Dataset Information

Novel homozygous inactivating mutation of the calcium-sensing receptor gene in neonatal severe hyperparathyroidism responding to cinacalcet therapy: A case report and literature review.

ABSTRACT: RATIONALE:Calcium-sensing receptor (CaSR) mutations can cause life-threatening neonatal severe hyperparathyroidism (NSHPT). The medical management of NSHPT is often challenging and complex. Here, we present a case of NSHPT caused by a novel homozygous CaSR mutation. PATIENT CONCERNS:A Chinese female infant presented with poor feeding, constipation, severe hypotonia, and periodic bradycardia. Biochemistry tests revealed markedly elevated serum levels of Ca and parathyroid hormone (PTH). DIAGNOSES:Genetic sequencing revealed a previously undescribed CaSR mutation in exon 3 (c.242T>A; p.I81K). A diagnosis of NSHPT secondary to homozygously inherited familial hypocalciuric hypercalcemia syndrome was established. INTERVENTIONS:Cinacalcet was administered after the common treatments (low-calcium intake, hydration, and furosemide), calcitonin, and pamidronate therapy all failed. OUTCOMES:Serum Ca decreased and stabilized with cinacalcet therapy. During a 10-month follow-up, total calcium was maintained within the high-normal range and PTH was normalized. LESSONS:A trial of cinacalcet therapy might be undertaken in cases of NSHPT while definitive results of the genetic analysis are awaited.

SUBMITTER: Sun X

PROVIDER: S-EPMC6250440 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Novel homozygous inactivating mutation of the calcium-sensing receptor gene in neonatal severe hyperparathyroidism responding to cinacalcet therapy: A case report and literature review.

Sun Xiaomei X Huang Liang L Wu Jin J Tao Yuhong Y Yang Fan F

Medicine 20181101 45

<h4>Rationale</h4>Calcium-sensing receptor (CaSR) mutations can cause life-threatening neonatal severe hyperparathyroidism (NSHPT). The medical management of NSHPT is often challenging and complex. Here, we present a case of NSHPT caused by a novel homozygous CaSR mutation.<h4>Patient concerns</h4>A Chinese female infant presented with poor feeding, constipation, severe hypotonia, and periodic bradycardia. Biochemistry tests revealed markedly elevated serum levels of Ca and parathyroid hormone ( ...[more]

PMID: 30407334

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Project description:BackgroundLoss-of-function variants in the calcium-sensing receptor (CASR) gene are known to be involved in a clinical spectrum ranging from asymptomatic familial hypocalciuric hypercalcemia (FHH) to neonatal severe hyperparathyroidism (NSHPT). Homozygous or compound heterozygous variants are usually responsible for severe neonatal forms, whereas heterozygous variants cause benign forms. One recurrent pathogenic variant, p.Arg185Gln, has been reported in both forms, in a heterozygous state. This variant can be a de novo occurrence or can be inherited from a father with FHH.NSHPT leads to global hypotonia, failure to thrive, typical X-ray anomalies (diffuse demineralization, fractures, metaphyseal irregularities), and acute respiratory distress which can be fatal. Phosphocalcic markers show severe hypercalcemia, abnormal urinary calcium resorption, and hyperparathyroidism as major signs.Classical treatment involves calcium restriction, hyperhydration, and bisphosphonates. Unfortunately, the disease often leads to parathyroidectomy. Recently, calcimimetics have been used with variable efficacy. Efficacy in NSHPT seems to be particularly dependent on CASR genotype.Case presentationWe describe the antenatal presentation of a male with short ribs, initially suspected having skeletal ciliopathy. At birth, he presented with NSHPT linked to the pathogenic heterozygous CASR variant, Arg185Gln, inherited from his father who had FHH. Postnatal therapy with cinacalcet was successful.DiscussionAn exhaustive literature review permits a comparison with all reported cases of Arg185Gln and to hypothesize that cinacalcet efficacy depends on CASR genotype. This confirms the importance of pedigree and parental history in antenatal short rib presentation and questions the feasibility of phosphocalcic exploration during pregnancy or prenatal CASR gene sequencing in the presence of specific clinical signs. It could in fact enable early calcimimetic treatment which might be effective in the CASR variant Arg185Gln.

Dataset Information

Novel homozygous inactivating mutation of the calcium-sensing receptor gene in neonatal severe hyperparathyroidism responding to cinacalcet therapy: A case report and literature review.

Publications

Novel homozygous inactivating mutation of the calcium-sensing receptor gene in neonatal severe hyperparathyroidism responding to cinacalcet therapy: A case report and literature review.

Similar Datasets

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