Neonatal severe hyperparathyroidism caused by homozygous mutation in CASR: A rare cause of life-threatening hypercalcemia

Murphy, Heidi J; Patrick, Jessica; Báez-Irizarry, Eileen; Lacassie, Yves; Gómez, Ricardo; Vargas, Alfonso; Barkemeyer, Brian; Kanotra, Sohit Paul; Zambrano, Regina

doi:10.1016/j.ejmg.2016.02.001

Cited by 27 publications

(29 citation statements)

References 12 publications

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“…We had one neonate who presented with a severe course of hypercalcemia consistent with previous reports of NSHPT and repeated hypercalcemia occurring shortly after surgery, suggesting an ectopic fifth parathyroid gland ( 29 , 30 ).…”

Section: Discussionsupporting

confidence: 85%

Childhood Sustained Hypercalcemia: A Diagnostic Challenge

İlarslan

Şıklar

Berberoğlu

2017

Jcrpe

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Objective:This study aimed to call attention to hypercalcemia, a rare finding in children which carries the potential of leading to serious complications without proper intervention.Methods:Diagnosis, treatment, and clinical course of children with sustained hypercalcemia admitted between the years 2006-2016 were reviewed. Group 1 [parathyroid hormone (PTH)-dependent] consisted of patients with high/unsuppressed PTH levels and group 2 (PTH-independent) included cases with normal/suppressed PTH levels.Results:Twenty patients (11 male, 9 female) with a median age of 6.25 (0.03-17.88) years were evaluated. Symptoms were mostly related with the gastrointestinal system, while six patients (30%) were asymptomatic. Physical examination findings were diverse, non-specific, and normal in four patients (20%). Median time of diagnosis was 45 (2-720) days. Patients were divided into group 1 (n=7) and group 2 (n=13). Most frequent etiologies were primary hyperparathyroidism (n=5), idiopathic infantile hypercalcemia (IIH) (n=5), and malignancy (n=4). A moderate positive correlation was noted between serum calcium and creatinine levels (r=0.53, p=0.02). Nephrocalcinosis was the most common complication (n=9) (45%). Treatment was not implemented in 2 patients with mild hypercalcemia, while other patients received medical treatment ± surgery. Treatment-resistant patients were cases of malignancies and neonatal severe hyperparathyroidism. Long-term follow-up displayed resistant hypercalciuria in three infants diagnosed as IIH.Conclusion:Many patients with childhood hypercalcemia are asymptomatic or exhibit a non-specific and heterogeneous clinical presentation, resulting in delayed diagnosis. Mild cases may not be recognized, while symptoms may be missed in the presence of accompanying illnesses. Nevertheless, serious complications may only be avoided with prompt diagnosis and intervention.

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Section: Discussionsupporting

confidence: 85%

Childhood Sustained Hypercalcemia: A Diagnostic Challenge

İlarslan

Şıklar

Berberoğlu

2017

Jcrpe

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“…This is consistent with Soblechero et al that reported a case of neonatal hypercalcemia due to a homozygous deletion/frameshift mutation in the CaSR in which there was therapeutic failure of Cinacalcet [ 1 ]. The success or failure in response to therapy with Cinacalcet can depend on the CASR genotype [ 24 ]. In all cases of NSHPT, a trial with Cinacalcet could be attempted but, if ineffective, definitive surgical treatment is necessary.…”

Section: Discussionmentioning

confidence: 99%

Case report: acute clinical presentation and neonatal management of primary hyperparathyroidism due to a novel CaSR mutation

et al. 2018

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BackgroundNeonatal severe primary hyperparathyroidism (NSHPT) is a rare autosomal recessive disorder of calcium homeostasis, characterized by striking hyperparathyroidism, marked hypercalcemia and hyperparathyroid bone disease. We report the case of a newborn with a novel homozygous mutation of the CaSR, treated by successful subtotal parathyroidectomy, who had an acute presentation of the disease, i.e. out-of hospital cardiorespiratory arrest. .Case presentationA 8-day-old female newborn was admitted to the NICU of University of Bari “Aldo Moro” (Italy) after a cardiorespiratory arrest occurred at home. Severe hypercalcemia was found and different drug therapies were employed (Furosemide, Cinacalcet and bisphosphonate), as well as hyperhydration, until subtotal parathyroidectomy, was performed at day 32. Our patient’s mutation was never described before so that a strict and individualized long-term follow-up was started.ConclusionsThis case of NSHPT suggests that a near-miss event, labelled as a possible case of SIDS, could also be due to severe hypercalcemia and evidentiates the difficulties of the neonatal management of NSHPT. Furthermore, the identification of the specific CaSR mutation provides the substrate for prenatal diagnosis.

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“…In some cases, pamidronate was found to control severe hypercalcemia, enabling the postponement or avoidance of surgery. [ 6 , 8 , 10 , 18 ] However, there have been reports of Ca 2+ levels decreasing temporarily following bisphosphonate administration but then subsequently increasing, [ 1 , 12 , 19 , 20 ] while other cases have shown no apparent immediate fall in serum Ca 2+ . [ 7 , 8 ] Hypercalcemia in NSHPT has a multifactorial etiology and is not simply secondary to rampant bone resorption [ 6 , 19 ] ; pamidronate has limited efficacy and does not specifically address the problem of abnormal CaSR function.…”

Section: Discussionmentioning

confidence: 99%

Novel homozygous inactivating mutation of the calcium-sensing receptor gene in neonatal severe hyperparathyroidism responding to cinacalcet therapy

Sun¹,

Huang

Wu³

et al. 2018

Medicine

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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 Ca2+ 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 Ca2+ 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.

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Neonatal severe hyperparathyroidism caused by homozygous mutation in CASR: A rare cause of life-threatening hypercalcemia

Cited by 27 publications

References 12 publications

Childhood Sustained Hypercalcemia: A Diagnostic Challenge

Childhood Sustained Hypercalcemia: A Diagnostic Challenge

Case report: acute clinical presentation and neonatal management of primary hyperparathyroidism due to a novel CaSR mutation

Novel homozygous inactivating mutation of the calcium-sensing receptor gene in neonatal severe hyperparathyroidism responding to cinacalcet therapy

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