Abstract: SA-PO0179
Familial Hypocalciuric Hypercalcemia Is Not as Simple as Previously Thought: Assessment of Systemic Manifestations
Session Information
- Tubular, Metabolic, and Systemic Noncystic Genetic Kidney Diseases
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Borghol, Abdul Hamid, Cleveland Clinic, Cleveland, Ohio, United States
- Wang, Xiangling, Cleveland Clinic, Cleveland, Ohio, United States
Background
Familial hypocalciuric hypercalcemia (FHH) is a rare genetic disorder characterized by hypercalcemia and hypocalciuria. Although often considered a benign condition, its systemic manifestations have been rarely analyzed. In this study, we assess the systemic manifestations in patients with genetically confirmed FHH.
Methods
We conducted a retrospective study of 12 patients with genetically confirmed FHH evaluated at the Cleveland Clinic Renal Genetics Clinic from 2019, through 2025. Systemic manifestations and their associations with laboratory features including genotype were analyzed.
Results
Twelve patients with genetically confirmed FHH were included, with a median age of 34.3 years [IQR, 26.0-44.5], of whom 58% were female. The majority patients (11/12, 91.7%) carried a heterozygous pathogenic or likely pathogenic variant in CASR gene, while one had a pathogenic variant in GNA11 gene. Hyperlipidemia was present in 41.7% of patients, kidney stones in 25%, and fractures or dislocations in 33.3%. Psychiatric manifestations were identified in 6 patients (54.5%), most commonly major depressive disorder. There was no significant difference in serum calcium levels between patients with and without psychiatric manifestations (10.6 vs 10.8 mg/dL; P=0.84). Mixed-effects modeling showed no association between calcium and PHQ-9 scores (β=-2.76±3.33; P=0.41), and within-patient analyses showed no correlation between changes in calcium and depressive symptoms (Spearman ρ=-0.27; P=.16). Exploratory analyses suggested potential genotype-phenotype differences.
Conclusion
This is one of first studies assessing the systemic manifestations in FHH and have identified several important findings. Unexpectedly high prevalence of psychiatric manifestations, hyperlipidemia, and fractures/dislocation were observed in our FHH cohort. Larger studies are needed to confirm these findings, which may lead to changes in the monitoring and management of FHH.