Clinical and genetic characteristics of Russian children with Dent's disease and Lowe syndrome: a single-center experience

Dent disease and Lowe syndrome are hereditary tubulopathies characterized by low-molecular-weight proteinuria, hypercalciuria, and nephrocalcinosis. Proteinuria may reach high levels, necessitating differential diagnosis with steroid-resistant nephrotic syndrome.

Materials and Methods: from 2010 to 2025, 41 children with Dent disease or Lowe syndrome were followed at the Nephrology Department of the National Medical Research Center for Children's Health. Dent disease type 1 was confirmed in 29 children (71%), type 2 in 3 children (7%), and type 3 in 3 children (7%). Lowe syndrome was diagnosed in 6 children (15%).

Results: all children exhibited low-molecular-weight proteinuria, ranging from 139 to 3,653 mg/m²/day, with a median of 1,590 (952; 2248) mg/m²/day. Ultrasound signs of nephrocalcinosis were observed in 61% of patients, and hypercalciuria was detected in 66%.

Molecular genetic testing identified causative variants in the CLCN5 and OCRL genes in all but three children. Nearly all detected pathogenic variants were unique; only one variant, CLCN5 c.2320C>T was found in two unrelated children.

At the time of analysis (mean age 9 years 8 months, SD 5 years 1 months), decreased renal function was present in 41% of patients. Renal replacement therapy was required in only one child (2%). No correlations were found between decreased estimated GFR and maximum proteinuria level, presence of nephrocalcinosis, or growth retardation. However, a significant correlation was observed between growth Z-score and the daily proteinuria level (ϱ=-0.451, p<0.01).

Conclusions: Dent disease and Lowe syndrome can be clinically based on laboratory and instrumental findings, with molecular genetic testing confirming the diagnosis.

Given the wide variety of variants identified in the CLCN5 and OCRL genes, establishing genotype-phenotypic correlations is challenging and requires further investigation in larger cohorts.

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