French national reference center for rare diseases of calcium and phosphate metabolism

The constitutive reference center for rare diseases of calcium and phosphate metabolism at the Georges-Pompidou European hospital, coordinated by Pr Pascal Houillier, is an expert structure for rare diseases of calcium and phosphate metabolism (CAP) and their evolution throughout the life of an individual. The center includes : a day hospital for the diagnosis and follow-up of patients, their diseases and treatments, a specialized medical consultation, a bone densitometry unit, a genetic consultation, a laboratory specialized in hormonology (molecular diagnosis and specialized biology). The different activities are divided into 3 departments: the physiology department, the genetics department and the clinical investigation center.

The CAP-HEGP multidisciplinary team (physicians, biologists, nurses, dietician) is in charge of the clinical management and therapeutic education of patients and their families. The professionals are trained in the specificity of rare calcium and phosphate diseases. The professionals are trained in the specificity of rare calcium and phosphate diseases. The center has established local functional links with the psychology, radiology, cardiology and urology departments. Other specialties of recourse are represented in the establishment (AP-HP): dentist/parodontist/orthodontist at the Bretonneau hospital, adult rheumatology at the Cochin hospital, orthopedics at the Cochin hospital.

This reference center is affiliated with the OSCAR rare diseases healthcare network and the Endo-ERN (European Reference Network on rare endocrine conditions).

Keywords: Hypocalcemia, hypercalcemia, hyperparathyroidism, hypoparathyroidism, pseudohypoparathyroidism, hypophosphatemia, phosphate diabetes, oncogenic osteomalacia, hypophosphatemic osteomalacia, tumoral calcinosis, parathyroid hormone, vitamin D, hypomagnesemia, hypermagnesemia.

Medical team

Pr Pascal Houillier
MD, PhD

Contact us

Phone. +33 (0)1 56 09 39 69
or +33 (0)1 56 09 56 25

> Send an email

Please prefer to contact us by e-mail, and specify whether you are referred by a doctor or if you are contacting the center on your own because you have a rare disease.

In case of emergency

Missions of the center

The missions of the center are :

to reduce diagnostic wandering and improve the patient pathway :
- improvement of regional and national visibility of access to care :
  - information leaflets (with patient associations)
  - participation in the writing and editing of books :
    1. Pathologies phosphocalciques et osseuses de l’enfant Ed. Progrès en Pediatrie 2015,
    2. Approach to the patient with hypocalcemia, Oxford textbook of clinical nephrology, Oxford UP, 2016 (P. Houillier, section editor)
    3. Magnesium homeostasis, Oxford textbook of clinical nephrology, Oxford UP, 2016 (P. Houillier, section editor)
    4. Disorders of Calcium, Phosphate, and Magnesium Metabolism, Comprehensive Clinical Nephrology, Elsevier, 2017
  - lectures at numerous Days, Congresses and Conferences
- tools to improve access to diagnosis, recourse and appropriate therapy :
  - monthly multidisciplinary consultation meetings (RCP) and participation in the RCP of the reference center in secure webex (Lync) for diagnostic and therapeutic advice
  - structuring of molecular diagnosis by panel of phosphocalcic genes in ‘Next Generation Sequencing’ (NGS) [R. Vargas-Poussou’s molecular genetics laboratory; M.O. North’s molecular oncogenetics laboratory] ;
  - protocols of explorations specific to the pathologies of the reference center
- improving the transition from child to adult care
- actions in partnership with patient associations
to continue the description of new diseases and the phenotypic description of already known rare diseases
to develop innovative therapeutics
- investigator of therapeutic trials (human recombinant PTH),
- initiator of trials with new molecules (treatment of hypoparathyroidism);
- research methodology specific to rare diseases, integration of patient associations in the research process.

Pathologies

Syndromes causing hypercalcemia

Familial primary hyperparathyroidism
Primary hyperparathyroidism of genetic origin
Familial isolated hyperparathyroidism
Hyperparathyroidism-jaw tumor syndrome
Familial hypocalciuric hypercalcemia
Benign familial hypercalcemia type 1, type 2, type 3

Syndromes causing hypocalcaemia

Syndromes causing hypophosphataemia

Syndromes causing hyperphosphataemia

Familial hyperphosphatemic tumoral calcinosis/Hyperphosphatemic hyperostosis syndrome

Syndromes causing hypomagnesemia

Reference center team

Pr Pascal Houillier – Nephrologist, Head of the reference center
Pr Marie Courbebaisse – Nephrologist
Dr Gérard Maruani – Endocrinologist
Dr Arthur Michon-Colin – Nephrologist
Dr Mélanie Brunel – Nephrologist
Dr Caroline Prot-Bertoye – Nephrologist
Dr Anne Blanchard – Nephrologist
Dr Rosa Vargas-Poussou – Geneticist
Dr Stéphanie Baron – Biologist
Dr Simon Travers Allard – Biologist
Randa Rjab – Clinical research associate
Armelle Jourry – Medical-administrative assistant
Océane Hu-Shen – Medical-administrative assistant

Laura Poli – Dietician
Dominique Bara – Nurse
Nathalie Geoffroy – Nurse
Anne-Sophie Guillemet – Nurse
Valérie Nobre – Nurse
Nathalie Sauvat – Nurse
Aurelia Letienne – Caregiver
Laurence Baffalie – Laboratory technician
Christelle Bezia – Laboratory technician
Sabira Deshaies – Laboratory technician
Aurore Kling – Laboratory technician
Jonathan Ramahefasolo – Laboratory technician
Nathalie Reveilleau – Laboratory technician

National diagnostic and care protocols (PNDS)

Hypoparathyroidism PNDS (2017)
Hypophosphatemic rickets PNDS (2018)

Main current research studies and Education

RESEARCH

ANR T-Just – INSERM UMR_S1138 (Ongoing)
Epi-Hypo (Ongoing)
ACTICAS – Centre d’investigations cliniques (Currently being finalised)
Study of the role of the Claudin-19 protein -INSERM UMR_S1138 (Ongoing)
Effects of acute hypercalcaemic episodes on renal function – INSERM UMR_S1138 (Ongoing)
Cohort
Epi-Hypo – Over 1000 patients included

EDUCATION

Urinary lithiasis UD
Sorbonne university
Medical Bone Pathologies IUD
Paris university
Endocrine tumours IUD
Paris Saclay university
Constitutional Bone Diseases IUD
Paris university
Physiopathological approach to hydroelectrolytic disorders IUD
Sorbonne university

Publications

2022

– Practice patterns for chronic hypoparathyroidism: data from patients and physicians in France.
Bertocchio JP, Grosset N, Groussin L, Kamenicky P, Larceneux F, Lienhardt-Roussie A, Linglart A, Maruani G, Mirallie E, Pattou F, Seervai RNH, Sido C, Silve C, Vilfaillot A, Tabarin A, Vantyghem MC, Houillier P.
Endocr Connect. 2022 Jan 1:EC-21-0350.R2. doi: 10.1530/EC-21-0350. Epub ahead of print. PMID: 34939939.

2021

– The PARADIGHM (physicians advancing disease knowledge in hypoparathyroidism) registry for patients with chronic hypoparathyroidism: study protocol and interim baseline patient characteristics.
Gittoes N, Rejnmark L, Ing SW, Brandi ML, Björnsdottir S, Hahner S, Hofbauer LC, Houillier P, Khan AA, Levine MA, Mannstadt M, Shoback DM, Vokes TJ, Zhang P, Marelli C, Germak J, Clarke BL.
BMC Endocr Disord. 2021 Nov 20;21(1):232. doi: 10.1186/s12902-021-00888-2. PMID: 34801015; PMCID: PMC8606089.

– Gitelman-Like Syndrome Caused by Pathogenic Variants in mtDNA.
Viering D, Schlingmann KP, Hureaux M, Nijenhuis T, Mallett A, Chan M, van Beek A, van Eerde A, Coulibaly JM, Vallet M, Decramer S, Pelletier S, Klaus G, Kömhoff M, Beetz R, Patel C, Shenoy M, Steenbergen E, Anderson G, Bongers E, Bergmann C, Panneman D, Rodenburg R, Kleta R, Houillier P, Konrad M, Vargas-Poussou R, Knoers N, Bockenhauer D, de Baaij J.
J Am Soc Nephrol. 2021 Oct 4:ASN.2021050596. doi: 10.1681/ASN.2021050596. Epub ahead of print. PMID: 34607911.

– mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy.
Schlingmann KP, Jouret F, Shen K, Nigam A, Arjona FJ, Dafinger C, Houillier P, Jones DP, Kleinerüschkamp F, Oh J, Godefroid N, Eltan M, Güran T, Burtey S, Parotte MC, König J, Braun A, Bos C, Ibars Serra M, Rehmann H, Zwartkruis FJT, Renkema KY, Klingel K, Schulze-Bahr E, Schermer B, Bergmann C, Altmüller J, Thiele H, Beck BB, Dahan K, Sabatini D, Liebau MC, Vargas-Poussou R, Knoers NVAM, Konrad M, de Baaij JHF.
J Am Soc Nephrol. 2021 Nov;32(11):2885-2899. doi: 10.1681/ASN.2021030333. Epub 2021 Oct 4. PMID: 34607910.

– Biochemical assessment of phosphate homeostasis.
Houillier P, Salles JP.
Arch Pediatr. 2021 Oct;28(7):588-593. doi: 10.1016/j.arcped.2021.09.001. Epub 2021 Sep 28. PMID: 34598836.

– Differential localization patterns of claudin 10, 16, and 19 in human, mouse, and rat renal tubular epithelia.
Prot-Bertoye C, Griveau C, Skjødt K, Cheval L, Brideau G, Lievre L, Ferriere E, Arbaretaz F, Garbin K, Zamani R, Marcussen N, Figueres L, Breiderhoff T, Muller D, Bruneval P, Houillier P, Dimke H. Differential localization patterns of claudin 10, 16, and 19 in human, mouse, and rat renal tubular epithelia.
Am J Physiol Renal Physiol. 2021 Aug 1;321(2):F207-F224. doi: 10.1152/ajprenal.00579.2020. Epub 2021 Jun 21. PMID: 34151590; PMCID: PMC8424667.

– Challenges in the management of tumor-induced osteomalacia (TIO).
Brandi ML, Clunie GPR, Houillier P, Jan de Beur SM, Minisola S, Oheim R, Seefried L.
Bone. 2021 Nov;152:116064. doi: 10.1016/j.bone.2021.116064. Epub 2021 Jun 18. PMID: 34147708.

– Renal complications in patients with chronic hypoparathyroidism on conventional therapy: a systematic literature review : Renal disease in chronic hypoparathyroidism.
Gosmanova EO, Houillier P, Rejnmark L, Marelli C, Bilezikian JP.
Rev Endocr Metab Disord. 2021 Jun;22(2):297-316. doi: 10.1007/s11154-020-09613-1. Epub 2021 Feb 18

– Defects in KCNJ16 Cause a Novel Tubulopathy with Hypokalemia, Salt Wasting, Disturbed Acid-Base Homeostasis, and Sensorineural Deafness.
Schlingmann KP, Renigunta A, Hoorn EJ, Forst AL, Renigunta V, Atanasov V, Mahendran S, Barakat TS, Gillion V, Godefroid N, Brooks AS, Lugtenberg D, Lake J, Debaix H, Rudin C, Knebelmann B, Tellier S, Rousset-Rouvière C, Viering D, de Baaij JHF, Weber S, Palygin O, Staruschenko A, Kleta R, Houillier P, Bockenhauer D, Devuyst O, Vargas-Poussou R, Warth R, Zdebik AA, Konrad M.
J Am Soc Nephrol. 2021 Jun 1;32(6):1498-1512. doi: 10.1681/ASN.2020111587. Epub 2021 Apr 2. PMID: 33811157; PMCID: PMC8259640.

– Monitoring acid base status in CKD patients: can urinary citrate help?
Caroline Prot-Bertoye, Marion Vallet, Pascal Houillier
Kidney Int, 2021 Jan, PMID: 33390237 DOI: 10.1016/j.kint.2020.09.023

– When a maternal heterozygous mutation of the CYP24A1 gene leads to infantile hypercalcemia through a maternal uniparental disomy of chromosome 20.
Marguerite Hureaux, Sandra Chantot-Bastaraud, Kévin Cassinari, Edouard Martinez Casado, Ariane Cuny, Thierry Frébourg, Rosa Vargas-Poussou, Anne-Claire Bréhin
Mol Cytogenet, 2021 May 5, PMID: 33952337 PMCID: PMC8101107 DOI: 10.1186/s13039-021-00543-4

– Drug-Related Hypercalcemia.
Anne-Lise Lecoq, Marine Livrozet, Anne Blanchard, Peter Kamenický
Endocrinol Metab Clin North Am, 2021 Dec, PMID: 34774245 DOI: 10.1016/j.ecl.2021.08.001

– Primary Hyperparathyroidism in Homozygous Sickle Cell Patients: A Hemolysis-Mediated Hypocalciuric Hypercalcemia Phenotype?
Edmat Akhtar Khan, Lynda Cheddani, Camille Saint-Jacques, Rosa Vargas-Poussou, Vincent Frochot, Remi Chieze, Emmanuel Letavernier, Virginie Avellino, Francois Lionnet, Jean-Philippe Haymann
J Clin Med, 2021 Nov 5, PMID: 34768698 PMCID: PMC8584729 DOI: 10.3390/jcm10215179

2020

– Performance of ion chromatography to measure picomole amounts of magnesium in nanolitre samples.
Lucile Figueres, Caroline Prot-Bertoye, Luciana Morla, Elsa Ferriere, Camille Griveau, Gaëlle Brideau, Stéphanie Baron, Pascal Houillier
J Physiol, 2020 Dec, PMID: 32936928 DOI: 10.1113/JP280304

– Claudins in Renal Physiology and Pathology.
Caroline Prot-Bertoye, Pascal Houillier
Genes (Basel), 2020 Mar 10, PMID: 32164158 PMCID: PMC7140793 DOI: 10.3390/genes11030290

– Medullary and cortical thick ascending limb: similarities and differences.
Lise Bankir, Lucile Figueres, Caroline Prot-Bertoye, Nadine Bouby, Gilles Crambert, J Howard Pratt 5, Pascal Houillier
Am J Physiol Renal Physiol, 2020 Feb 1, PMID: 31841389 DOI: 10.1152/ajprenal.00261.2019

– FGF23 measurement in burosumab-treated patients: an emerging treatment may induce a new analytical interference.
Marie-Liesse Piketty, Severine Brabant, Jean-Claude Souberbielle, Gérard Maruani, Christelle Audrain, Anya Rothenbuhler, Dominique Prié, Agnès Linglart
Clin Chem Lab Med, 2020 Oct 25, PMID: 32653872 DOI: 10.1515/cclm-2020-0460

– Clinical characteristics of familial hypocalciuric hypercalcaemia type 1: A multicentre study of 77 adult patients.
Céline Mouly, Rosa Vargas-Poussou, Anne Lienhardt, Caroline Silve, Marguerite Hureaux, Corinne Magdelaine, Alexandre Buffet, Solange Grunenwald, Jean-Marc Kuhn, Thierry Brue, Yves Reznik, Antoine Tabarin, Dominique Martin-Coignard, Jean-Philippe Haymann, Ivan Tack, Antoine Bennet, Philippe Caron, Agnès Linglart, Delphine Vezzosi for the Reference Centre for Rare Diseases of Calcium, Phosphate Metabolism
Clin Endocrinol (Oxf), 2020 Sep, PMID: 32347971 DOI: 10.1111/cen.14211

– Tocilizumab in symptomatic calcium pyrophosphate deposition disease: a pilot study.
Augustin Latourte, Hang-Korng Ea, Aline Frazier, Anne Blanchard, Frédéric Lioté, Hubert Marotte, Thomas Bardin, Pascal Richette
Ann Rheum Dis, 2020 Aug, PMID: 32213498 DOI: 10.1136/annrheumdis-2020-217188

– Hyperparathyroidism in Patients With X-Linked Hypophosphatemia.
Anne-Lise Lecoq, Philippe Chaumet-Riffaud, Anne Blanchard, Margot Dupeux, Anya Rothenbuhler, Benoit Lambert, Emmanuel Durand, Erika Boros, Karine Briot, Caroline Silve, Bruno Francou, Marie Piketty, Philippe Chanson, Sylvie Brailly-Tabard, Agnès Linglart, Peter Kamenický
J Bone Miner Res, 2020 Jul, PMID: 32101626 DOI: 10.1002/jbmr.3992

2019

– Resistance to Insulin in Patients with Gitelman Syndrome and a Subtle Intermediate Phenotype in Heterozygous Carriers: A Cross-Sectional Study.
Blanchard, A ; Vallet, M ; Dubourg, L ; Hureaux, M ; Allard, J ; Haymann, JP & al
J Am Soc Nephrol, 2019 Aug, PMID: 31285285 PMCID: PMC6683723 DOI: 10.1681/ASN.2019010031

– Urinary citrate: helpful to predict acid retention in CKD patients?
Prot-Bertoye, C ; Vallet, M ; Houillier, P
Kidney Int, 2019 May, PMID: 31010475 DOI: 10.1016/j.kint.2019.01.019

– Response to Letter to the Editor: \ »Pro-FHH: A Risk Equation to Facilitate the Diagnosis of Parathyroid-Related Hypercalcemia\ ».
Bertocchio, JP ; Houillier, P
J Clin Endocrinol Metab, 2019 Feb 1, PMID: 30383233 DOI: 10.1210/jc.2018-02279

– High-throughput sequencing contributes to the diagnosis of tubulopathies and familial hypercalcemia hypocalciuria in adults.
Hureaux, M ; Ashton, E ; Dahan, K ; Houillier, P ; Blanchard, A ; Cormier, C & al
Kidney Int, 2019 Dec, PMID: 31672324 DOI: 10.1016/j.kint.2019.08.027

– Adverse events associated with currently used medical treatments for cystinuria and treatment goals: results from a series of 442 patients in France.
Prot-Bertoye, C ; Lebbah, S ; Daudon, M ; Tostivint, I ; Jais, JP ; Lillo-Le Louët, A & al
BJU Int, 2019 Nov, PMID: 30801923 DOI: 10.1111/bju.14721

– Treatment and long-term outcome in primary distal renal tubular acidosis.
Lopez-Garcia, SC ; Emma, F ; Walsh, SB ; Fila, M ; Hooman, N ; Zaniew, M & al
Nephrol Dial Transplant, 2019 Jun 1, PMID: 30773598 DOI: 10.1093/ndt/gfy409

2018

– Diagnosis and Management of Hyperparathyroidism.
Bertocchio, JP
Adv Surg, 2018 Sep, PMID: 30098609 DOI: 10.1016/j.yasu.2018.03.006

– The excretion of uromodulin is modulated by the calcium-sensing receptor.
Tokonami N, Olinger E, Debaix H, Houillier P, Devuyst O.
Kidney Int. 2018 Nov;94(5):882-886. doi: 10.1016/j.kint.2018.07.022.

– Pro-FHH: A Risk Equation to Facilitate the Diagnosis of Parathyroid-Related Hypercalcemia.
Bertocchio JP, Tafflet M, Koumakis E, Maruani G, Vargas-Poussou R, Silve C, Nissen PH, Baron S, Prot-Bertoye C, Courbebaisse M, Souberbielle JC, Rejnmark L, Cormier C, Houillier P.
J Clin Endocrinol Metab. 2018 Jul 1;103(7):2534-2542. doi: 10.1210/jc.2017-02773.

– Claudins: a tale of interactions in the thick ascending limb.
Olinger E, Houillier P, Devuyst O.
Kidney Int. 2018 Mar;93(3):535-537. doi: 10.1016/j.kint.2017.09.032.

– Multiplex epithelium dysfunction due to CLDN10 mutation: the HELIX syndrome.
Hadj-Rabia S, Brideau G, Al-Sarraj Y, Maroun RC, Figueres ML, Leclerc-Mercier S, Olinger E, Baron S, Chaussain C, Nochy D, Taha RZ, Knebelmann B, Joshi V, Curmi PA, Kambouris M, Vargas-Poussou R, Bodemer C, Devuyst O, Houillier P, El-Shanti H.
Genet Med. 2018 Feb;20(2):190-201. doi: 10.1038/gim.2017.71. Epub 2017 Aug 3.

2017

– Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis.
Bardet C, Ribes S, Wu Y, Diallo MT, Salmon B, Breiderhoff T, Houillier P, Müller D, Chaussain C.
Front Physiol. 2017 May 24;8:326. doi: 10.3389/fphys.2017.00326. eCollection 2017.

– Common variants in CLDN14 are associated with differential excretion of magnesium over calcium in urine.
Corre T, Olinger E, Harris SE, Traglia M, Ulivi S, Lenarduzzi S, Belge H, Youhanna S, Tokonami N, Bonny O, Houillier P, Polasek O, Deary IJ, Starr JM, Toniolo D, Gasparini P, Vollenweider P, Hayward C, Bochud M, Devuyst O.
Pflugers Arch. 2017 Jan;469(1):91-103. doi: 10.1007/s00424-016-1913-7. Epub 2016 Dec 3.

Participation in scientific events

Disorders of calcium and magnesium/Budapest P. Houillier/ Néphrologues
Calcium homeostasis and the kidney/ Londres/P. Houillier/ Néphrologues, réanimateurs, internistes
Les acteurs de l’homéostasie calcique : ce que nous devons connaitre en 2019/Paris/ P. Houillier/ Endocrinologues
ASN Kidney week Claudin 16-independent effect of parathyroid hormone (PTH) and calcium sensing-receptor (CaSR) on divalent cations reabsorption in the cortical thick ascending limb/ Washington DC/Caroline Prot-Bertoye
Diagnostic et prise en charge de l’hypoparathyroïdie/ Nancy/P. Houillier/Néphrologues
TJ-train Meeting/Berlin/P. Houillier/ Médecins, pharmaciens, scientifiques