Clinical and outcome comparison of genetically positive vs. negative patients in a large cohort of suspected familial hypocalciuric hypercalcemia
Asla, Queralt (Institut d'Investigació Biomèdica Sant Pau)
Sardà, Helena (Universitat Autònoma de Barcelona. Departament de Medicina)
Seguí, Núria (Hospital Clínic i Provincial de Barcelona)
Martínez de Pinillos, Guillermo (Hospital Universitario Virgen de Valme (Sevilla, Andalusia))
Mazarico, Isabel (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Capel Flores, Ismael (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Rives Jimenez, José (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Suárez Balaguer, Javier (Hospital Arnau de Vilanova (València))
Ávila-Rubio, Verónica (Instituto de Investigación Biosanitaria de Granada)
Muñoz Torres, Manuel (Instituto de Salud Carlos III)
Saigí, Ignasi (Hospital Universitari de Vic)
Palacios, Nuria (Hospital Universitario Puerta de Hierro Majadahonda)
Urgell, Eulàlia (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Webb, S. M 1952- (Universitat Autònoma de Barcelona. Departament de Medicina)
Fernández, Mercè (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Oriola, Josep (Hospital Clínic i Provincial de Barcelona)
Mora, Mireia (Hospital Clínic i Provincial de Barcelona)
Tondo, Mireia (Institut d'Investigació Biomèdica Sant Pau)
Aulinas, Anna (Institut d'Investigació Biomèdica Sant Pau)

Date:	2023
Abstract:	Biochemical suspicion of familial hypocalciuric hypercalcemia (FHH) might provide with a negative (FHH-negative) or positive (FHH-positive) genetic result. Understanding the differences between both groups may refine the identification of those with a positive genetic evaluation, aid management decisions and prospective surveillance. We aimed to compare FHH-positive and FHH-negative patients, and to identify predictive variables for FHH-positive cases. Retrospective, national multi-centre study of patients with suspected FHH and genetic testing of the CASR, AP2S1 and GNA11 genes. Clinical, biochemical, radiological and treatment data were collected. We established a prediction model for the identification of FHH-positive cases by logistic regression analysis and area under the ROC curve (AUROC) was estimated. We included 66 index cases, of which 30 (45. 5%) had a pathogenic variant. FHH-positive cases were younger (p = 0. 029), reported more frequently a positive family history (p < 0. 001), presented higher magnesium (p < 0. 001) and lower parathormone levels (p < 0. 001) and were less often treated for hypercalcemia (p = 0. 017) in comparison to FHH-negative cases. Magnesium levels showed the highest AUROC (0. 825, 95%CI: 0. 709-0. 941). The multivariate analysis revealed that family history and magnesium levels were independent predictors of a positive genetic result. The predictive model showed an AUROC of 0. 909 (95%CI: 0. 826-0. 991). The combination of magnesium and a positive family history offered a good diagnostic accuracy to predict a positive genetic result. Therefore, the inclusion of magnesium measurement in the routine evaluation of patients with suspected FHH might provide insight into the identification of a positive genetic result of any of the CaSR-related genes.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Calcium disorders ; Calcium-sensing receptor (CaSR) ; CASR gene ; CASR mutations ; Familial hypocalciuric hypercalcemia (FHH) ; Primary hyperparathyroidism (PHPT)
Published in:	Endocrine, Vol. 83 (october 2023) , p. 747-756, ISSN 1559-0100

DOI: 10.1007/s12020-023-03560-y
PMID: 38214877

10 p, 1001.7 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles