title: Chronic renal failure and proteinuria in adulthood: Fabry disease predominantly affecting the kidneys.
abstract: The prognosis of Fabry disease has changed since enzyme-replacement treatment was introduced. Therefore, early diagnosis is instrumental. We describe a family presenting with chronic renal failure and proteinuria in which classic skin and neurological features were absent and the diagnosis of Fabry disease was difficult and not established until a second family member developed renal abnormalities. A 35-year-old man was admitted because he was overweight and had hypertension, with a serum creatinine level of 1.3 mg/dL (115 micromol/L) and protein excretion of 870 mg/d. Because 1 brother, who died years ago at the age of 32 years of acute myeloid leukemia, also had chronic renal failure and proteinuria, the diagnosis of Fabry disease was entertained. In the index patient, acroparesthesia, hypohidrosis, pain, angiokeratomas of the skin, and cornea verticillata suggesting Fabry disease were absent. Conversely, renal biopsy showed typical globotriaosylceramide deposits, and leukocyte alpha-galactosidase (alpha-GLA) A activity was decreased. Analysis of the alpha-GLA gene showed the mutation E66K. The mutation also was found in another asymptomatic 30-year-old brother who also had chronic renal failure and proteinuria, but normal extrarenal findings. In the brother who died, Fabry disease, missed at autopsy because of cancer-related findings, could be confirmed after repeated review of histological slides. Mutation carriers also included the mother, a sister (both without abnormalities), and a nephew (with episodic pains in his feet). We conclude that familial chronic renal failure combined with proteinuria is suggestive of Fabry disease, and such specific mutations as E66K predominantly may affect the kidneys.
authors.affiliation: Department of Neprology, University Hospital of Freiburg; Institute of Pathology, Albert Ludwigs University, Freiburg, Germany. cybulla@med1.ukl.uni-freiburg.de
authors.forename: Markus
authors.initials: M
authors.lastname: Cybulla
authors.forename: Ellen
authors.initials: E
authors.lastname: Schaefer
authors.forename: Susanne
authors.initials: S
authors.lastname: Wendt
authors.forename: Hao
authors.initials: H
authors.lastname: Ling
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Kröber
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hövelborn
authors.forename: Stefan
authors.initials: S
authors.lastname: Schandelmaier
authors.forename: Rolf
authors.initials: R
authors.lastname: Rohrbach
authors.forename: Hartmut P H
authors.initials: HP
authors.lastname: Neumann
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002648:Child; D003404:Creatinine / Q000097:blood; D003937:Diagnosis, Differential; D000795:Fabry Disease / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications; D007668:Kidney / Q000737:chemistry / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009765:Obesity / Q000150:complications; D010375:Pedigree; D017354:Point Mutation; D011507:Proteinuria / Q000209:etiology*; D014281:Trihexosylceramides / Q000032:analysis
chemical_list: D014281:Trihexosylceramides; C018549:globotriaosylceramide; D003404:Creatinine