ECEESPE2025 Poster Presentations Bone and Mineral Metabolism (112 abstracts)
Autosomal dominant hypocalcemia type 1 or type 2: baseline characteristics of pediatric participants in the CLARIFY disease monitoring study
Raja Padidela 1 , Matthew Benson 2 , Justine Bacchetta 3 , Tariq Ahmad 4 , Christina Jacobsen 5 , Agnès Linglart 6 , Peter Tebben 7 , Takuo Kubota 8 , Nina S. Ma 9 , Stefano Mora 10 , Halley Wasserman 11 , Jessica Chen 12 , DingFeng Li 12 , Mary Scott Roberts 12 , Scott Adler 12 & Outi Mäkitie 13
1Royal Manchester Children’s Hospital & Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom; 2Nemours Children’s Clinic, Jacksonville, United States; 3Hospices Civils de Lyon, INSERM1033, Lyon, France; 4University of California San Francisco - Benioff Children’s Hospital, Oakland, United States; 5Boston Children’s Hospital, Boston, United States; 6Paris Saclay University, AP-HP Hopital Bicetre, Le Kremlin-Bicêtre, France; 7Yale University School of Medicine, New Haven, United States; 8Osaka University Hospital, Suita, Japan; 9Children’s Hospital Colorado, Aurora, United States; 10Laboratory of Pediatric Endocrinology, Department of Pediatrics, IRCCS Ospedale San Raffaele, Milano, Italy; 11Cincinnati Children’s Hospital Medical Center, Cincinnati, United States; 12Calcilytix Therapeutics, San Francisco, United States; 13Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
JOINT1369
Autosomal dominant hypocalcemia type 1 (ADH1) and type 2 (ADH2) are rare disorders caused by activating variants of the CASR and GNA11 genes, respectively. The calcium-sensing receptor (CaSR) plays a critical role in calcium homeostasis by signaling parathyroid hormone (PTH) secretion and urinary calcium (uCa) reabsorption in response to variations in blood calcium. The CaSR signals by coupling to G-proteins, including GNA11-encoded Gα11. The CLARIFY disease monitoring study [NCT05227287] is an ongoing global, multicenter, longitudinal, observational study to characterize disease burden, management, and progression in children and adults with ADH1/2 over a 5-year period. Of 25 pediatric participants (birth to <18y) enrolled (Mar 2022 to Jun 2024), 22 were diagnosed with ADH1 and 3 with ADH2; 64% are females. Median age at enrollment was 9 years (IQR 5-13). Median age at hypocalcemia presentation and ADH1/2 diagnosis were 0. 8 years (IQR 0. 0-3. 0) and 1. 0 year (IQR 0. 5-3. 0), respectively. Family history of ADH1/2 was reported in 64% of participants. 16 unique CASR and 2 unique GNA11 variants were present, with CASR E767K (3) and F788C (3) the most frequent. Treatment regimen varied at baseline (Day 1 study visit): 32% (8) were on Ca and active vitamin D, 24% (6) on Ca alone, 8% (2) on active vitamin D alone, 20% (5) on PTH replacement, 20% (5) on magnesium, 12% (3) on thiazide diuretics, 12% (3) on potassium, 12% (3) on phosphate binder, 32% (8) on cholecalciferol, and 20% (5) without treatment. At baseline, 92% (23) had hypocalcemia (0-<1y <2. 1 mmol/l; 1-17y <2. 15 mmol/l), 83% (20) had low iPTH (<15 ng/l), 84% (21) had hyperphosphatemia (0-<1y >2. 5 mmol/l; 1-12y >1. 9 mmol/l; 13-17y >1. 5 mmol/l), 8% (2) had hypomagnesemia (<0. 62 mmol/l), and 84% (21) had normal total 25-OH Vitamin D (50-125 nmol/l). 32% (6) of 19 participants with 24hr uCa collected were hypercalciuric (>0. 1 mmol/kg/day); and 0% of 5 participants with spot urine collections had Ca/Cr above the aged-defined reference range (7-18mo <1. 70 mmol/mmol; 19mo – 6y <1. 16 mmol/mmol; adults <0. 59 mmol/mmol). Baseline eGFR by Schwartz equation was 117±25 mL/min/1. 73m2 (range: 69-175). Common (proxy) self-reported ADH1-related comorbidities were seizures (36%), nephrocalcinosis (32%), dental abnormalities (20%), and long QT syndrome (16%). This study represents the largest pediatric cohort of ADH1/2 described to date. Persistent hypocalcemia and hypercalciuria, along with the high prevalence of comorbidities, highlights the ongoing medical need in this population. Long-term prospective data are needed to better understand disease progression and burden of ADH1/2.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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