Inactivating calcium‐sensing receptor mutations in patients with primary hyperparathyroidism

Frank‐Raue, Karin; Leidig-Bruckner, G.; Haag, Christine; Schulze, Egbert; Lorenz, Angela; Schmitz‐Winnenthal, Hubertus; Raue, Friedhelm

doi:10.1111/j.1365-2265.2011.04059.x

Cited by 57 publications

(46 citation statements)

References 32 publications

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“…Moreover, the R990G variant of CaSR seems to be more common in the general Chinese population, but also in Chinese patients with hyperparathyroidism [15]. The coexistence of hyperparathyroidism and hypocalciuric hypercalcaemia syndrome was also identified in 4 out of 139 patients from a hyperparathyroid Caucasian population [16]. The serum calcium levels decreased postoperatively.…”

Section: Genetic Causesmentioning

confidence: 99%

Diseases associated with calcium-sensing receptor

Vahé

Benomar

Espiard

et al. 2017

Orphanet J Rare Dis

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The calcium-sensing receptor (CaSR) plays a pivotal role in systemic calcium metabolism by regulating parathyroid hormone secretion and urinary calcium excretion. The diseases caused by an abnormality of the CaSR are genetically determined or are more rarely acquired. The genetic diseases consist of hyper- or hypocalcemia disorders. Hypercalcaemia disorders are related to inactivating mutations of the CASR gene either heterozygous (autosomal dominant familial benign hypercalcaemia, still named hypocalciuric hypercalcaemia syndrome type 1) or homozygous (severe neonatal hyperparathyroidism). The A986S, R990G and Q1011E variants of the CASR gene are associated with higher serum calcium levels than in the general population, hypercalciuria being also associated with the R990G variant. The differential diagnosis consists in the hypocalciuric hypercalcaemia syndrome, types 2 (involving GNA11 gene) and 3 (involving AP2S1 gene); hyperparathyroidism; abnormalities of vitamin D metabolism, involving CYP24A1 and SLC34A1 genes; and reduced GFR. Hypocalcemia disorders, which are more rare, are related to heterozygous activating mutations of the CASR gene (type 1), consisting of autosomal dominant hypocalcemia disorders, sometimes with a presentation of pseudo-Bartter’s syndrome. The differential diagnosis consists of the hypercalciuric hypocalcaemia syndrome type 2, involving GNA11 gene and other hypoparathyroidism aetiologies. The acquired diseases are related to the presence of anti-CaSR antibodies, which can cause hyper- or especially hypocalcemia disorders (for instance in APECED syndromes), determined by their functionality. Finally, the role of CaSR in digestive, respiratory, cardiovascular and neoplastic diseases is gradually coming to light, providing new therapeutic possibilities. Two types of CaSR modulators are known: CaSR agonists (or activators, still named calcimimetics) and calcilytic antagonists (or inhibitors of the CasR). CaSR agonists, such as cinacalcet, are indicated in secondary and primary hyperparathyroidism. Calcilytics have no efficacy in osteoporosis, but could be useful in the treatment of hypercalciuric hypocalcaemia syndromes.

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Section: Genetic Causesmentioning

confidence: 99%

Diseases associated with calcium-sensing receptor

Vahé

Benomar

Espiard

et al. 2017

Orphanet J Rare Dis

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“…Further confusion between FHH and PHPT derives from recent reports of the development of classic parathyroid adenomas and symptomatic PHPT in some teens and adults with FHH, however. 38,39 …”

Section: Etiology Of Pediatric Phptmentioning

confidence: 99%

Primary hyperparathyroidism in children and adolescents

Roizen

Levine

2012

Journal of the Chinese Medical Association

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Primary hyperparathyroidism (PHPT) is a common endocrine disorder in adults in whom the typical presentation is incidentally discovered as asymptomatic hypercalcemia. PHPT is much less common in children and adolescents, but has greater morbidity in this age group, as most young patients with PHPT will have symptomatic hypercalcemia or complications such as kidney stones, abdominal pain, and skeletal fragility. An important feature of PHPT in younger patients is the relatively high prevalence of germline inactivating mutations of the CASR gene, which encodes the calcium-sensing receptor. Biallelic CASR mutations cause neonatal severe hyperparathyroidism, a life-threatening condition that presents within days of life with marked hypercalcemia, respiratory distress, failure to thrive, and skeletal demineralization. By contrast, more common heterozygous CASR mutations are generally associated with a benign variant of PHPT termed familial hypocalciuric hypercalcemia. Appropriate management of PHPT in children and adolescents requires distinction between familial hypocalciuric hypercalcemia, which generally requires no specific treatment, and other forms of PHPT that are best treated by parathyroidectomy.

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“…Nonetheless, it should be kept in mind that patients harboring inactivating mutations of the CASR gene and surgically proven PHPT (as demonstrated by normalization of hypercalcemia after surgery), have been described. These cases account for up to 3 % of PHPT patients [34].…”

Section: Is There a Role For Genetic Testing In A Patient With Mild Pmentioning

confidence: 99%

Italian Society of Endocrinology Consensus Statement: definition, evaluation and management of patients with mild primary hyperparathyroidism

Marcocci

Brandi

Scillitani

et al. 2015

J Endocrinol Invest

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Inactivating calcium‐sensing receptor mutations in patients with primary hyperparathyroidism

Abstract: The coexistence of HPT and FHH in four of 139 patients suggests a pathogenetic role of CaSR mutations in HPT. Despite also having a CaSR mutation, these patients benefited from parathyroid surgery.

Cited by 57 publications

References 32 publications

Diseases associated with calcium-sensing receptor

Diseases associated with calcium-sensing receptor

Primary hyperparathyroidism in children and adolescents

Italian Society of Endocrinology Consensus Statement: definition, evaluation and management of patients with mild primary hyperparathyroidism

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