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Familial hypocalciuric hypercalcemia(FHH)

MedGen UID:
369200
•Concept ID:
C1809471
•
Disease or Syndrome
Synonyms: Familial benign hypercalcemia; FHH
SNOMED CT: Familial benign hypercalcemia (237885008); Familial hypocalciuric hypercalcemia (237885008); FHH - familial hypocalciuric hypercalcemia (237885008)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (Orphanet)
 
Monarch Initiative: MONDO:0018458
OMIM® Phenotypic series: PS145980
Orphanet: ORPHA405

Definition

Familial hypocalciuric hypercalcemia (FHH) is a generally asymptomatic genetic disorder of phosphocalcic metabolism characterized by lifelong moderate hypercalcemia along with normo- or hypocalciuria and elevated plasma parathyroid hormone (PTH) concentration. [from ORDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFamilial hypocalciuric hypercalcemia

Professional guidelines

PubMed

Genetic testing for familial hyperparathyroidism: clinical-genetic profile in a Mediterranean cohort.
Mazarico-Altisent I, Capel I, Baena N, Bella-Cueto MR, Barcons S, Guirao X, Pareja R, Muntean A, Arsentales V, Caixàs A, Rigla M
Front Endocrinol (Lausanne) 2023;14:1244361. Epub 2023 Sep 21 doi: 10.3389/fendo.2023.1244361. PMID: 37810884Free PMC Article
European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders.
Bollerslev J, Rejnmark L, Zahn A, Heck A, Appelman-Dijkstra NM, Cardoso L, Hannan FM, Cetani F, Sikjær T, Formenti AM, Björnsdottir S, Schalin-Jantti C, Belaya Z, Gibb FW, Lapauw B, Amrein K, Wicke C, Grasemann C, Krebs M, Ryhänen EM, Makay O, Minisola S, Gaujoux S, Bertocchio JP, Hassan-Smith ZK, Linglart A, Winter EM, Kollmann M, Zmierczak HG, Tsourdi E, Pilz S, Siggelkow H, Gittoes NJ, Marcocci C, Kamenicky P; 2021 PARAT Working Group
Eur J Endocrinol 2022 Feb 1;186(2):R33-R63. Epub 2022 Jan 13 doi: 10.1530/EJE-21-1044. [Epub ahead of print] PMID: 34863037Free PMC Article
Hypercalcemia during pregnancy: management and outcomes for mother and child.
Appelman-Dijkstra NM, Ertl DA, Zillikens MC, Rjenmark L, Winter EM
Endocrine 2021 Mar;71(3):604-610. Epub 2021 Feb 5 doi: 10.1007/s12020-021-02615-2. PMID: 33544354Free PMC Article

Recent clinical studies

Etiology

European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders.
Bollerslev J, Rejnmark L, Zahn A, Heck A, Appelman-Dijkstra NM, Cardoso L, Hannan FM, Cetani F, Sikjær T, Formenti AM, Björnsdottir S, Schalin-Jantti C, Belaya Z, Gibb FW, Lapauw B, Amrein K, Wicke C, Grasemann C, Krebs M, Ryhänen EM, Makay O, Minisola S, Gaujoux S, Bertocchio JP, Hassan-Smith ZK, Linglart A, Winter EM, Kollmann M, Zmierczak HG, Tsourdi E, Pilz S, Siggelkow H, Gittoes NJ, Marcocci C, Kamenicky P; 2021 PARAT Working Group
Eur J Endocrinol 2022 Feb 1;186(2):R33-R63. Epub 2022 Jan 13 doi: 10.1530/EJE-21-1044. [Epub ahead of print] PMID: 34863037Free PMC Article
Hereditary Primary Hyperparathyroidism.
Newey PJ
Endocrinol Metab Clin North Am 2021 Dec;50(4):663-681. doi: 10.1016/j.ecl.2021.08.003. PMID: 34774240
Sporadic and hereditary primary hyperparathyroidism.
Pepe J, Cipriani C, Pilotto R, De Lucia F, Castro C, Lenge L, Russo S, Guarnieri V, Scillitani A, Carnevale V, D'Erasmo E, Romagnoli E, Minisola S
J Endocrinol Invest 2011 Jul;34(7 Suppl):40-4. PMID: 21985979
Hypercalcemia in children and adolescents.
Lietman SA, Germain-Lee EL, Levine MA
Curr Opin Pediatr 2010 Aug;22(4):508-15. doi: 10.1097/MOP.0b013e32833b7c23. PMID: 20601885Free PMC Article
Familial hypocalciuric hypercalcemia and other disorders with resistance to extracellular calcium.
Brown EM
Endocrinol Metab Clin North Am 2000 Sep;29(3):503-22. doi: 10.1016/s0889-8529(05)70148-1. PMID: 11033758

Diagnosis

Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism.
Minisola S, Arnold A, Belaya Z, Brandi ML, Clarke BL, Hannan FM, Hofbauer LC, Insogna KL, Lacroix A, Liberman U, Palermo A, Pepe J, Rizzoli R, Wermers R, Thakker RV
J Bone Miner Res 2022 Nov;37(11):2315-2329. Epub 2022 Oct 17 doi: 10.1002/jbmr.4665. PMID: 36245271Free PMC Article
Familial Hypocalciuric Hypercalcemia and Neonatal Severe Hyperparathyroidism.
Vannucci L, Brandi ML
Front Horm Res 2019;51:52-62. Epub 2018 Nov 19 doi: 10.1159/000491038. PMID: 30641521
Familial hypocalciuric hypercalcemia and related disorders.
Lee JY, Shoback DM
Best Pract Res Clin Endocrinol Metab 2018 Oct;32(5):609-619. Epub 2018 May 26 doi: 10.1016/j.beem.2018.05.004. PMID: 30449544Free PMC Article
Hypercalcemic Disorders in Children.
Stokes VJ, Nielsen MF, Hannan FM, Thakker RV
J Bone Miner Res 2017 Nov;32(11):2157-2170. Epub 2017 Nov 2 doi: 10.1002/jbmr.3296. PMID: 28914984Free PMC Article
A practical approach to hypercalcemia.
Carroll MF, Schade DS
Am Fam Physician 2003 May 1;67(9):1959-66. PMID: 12751658

Therapy

Cinacalcet therapy in a child with novel homozygous CASR p.Glu353Lys mutation causing familial hypocalciuric hypercalcemia type 1: case report and review of the literature.
Koca SB
Turk J Pediatr 2023;65(5):853-861. doi: 10.24953/turkjped.2022.1040. PMID: 37853976
Personalised medicines for familial hypercalcemia and hyperparathyroidism.
Josephs TM, Zhang F, Dinh LV, Keller AN, Conigrave AD, Capuano B, Gregory KJ, Leach K
J Mol Endocrinol 2022 May 9;69(1):243-257. doi: 10.1530/JME-21-0263. PMID: 35318962
Calcimimetic Use in Familial Hypocalciuric Hypercalcemia-A Perspective in Endocrinology.
Marx SJ
J Clin Endocrinol Metab 2017 Nov 1;102(11):3933-3936. doi: 10.1210/jc.2017-01606. PMID: 28945857Free PMC Article
Hypercalcemia in children and adolescents.
Lietman SA, Germain-Lee EL, Levine MA
Curr Opin Pediatr 2010 Aug;22(4):508-15. doi: 10.1097/MOP.0b013e32833b7c23. PMID: 20601885Free PMC Article
A practical approach to hypercalcemia.
Carroll MF, Schade DS
Am Fam Physician 2003 May 1;67(9):1959-66. PMID: 12751658

Prognosis

Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism.
Minisola S, Arnold A, Belaya Z, Brandi ML, Clarke BL, Hannan FM, Hofbauer LC, Insogna KL, Lacroix A, Liberman U, Palermo A, Pepe J, Rizzoli R, Wermers R, Thakker RV
J Bone Miner Res 2022 Nov;37(11):2315-2329. Epub 2022 Oct 17 doi: 10.1002/jbmr.4665. PMID: 36245271Free PMC Article
European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders.
Bollerslev J, Rejnmark L, Zahn A, Heck A, Appelman-Dijkstra NM, Cardoso L, Hannan FM, Cetani F, Sikjær T, Formenti AM, Björnsdottir S, Schalin-Jantti C, Belaya Z, Gibb FW, Lapauw B, Amrein K, Wicke C, Grasemann C, Krebs M, Ryhänen EM, Makay O, Minisola S, Gaujoux S, Bertocchio JP, Hassan-Smith ZK, Linglart A, Winter EM, Kollmann M, Zmierczak HG, Tsourdi E, Pilz S, Siggelkow H, Gittoes NJ, Marcocci C, Kamenicky P; 2021 PARAT Working Group
Eur J Endocrinol 2022 Feb 1;186(2):R33-R63. Epub 2022 Jan 13 doi: 10.1530/EJE-21-1044. [Epub ahead of print] PMID: 34863037Free PMC Article
Familial Hypocalciuric Hypercalcemia and Neonatal Severe Hyperparathyroidism.
Vannucci L, Brandi ML
Front Horm Res 2019;51:52-62. Epub 2018 Nov 19 doi: 10.1159/000491038. PMID: 30641521
Familial hypocalciuric hypercalcemia and related disorders.
Lee JY, Shoback DM
Best Pract Res Clin Endocrinol Metab 2018 Oct;32(5):609-619. Epub 2018 May 26 doi: 10.1016/j.beem.2018.05.004. PMID: 30449544Free PMC Article
A practical approach to hypercalcemia.
Carroll MF, Schade DS
Am Fam Physician 2003 May 1;67(9):1959-66. PMID: 12751658

Clinical prediction guides

Genetic testing for familial hyperparathyroidism: clinical-genetic profile in a Mediterranean cohort.
Mazarico-Altisent I, Capel I, Baena N, Bella-Cueto MR, Barcons S, Guirao X, Pareja R, Muntean A, Arsentales V, Caixàs A, Rigla M
Front Endocrinol (Lausanne) 2023;14:1244361. Epub 2023 Sep 21 doi: 10.3389/fendo.2023.1244361. PMID: 37810884Free PMC Article
Neurodevelopmental Abnormalities in Patients with Familial Hypocalciuric Hypercalcemia Type 3.
Chinoy A, Nicholson J, Skae M, Hannan FM, Thakker RV, Mughal MZ, Padidela R
J Pediatr 2023 Jun;257:113367. Epub 2023 Mar 2 doi: 10.1016/j.jpeds.2023.02.013. PMID: 36868303
Calcium homeostasis and hyperparathyroidism: Nephrologic and endocrinologic points of view.
Lemoine S, Figueres L, Bacchetta J, Frey S, Dubourg L
Ann Endocrinol (Paris) 2022 Aug;83(4):237-243. Epub 2022 May 19 doi: 10.1016/j.ando.2022.05.003. PMID: 35598638
European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders.
Bollerslev J, Rejnmark L, Zahn A, Heck A, Appelman-Dijkstra NM, Cardoso L, Hannan FM, Cetani F, Sikjær T, Formenti AM, Björnsdottir S, Schalin-Jantti C, Belaya Z, Gibb FW, Lapauw B, Amrein K, Wicke C, Grasemann C, Krebs M, Ryhänen EM, Makay O, Minisola S, Gaujoux S, Bertocchio JP, Hassan-Smith ZK, Linglart A, Winter EM, Kollmann M, Zmierczak HG, Tsourdi E, Pilz S, Siggelkow H, Gittoes NJ, Marcocci C, Kamenicky P; 2021 PARAT Working Group
Eur J Endocrinol 2022 Feb 1;186(2):R33-R63. Epub 2022 Jan 13 doi: 10.1530/EJE-21-1044. [Epub ahead of print] PMID: 34863037Free PMC Article
Familial Hypocalciuric Hypercalcemia Type 1 and Autosomal-Dominant Hypocalcemia Type 1: Prevalence in a Large Healthcare Population.
Dershem R, Gorvin CM, Metpally RPR, Krishnamurthy S, Smelser DT, Hannan FM, Carey DJ, Thakker RV, Breitwieser GE; Regeneron Genetics Center
Am J Hum Genet 2020 Jun 4;106(6):734-747. Epub 2020 May 7 doi: 10.1016/j.ajhg.2020.04.006. PMID: 32386559Free PMC Article

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