysis*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D020125:Mutation, Missense; D010641:Phenotype; D050199:Podocytes / Q000737:chemistry* / Q000648:ultrastructure; D014281:Trihexosylceramides / Q000032:analysis; D014617:Vacuoles / Q000737:chemistry* / Q000648:ultrastructure; D000519:alpha-Galactosidase / Q000235:genetics* / Q000627:therapeutic use
chemical_list: D008840:Microfilament Proteins; C503967:SYNPO protein, human; D014281:Trihexosylceramides; C018549:globotriaosylceramide; C576330:GLA protein, human; D000519:alpha-Galactosidase