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Multicenter Study
. 2008 Sep;3(5):1430-6.
doi: 10.2215/CJN.00520108. Epub 2008 May 14.

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, Michael Ludwig
Affiliations
Multicenter Study

Renal phenotype in Lowe Syndrome: a selective proximal tubular dysfunction

Detlef Bockenhauer et al. Clin J Am Soc Nephrol. 2008 Sep.

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.

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Figures

Figure 1.
Figure 1.
Plotted are estimated GFR values of individual patients over time. Estimations were based on 14 formal GFR measurements using 51Cr-EDTA for seven patients, using a modified Schwartz-Haycock formula (see text). Note the high inter- and intraindividual variability with a trend for deterioration with age.
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