Familial hypocalciuric hypercalcemia: Difference between revisions
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Three genetically heterogeneous variants are reported so far for familial hypocalciuric hypercalcemia. | Three genetically heterogeneous variants are reported so far for familial hypocalciuric hypercalcemia. | ||
Type 1 - due to loss-of-functional mutations of the calcium-sensing receptor (encoded by CASR). Type 2 - unknown cause. | Type 1 - due to loss-of-functional mutations of the calcium-sensing receptor (encoded by CASR). Type 2 - unknown cause. | ||
Type 3 - associated with adaptor-related protein complex 2, sigma 1 subunit (AP2S1) mutations, which alter calcium-sensing receptor endocytosis | Type 3 - associated with adaptor-related protein complex 2, sigma 1 subunit (AP2S1) mutations, which alter calcium-sensing receptor endocytosis<ref name="pmid1682230">{{cite journal |vauthors=Garioch JJ, Mackie RM, Campbell I, Forsyth A |title=Keratinocyte expression of intercellular adhesion molecule 1 (ICAM-1) correlated with infiltration of lymphocyte function associated antigen 1 (LFA-1) positive cells in evolving allergic contact dermatitis reactions |journal=Histopathology |volume=19 |issue=4 |pages=351–4 |year=1991 |pmid=1682230 |doi= |url=}}</ref><ref name="urlMutations Affecting G-Protein Subunit α11 in Hypercalcemia and Hypocalcemia — NEJM">{{cite web |url=http://www.nejm.org/doi/full/10.1056/NEJMoa1300253#t=article |title=Mutations Affecting G-Protein Subunit α11 in Hypercalcemia and Hypocalcemia — NEJM |format= |work= |accessdate=}}</ref> | ||
==[[Familial hypocalciuric hypercalcemia pathophysiology|Pathophysiology]]== | ==[[Familial hypocalciuric hypercalcemia pathophysiology|Pathophysiology]]== | ||
Revision as of 17:59, 15 September 2017
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Familial hypocalciuric hypercalcemia Microchapters |
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Differentiating Familial Hypocalciuric Hypercalcemia from other Diseases |
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Diagnosis |
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Treatment |
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Case Studies |
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Familial hypocalciuric hypercalcemia On the Web |
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Risk calculators and risk factors for Familial hypocalciuric hypercalcemia |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ajay Gade MD[2]]
Synonyms and keywords:
Overview
Historical Perspective
Classification
Three genetically heterogeneous variants are reported so far for familial hypocalciuric hypercalcemia. Type 1 - due to loss-of-functional mutations of the calcium-sensing receptor (encoded by CASR). Type 2 - unknown cause. Type 3 - associated with adaptor-related protein complex 2, sigma 1 subunit (AP2S1) mutations, which alter calcium-sensing receptor endocytosis[1][2]
Pathophysiology
The pathophysiology of [Familial hypocalciuric hypercalcemia] is due to an inactivating missense mutation in the calcium sensing receptor (CaSR) located on the short arm of the chromosome 3 (FBHH3q). The mutation of CaSR is associated with two inherited conditions FBHH and neonatal hyperparathyroidism. CaSR is a plasma membrane G protein coupled receptor which is expressed on the chief cells of the parathyroid glands and the cells lining the renal tubules. CasR has the ability to sense any changes in the circulating calcium concentrated and send this information through the signaling pathway to the Parathyroid gland that modifies the PTH secretion.
Causes
Differentiating Xyz from other Diseases
Familial hypocalciuric hypercalcemia should be differentiated from other causes of hypercalcemia. Causes of hypercalcemia include:
Parathyroid-related
Hyperparathyroidism
Primary hyperparathyroidism
Secondary hyperparathyroidism
Tertiary hyperparathyroidism
Familial hypocalciuric hypercalcemia
Non-parathyroid related
Malignancy
Humoral hypercalcemia of malignancy
Osteolytic tumors
Production of calcitriol by tumors
Ectopic parathyroid hormone production
Medication-induced
Thiazide diuretics
Lithium
Nutritional
Milk-alkali syndrome
Vitamin D toxicity
Granulomatous disease
Sarcoidosis
Surgical
Immobilization
Epidemiology and Demographics
Risk Factors
Screening
Prenatal testing for FHH is not recommended routinely. In both parents with type-1 FHH their offsprings are screened for CASR mutation[3]. Genetic screening for the CASR familial mutation is also offered to family members of affected individuals, CaSR and AP2S1 sequencing is done in patients with familial hyperparathyroidism and phenotype suggesting FHH. GNA11 mutations seem much rarer. Learning disabilities in these patients, associated with higher serum calcium and magnesium levels may suggest the presence of AP2S1 rather than CaSR mutation and may guide the first step in the genetic evaluation.[3][4].
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms | Physical Examination | Electrocardiogram | Laboratory Findings | X-Ray Findings | Echocardiography and Ultrasound | CT-Scan Findings | MRI Findings | Other Diagnostic Studies | Other Imaging Findings
Treatment
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case Studies
- ↑ Garioch JJ, Mackie RM, Campbell I, Forsyth A (1991). "Keratinocyte expression of intercellular adhesion molecule 1 (ICAM-1) correlated with infiltration of lymphocyte function associated antigen 1 (LFA-1) positive cells in evolving allergic contact dermatitis reactions". Histopathology. 19 (4): 351–4. PMID 1682230.
- ↑ "Mutations Affecting G-Protein Subunit α11 in Hypercalcemia and Hypocalcemia — NEJM".
- ↑ 3.0 3.1 Fernández López I, Fernández Peña I, Cózar León MV, Viloria Peñas MM, Martínez De Pinillos Gordillo G, Fernández-Ladreda MT, Duran García S (2011). "[Usefulness of genetic tests in familial hypocalciuric hypercalcemia with atypical clinical presentation]". Endocrinol Nutr (in Spanish; Castilian). 58 (7): 325–30. doi:10.1016/j.endonu.2011.04.004. PMID 21697018.
- ↑ Szalat A, Shpitzen S, Tsur A, Zalmon Koren I, Shilo S, Tripto-Shkolnik L, Durst R, Leitersdorf E, Meiner V (2017). "Stepwise CaSR, AP2S1, and GNA11 sequencing in patients with suspected familial hypocalciuric hypercalcemia". Endocrine. 55 (3): 741–747. doi:10.1007/s12020-017-1241-5. PMID 28176280.