Lada Beara Lasic
Project Summary and relevance
Dent disease is a rare genetic disorder that most commonly presents with low molecular weight proteinuria, hypercalciuria, nephrolithiasis and nephrocalcinosis and may cause renal failure. Most patients affected by this X-linked recessive disorder have mutations in one of two known genes, CLCN1 or OCRL1. Due to its rarity, most physicians typically have limited training and experience with Dent disease patients over the course of a normal practice. It is reasonable to suspect that a number of cases of Dent disease remain undiagnosed. Therefore, many aspects of Dent Disease are not yet well defined, and there has been little opportunity to critically evaluate possible treatments.
In this Rare Disease Center (RDC) proposal, funded by NIDDK and the Office of Rare Diseases (ORD), a Dent disease registry, modeled on the successful primary hyperoxaluria registry maintained at Mayo Clinic, will be established. Patients will be enrolled through solicitation of urology and nephrology clinical practices, as well as through available patient contacts through existing social networks. A mutation database will be a long term goal of the registry that would promote structure-function analysis of CLCN5 or OCRL1 mutations and easy identification of sequence polymorphisms that have no phenotypic effect. Eventually, when sufficient data is obtained, the effects of newly-discovered mutations can be predicted and modifier loci mapped.
Many features of the disease important for optimizing treatment remain poorly understood. Previous studies have lacked sufficient patient numbers and long term follow up. Important questions to be studied in this proposal include: 1) what factors other than genotype, such as age, gender, diet, and medications affect stone formation; 2) what risks factors account for the increased risk of chronic kidney disease in Dent disease; 3) which medications can modify progression into chronic kidney disease. The Dent disease registry will lead to the largest longitudinal clinical registry to allow determination of the risk factors for chronic kidney disease and stone recurrence in patients with Dent disease. We aim to develop patient support group to encourage registry enrollment and disseminate knowledge and information to patients and practitioners. We are hoping that the data collected in this registry will allow patterns and associations to be discovered that will expand our understanding of Dent disease.