Received January 31, 2008
Accepted on April 11, 2008

ORIGINAL ARTICLES

Renal Phenotype in Lowe Syndrome: A Selective Proximal Tubular Dysfunction

Detlef Bockenhauer ^*1, Arend Bokenkamp , William van't Hoff ^*, Elena Levtchenko , Joana E. Kist-van Holthe , Velibor Tasic ^||, and Michael Ludwig ^¶

*Department of Nephrology, Great Ormond Street Hospital, London, United Kingdom; Department of Pediatric Nephrology, Vrije Universiteit Medical Centre, Amsterdam, Department of Pediatric Nephrology, St. Radboud University Hospital, Nijmegen, and Department of Pediatric Nephrology, Leiden University Medical Centre, Leiden, the Netherlands; ||Department of Pediatric Nephrology, University Children’s Hospital, Skopje, Macedonia; and ¶Department of Clinical Biochemistry, University of Bonn, Bonn, Germany

¹ To whom correspondence should be addressed. E-mail: bocked{at}gosh.nhs.uk.

	Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: 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.