PMID- 26646938
OWN - NLM
STAT- MEDLINE
DCOM- 20160809
LR  - 20161018
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Linking)
VI  - 174
IP  - 5
DP  - 2016 May
TI  - GENETICS IN ENDOCRINOLOGY: Gain and loss of function mutations of the 
      calcium-sensing receptor and associated proteins: current treatment concepts.
PG  - R189-208
LID - 10.1530/EJE-15-1028 [doi]
AB  - The calcium-sensing receptor (CASR) is the main calcium sensor in the maintenance 
      of calcium metabolism. Mutations of the CASR, the G protein alpha 11 (GNA11) and 
      the adaptor-related protein complex 2 sigma 1 subunit (AP2S1) genes can shift the 
      set point for calcium sensing causing hyper- or hypo-calcemic disorders. 
      Therapeutic concepts for these rare diseases range from general therapies of 
      hyper- and hypo-calcemic conditions to more pathophysiology oriented approaches 
      such as parathyroid hormone (PTH) substitution and allosteric CASR modulators. 
      Cinacalcet is a calcimimetic that enhances receptor function and has gained 
      approval for the treatment of hyperparathyroidism. Calcilytics in turn attenuate 
      CASR activity and are currently under investigation for the treatment of various 
      diseases. We conducted a literature search for reports about treatment of 
      patients harboring inactivating or activating CASR, GNA11 or AP2S1 mutants and 
      about in vitro effects of allosteric CASR modulators on mutated CASR. The 
      therapeutic concepts for patients with familial hypocalciuric hypercalcemia 
      (FHH), neonatal hyperparathyroidism (NHPT), neonatal severe hyperparathyroidism 
      (NSHPT) and autosomal dominant hypocalcemia (ADH) are reviewed. FHH is usually 
      benign, but symptomatic patients benefit from cinacalcet. In NSHPT patients 
      pamidronate effectively lowers serum calcium, but most patients require 
      parathyroidectomy. In some patients cinacalcet can obviate the need for surgery, 
      particularly in heterozygous NHPT. Symptomatic ADH patients respond to vitamin D 
      and calcium supplementation but this may increase calciuria and renal 
      complications. PTH treatment can reduce relative hypercalciuria. None of the 
      currently available therapies for ADH, however, prevent tissue calcifications and 
      complications, which may become possible with calcilytics that correct the 
      underlying pathophysiologic defect.
CI  - (c) 2016 European Society of Endocrinology.
FAU - Mayr, Bernhard
AU  - Mayr B
AD  - Division of Endocrinology and DiabetesDepartment of Medicine I, 
      Universitatsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 
      Ulmenweg 18, 91054 Erlangen, GermanyCenter for Chronic Sick ChildrenPediatric 
      Endocrinology and Diabetes, Charite University Medicine Berlin, Berlin, 
      GermanyDivision of Paediatric Endocrinology and DiabetesDepartment of 
      Paediatrics, Universitatsklinikum Erlangen, Friedrich-Alexander University 
      Erlangen-Nuremberg, Erlangen, Germany.
FAU - Schnabel, Dirk
AU  - Schnabel D
AD  - Division of Endocrinology and DiabetesDepartment of Medicine I, 
      Universitatsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 
      Ulmenweg 18, 91054 Erlangen, GermanyCenter for Chronic Sick ChildrenPediatric 
      Endocrinology and Diabetes, Charite University Medicine Berlin, Berlin, 
      GermanyDivision of Paediatric Endocrinology and DiabetesDepartment of 
      Paediatrics, Universitatsklinikum Erlangen, Friedrich-Alexander University 
      Erlangen-Nuremberg, Erlangen, Germany.
FAU - Dorr, Helmuth-Gunther
AU  - Dorr HG
AD  - Division of Endocrinology and DiabetesDepartment of Medicine I, 
      Universitatsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 
      Ulmenweg 18, 91054 Erlangen, GermanyCenter for Chronic Sick ChildrenPediatric 
      Endocrinology and Diabetes, Charite University Medicine Berlin, Berlin, 
      GermanyDivision of Paediatric Endocrinology and DiabetesDepartment of 
      Paediatrics, Universitatsklinikum Erlangen, Friedrich-Alexander University 
      Erlangen-Nuremberg, Erlangen, Germany.
FAU - Schofl, Christof
AU  - Schofl C
AD  - Division of Endocrinology and DiabetesDepartment of Medicine I, 
      Universitatsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 
      Ulmenweg 18, 91054 Erlangen, GermanyCenter for Chronic Sick ChildrenPediatric 
      Endocrinology and Diabetes, Charite University Medicine Berlin, Berlin, 
      GermanyDivision of Paediatric Endocrinology and DiabetesDepartment of 
      Paediatrics, Universitatsklinikum Erlangen, Friedrich-Alexander University 
      Erlangen-Nuremberg, Erlangen, Germany christof.schoefl@uk-erlangen.de.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20151208
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (AP2S1 protein, human)
RN  - 0 (Adaptor Protein Complex 2)
RN  - 0 (Adaptor Protein Complex sigma Subunits)
RN  - 0 (CASR protein, human)
RN  - 0 (GNA11 protein, human)
RN  - 0 (GTP-Binding Protein alpha Subunits)
RN  - 0 (Receptors, Calcium-Sensing)
SB  - IM
MH  - Adaptor Protein Complex 2/*genetics
MH  - Adaptor Protein Complex sigma Subunits/*genetics
MH  - GTP-Binding Protein alpha Subunits/*genetics
MH  - Humans
MH  - Hypercalcemia/*drug therapy/genetics
MH  - Hyperparathyroidism/*drug therapy/genetics
MH  - Hypocalcemia/*drug therapy/genetics
MH  - Receptors, Calcium-Sensing/*genetics
EDAT- 2015/12/10 06:00
MHDA- 2016/08/10 06:00
CRDT- 2015/12/10 06:00
PHST- 2015/10/19 00:00 [received]
PHST- 2015/12/08 00:00 [accepted]
PHST- 2015/12/10 06:00 [entrez]
PHST- 2015/12/10 06:00 [pubmed]
PHST- 2016/08/10 06:00 [medline]
AID - EJE-15-1028 [pii]
AID - 10.1530/EJE-15-1028 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2016 May;174(5):R189-208. doi: 10.1530/EJE-15-1028. Epub 2015 
      Dec 8.