Clinical features and genetic analysis of nine Chinese children with Dent disease and identification of three novel CLCN5 and OCRL variants.

OBJECTIVE

This study aims to elucidate the genetic and phenotypic characteristics of pediatric patients with potential Dent disease (DD).

METHODS

High-throughput sequencing was conducted on 11 pediatric patients with potential cases of DD. We also analyzed clinical phenotype and treatment regimens.

RESULT: Variants in CLCN5 and OCRL were identified in nine patients, including three novel variants. The predominant clinical manifestations among these patients with a definitive diagnosis of DD included low molecular weight proteinuria (LMWP) (100%), hypercalciuria (66.7%), abnormal renal function (55.6%), nephrocalcinosis (44.4%), and hypophosphatemia (44.4%). Patients with CLCN5 or OCRL variants exhibited significantly elevated levels of both β2-microglobulin and α1-microglobulin, exceeding the normal threshold by more than tenfold. In contrast, the potential cases of DD without identified genetic mutations showed a moderate increase in β2-microglobulin (5-10 times the normal level), while α1-microglobulin levels remained below this range. Seven DD patients were treated with nonsteroidal angiotensin-converting enzyme inhibitors. By the end of this study, five DD patients were diagnosed with stage 2 chronic kidney disease (CKD2), while four were classified as having CKD1.

CONCLUSION

This study provides insight into the clinical and genetic profiles of DD patients. Notably, integrating genetic analysis with the detection of markedly elevated levels of LMWP, particularly α1-microglobulin,can substantially reduce the misdiagnosis of this disease.