Renal phenotype in Lowe Syndrome: a selective proximal tubular dysfunction

Area of Science:

• Nephrology
• Genetics
• Molecular Biology

Background:

• Lowe syndrome, caused by OCRL mutations, presents with cataracts, intellectual disability, and proximal tubulopathy.
• Some Dent disease cases also involve OCRL mutations, presenting with proteinuria, hypercalciuria, and nephrocalcinosis.
• The phenotypic variability in OCRL-related disorders is not well understood.

Purpose of the Study:

• To characterize the renal phenotype in Lowe syndrome patients.
• To identify overlapping symptoms with Dent disease.
• To gain insights into OCRL function in the kidney.

Main Methods:

• Retrospective review of medical charts for 16 Lowe syndrome patients.
• Assessment of glomerular filtration rate (GFR) and proximal tubular function markers.
• Analysis of proteinuria, albuminuria, lysosomal enzymuria, and aminoaciduria.

Main Results:

• All patients presented with low molecular weight proteinuria and albuminuria.
• Elevated lysosomal enzymuria was observed in 11 patients; 15 had hypercalciuria.
• GFR was mildly to moderately impaired and showed age-related deterioration; glycosuria and rickets were absent.

Conclusions:

• Lowe syndrome involves a selective proximal tubulopathy, not a full Fanconi syndrome.
• Key features include proteinuria and hypercalciuria, characteristic of Dent disease.
• OCRL and ClC-5 (mutated in Dent disease) likely participate in similar proximal tubule reabsorption processes.