Natural History, Diagnostic Pathway, and Treatment Patterns in Autosomal Dominant Hypocalcemia Type 1 (ADH1): Insights from the French Epi-Hypo Registry — ASN Events
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  2. CaSR-5 Session-7: Mineral Metabolism-2: CaSR and the kidney
  3. Natural History, Diagnostic Pathway, and Treatment Patterns in Autosomal Dominant Hypocalcemia Type 1 (ADH1): Insights from the French Epi-Hypo Registry

Natural History, Diagnostic Pathway, and Treatment Patterns in Autosomal Dominant Hypocalcemia Type 1 (ADH1): Insights from the French Epi-Hypo Registry (#214)

Jean-Philippe Bertocchio 1 , Caroline Prot-Bertoye 2 , Justine Bacchetta 3 , Sandrine Lemoine 3 , Aline Thomas 4 , Marie-Christine Vantyghem 5 , Anne Blanchard 2 , Peter Kamenicky 6 , Lise Criniere 7 , Morgane Gosselin 8 , Valérie Porquet-Bordes 9 , Severine Boqueho 10 , Emmanuel Letavernier 11 , Bertrand Knebelmann 12 , Agnès Linglart 6 , Pascal Houillier 2
  1. AP-HP - Hôpital de la Pitié-Salpêtrière, Paris, France
  2. AP-HP - European Geogres Pompidou Hospital, Paris, France
  3. HCL, Lyon, France
  4. SKEZI, Annecy, France
  5. CHRU Lille, Lille, France
  6. AP-HP - Kremlin-Bicêtre Hospital, Le Kremlin-Bicêtre, France
  7. CHRU Tours, Tours, France
  8. CHRU Brest, Brest, France
  9. CHU Toulouse, Toulouse, France
  10. Private office, Saint Junien, France
  11. AP-HP - Tenon hospital, Paris, France
  12. AP-HP - Necker Hospital, Paris, France

Autosomal Dominant Hypocalcemia Type 1 (ADH1), caused by activating CASR gene variants, is a rare genetic disorder classified among the rare causes of chronic hypoparathyroidism. Distinguishing ADH1 from post-surgery hypoparathyroidism (psurghypoPT) and other genetic causes of hypoparathyroidism is essential, as ADH1 has a distinct natural history that may impact medical decisions and long-term outcomes.

To characterize diagnostic latency, clinical/biochemical features, complications, and treatment patterns in genetically-confirmed ADH1 patients versus matched psurghypoPT controls.

This nested case-control study used data from the French Epi-Hypo registry (2016–present). ADH1 patients (n=46, 11 aged <18) were matched 1:2 with psurghypoPT controls (n=92) on age and sex. Data included baseline characteristics, follow-up (mean 8.0±8.4 years for ADH1), complications (nephrolithiasis/nephrocalcinosis, cataracts, and cerebral calcifications), biomarkers (calcium both in blood and in urine, and blood magnesium, phosphate, PTH concentrations), and treatments.

ADH1 patients had a significantly longer diagnostic latency (13.7±20.7 vs. 2.7±6.3 years, p<0.001) despite earlier age at symptoms onset (10.8±16.1 vs. 29.8±20.7 years, p<0.001). Family screening was more frequent in ADH1 (28% vs. 0%, p<0.001). ADH1 patients had higher rates of nephrolithiasis/nephrocalcinosis (47% vs. 19%, p=0.007) during follow-up. At last visit, blood total calcium (2.00±0.30 vs. 2.14±0.30 mmol/L, p=0.022) and magnesium (0.72±0.11 vs. 0.77±0.10 mmol/L, p=0.023) concentrations were lower in ADH1 patients while PTH ratio (0.28±0.21 vs. 0.26±0.16, p=0.70) and 24h-calcium excretion (4.25±2.39 vs. 4.70±3.00, p=0.40) showed no differences. Phosphatemia tended to be higher (1.50±0.45 vs. 1.35±0.34, p=0.067) in ADH1 patients. Treatment patterns showed no differences with calcium+active vitamin D being the most frequent (51%) regimen of treatment.

These results show that ADH1 is associated with delayed diagnosis, earlier onset, and distinct clinical/biochemical profiles compared to psurghypoPT. These findings highlight the importance of differentiating ADH1 for tailored management. This study should be expanded to a broader cohort of patients with ADH1.