title: Renal phenotype in Lowe Syndrome: a selective proximal tubular dysfunction.
abstract: OBJECTIVE
  Lowe syndrome is defined by congenital cataracts, mental retardation, and proximal tubulopathy and is due to mutations in OCRL. Recently, mutations in OCRL were found to underlie some patients with Dent disease, characterized by low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis. This phenotypic heterogeneity is poorly understood.
  
  
  METHODS
  The renal phenotype of 16 patients with Lowe syndrome (10.9 +/- 7.0 yr) under care of the authors was characterized to define overlap of symptoms with Dent disease and infer clues about OCRL function. Medical charts of patients were reviewed for data regarding glomerular filtration rate and markers of proximal tubular function.
  
  
  RESULTS
  All patients had low molecular weight proteinuria and albuminuria. Lysosomal enzymuria was elevated in all 11 patients assessed. Fifteen patients had hypercalciuria, and 14 aminoaciduria. Seven patients required bicarbonate and three required phosphate replacement; all others maintained normal serum values without supplementation. None of the patients had detectable glycosuria, and none had clinically overt rickets. GFR was mildly to moderately impaired and highly variable, with a trend of deterioration with age.
  
  
  CONCLUSIONS
  Patients with Lowe syndrome do not have renal Fanconi syndrome but a selective proximal tubulopathy, variable in extent and dominated by low molecular weight proteinuria and hypercalciuria, the classical features of Dent disease. These findings suggest that OCRL and ClC-5, the chloride channel mutated in Dent disease, are involved in similar reabsorption pathways in the proximal tubule.
authors.affiliation: Department of Nephrology, Great Ormond Street Hospital, London, United Kingdom. bocked@gosh.nhs.uk
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
authors.forename: Arend
authors.initials: A
authors.lastname: Bokenkamp
authors.forename: William
authors.initials: W
authors.lastname: van't Hoff
authors.forename: Elena
authors.initials: E
authors.lastname: Levtchenko
authors.forename: Joana E
authors.initials: JE
authors.lastname: Kist-van Holthe
authors.forename: Velibor
authors.initials: V
authors.lastname: Tasic
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
mesh_terms: D000141:Acidosis, Renal Tubular / Q000235:genetics / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000235:genetics / Q000503:physiopathology; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005060:Europe; D005198:Fanconi Syndrome / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate; D006029:Glycosuria / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D053565:Hypercalciuria / Q000235:genetics / Q000503:physiopathology; D007015:Hypophosphatemia, Familial / Q000235:genetics / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000503:physiopathology*; D016464:Lysosomal Storage Diseases / Q000235:genetics / Q000503:physiopathology; D008297:Male; D009154:Mutation; D009397:Nephrocalcinosis / Q000235:genetics / Q000503:physiopathology; D009800:Oculocerebrorenal Syndrome / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics / Q000503:physiopathology; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics* / Q000503:physiopathology
chemical_list: D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human