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 | ||
==[[Familial hypocalciuric hypercalcemia pathophysiology|Pathophysiology]]== | ==[[Familial hypocalciuric hypercalcemia pathophysiology|Pathophysiology]]== | ||
The pathophysiology of [Familial hypocalciuric hypercalcemia] is due to an inactivating missense mutation in the calcium sensing receptor (CaSR) | 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. | ||
==[[Familial hypocalciuric hypercalcemia causes|Causes]]== | ==[[Familial hypocalciuric hypercalcemia causes|Causes]]== | ||
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Prenatal testing for FHH is not recommended routinely. | Prenatal testing for FHH is not recommended routinely. | ||
In both parents with type-1 FHH their offsprings are screened for CASR mutation | In both parents with type-1 FHH their offsprings are screened for CASR mutation. | ||
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 | 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. | ||
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.<ref name="pmid21697018">{{cite journal |vauthors=Fernández López I, Fernández Peña I, Cózar León MV, Viloria Peñas MM, Martínez De Pinillos Gordillo G, Fernández-Ladreda MT, Duran García S |title=[Usefulness of genetic tests in familial hypocalciuric hypercalcemia with atypical clinical presentation] |language=Spanish; Castilian |journal=Endocrinol Nutr |volume=58 |issue=7 |pages=325–30 |year=2011 |pmid=21697018 |doi=10.1016/j.endonu.2011.04.004 | 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.<ref name="pmid21697018">{{cite journal |vauthors=Fernández López I, Fernández Peña I, Cózar León MV, Viloria Peñas MM, Martínez De Pinillos Gordillo G, Fernández-Ladreda MT, Duran García S |title=[Usefulness of genetic tests in familial hypocalciuric hypercalcemia with atypical clinical presentation] |language=Spanish; Castilian |journal=Endocrinol Nutr |volume=58 |issue=7 |pages=325–30 |year=2011 |pmid=21697018 |doi=10.1016/j.endonu.2011.04.004 |url=}}</ref>. | ||
==[[Familial hypocalciuric hypercalcemia natural history, complications and prognosis|Natural History, Complications and Prognosis]]== | ==[[Familial hypocalciuric hypercalcemia natural history, complications and prognosis|Natural History, Complications and Prognosis]]== | ||
Revision as of 13:32, 18 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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American Roentgen Ray Society Images of Familial hypocalciuric hypercalcemia |
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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
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. 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. 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.[1].
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
- ↑ 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.