Beneficial effect of cinacalcet in a child with familial hypocalciuric hypercalcemia

Alon, Uri; VanDeVoorde, René G.

doi:10.1007/s00467-010-1547-5

Cited by 52 publications

(27 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, calcimimetics have been proposed as a treatment option for NSHPT that could prevent the need for surgery [7,9,10,11]. We present a case of NSHPT that resulted from a homozygously inherited mutation that has not been previously described.…”

Section: Introductionmentioning

confidence: 87%

See 1 more Smart Citation

Neonatal Hypercalcemia due to a Homozygous Mutation in the Calcium-Sensing Receptor: Failure of Cinacalcet

Soblechero¹,

Castillo

Crespo

et al. 2013

Neonatology

View full text Add to dashboard Cite

A neonate affected by a novel inactivating mutation in the calcium-sensing receptor (CASR) gene is presented. This mutation is homozygously inherited and has not been previously described. A deletion in exon 5 (c.1392_1404del13) of the gene causes a loss of function of the receptor, which results in neonatal severe hyperparathyroidism and an ensuing extreme hypercalcemia. In a case of homozygosis of the CASR gene, the use of cinacalcet is the second reported calcimimetic treatment attempt and the first treatment attempt prior to surgery. However, because of the type of mutation, parathyroid surgery was necessary at 4 months of age after therapeutic failure. Because there are multiple mutations that affect the CASR gene in different ways, treatment with cinacalcet as an alternative to surgery may be valuable in homozygous cases that are caused by different mutations than the reported case.

show abstract

Section: Introductionmentioning

confidence: 87%

“…The CASR gene is encoded in the long arm of chromosome 3 [6], and there are more than 250 described mutations that affect CASR function (available at http://www.casrdb.mcgill.ca). The type of mutation can affect the severity of the clinical manifestations and the response to treatment [7,8]. …”

Section: Introductionmentioning

confidence: 99%

Neonatal Hypercalcemia due to a Homozygous Mutation in the Calcium-Sensing Receptor: Failure of Cinacalcet

Soblechero¹,

Castillo

Crespo

et al. 2013

Neonatology

View full text Add to dashboard Cite

show abstract

“…Two reports studied the dynamics of calcium and PTH after a single oral dose of cinacalcet in FHH type 1 patients. A significant decrease of PTH was detected as early as 2 h and effects on serum calcium were seen 8-48 h after the administration of cinacalcet (59,62,63). If clinically relevant the rapid effect of cinacalcet on PTH may be used to quickly assess the effectiveness of cinacalcet in individual patients (see below).…”

Section: Casr As a Drug Target For Allosteric Modulatorsmentioning

confidence: 99%

GENETICS IN ENDOCRINOLOGY: Gain and loss of function mutations of the calcium-sensing receptor and associated proteins: current treatment concepts

Mayr¹,

Schnabel²,

Dörr³

et al. 2016

European Journal of Endocrinology

View full text Add to dashboard Cite

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.

show abstract

“…The safety and efficacy of Cinacalcet in children has been shown in a few small series and anecdotal cases of secondary hyperparathyroidism in other disorders. (9)(10)(11)(12) .…”

Section: Discussionmentioning

confidence: 99%

“…(8) Preliminary studies showed the calcimimetic Cinacalcet to be safe and effective therapy in children with secondary hyperparathyroidism, as a result of other conditions, such as renal failure, X-linked hypophosphatemic rickets (XLH), and familial hypocalciuric hypercalcemia. (9)(10)(11)(12) In this report, we describe our novel experience with Cinacalcet therapy in a child with HVDRR that is resistant to 1,25(OH) 2 -D 3 , as a result of a missense mutation affecting the DNA-binding domain of VDR, in which all other modes of therapy were exhausted.…”

Section: H Ereditary Vitamin D-resistant Rickets (Hvdrr) Is a Rare Aumentioning

confidence: 99%

Cinacalcet as adjunctive therapy for hereditary 1,25-dihydroxyvitamin D–resistant rickets

Srivastava

Alon

2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Secondary hyperparathyroidism from inadequate calcium absorption in the gut, is the underlying pathophysiology for rachitic changes in hereditary vitamin D-resistant rickets (HVDRR). We describe a novel use of Cinacalcet to treat a child with HVDRR in whom conventional modes of therapy had to be discontinued. Cinacalcet therapy with high-dose oral calcium effectively normalized the metabolic abnormalities and bone condition. The relative ease of administration of the calcimimetic as a once-or twice-daily oral preparation, compared with traditional intravenous calcium administration, should encourage its move to the frontline of treatment of the disorder. ß

show abstract

Beneficial effect of cinacalcet in a child with familial hypocalciuric hypercalcemia

Cited by 52 publications

References 17 publications

Neonatal Hypercalcemia due to a Homozygous Mutation in the Calcium-Sensing Receptor: Failure of Cinacalcet

Neonatal Hypercalcemia due to a Homozygous Mutation in the Calcium-Sensing Receptor: Failure of Cinacalcet

GENETICS IN ENDOCRINOLOGY: Gain and loss of function mutations of the calcium-sensing receptor and associated proteins: current treatment concepts

Cinacalcet as adjunctive therapy for hereditary 1,25-dihydroxyvitamin D–resistant rickets

Contact Info

Product

Resources

About