title: Neonatal severe hyperparathyroidism caused by homozygous mutation in CASR: A rare cause of life-threatening hypercalcemia.
abstract: Neonatal severe hyperparathyroidism (NSHPT) is a rare, life-threatening condition that presents with severe hypercalcemia, hyperparathyroidism, and osteopenia in the newborn period. Treatment of NSHPT traditionally includes hydration and bisphosphonates; however newer calcimimetic agents, such as cinacalcet, are now being utilized to prevent or delay parathyroidectomy which is technically difficult in the newborn. Medical treatment success is related to calcium sensing receptor (CaSR) genotype. We report a 4-day-old infant who presented with hyperbilirubinemia, poor feeding, weight loss, severe hypotonia and was ultimately diagnosed with NSHPT. The patient's total serum calcium level of 36.8 mg/dL (reference range: 8.5-10.4 mg/dL) is, to our knowledge, the highest ever documented in this setting. Exome data previously obtained on the infant's parents was re-analyzed demonstrating bi-parental heterozygosity for a mutation of the CASR gene: c.206G > A, and Sanger sequencing data confirmed the patient was a homozygote for the same mutation. Though a patient with the same CaSR gene mutation described here has responded to cinacalcet, our patient did not respond and required parathyroidectomy. Though this case has previously been published as a surgical case report, a full report of the medical management and underlying genetic etiology is warranted; this case underscores the importance of disclosing bi-parental heterozygosity for a gene causing severe neonatal disease particularly when treatment is available and illustrates the need for further in vitro studies of this CaSR mutation.
authors: Department of Pediatrics, Louisiana State University Health Science Center, USA.
authors: Heidi
authors: H
authors: Murphy
authors: Division of Neonatology, Department of Pediatrics, Louisiana State University Health Science Center, USA.
authors: Jessica
authors: J
authors: Patrick
authors: Division of Endocrinology, Department of Pediatrics, Louisiana State University Health Science Center, USA.
authors: Eileen
authors: E
authors: Báez-Irizarry
authors: Division of Genetics, Department of Pediatrics, Louisiana State University Health Science Center, USA; Department of Genetics, Children's Hospital of New Orleans, USA.
authors: Yves
authors: Y
authors: Lacassie
authors: Division of Endocrinology, Department of Pediatrics, Louisiana State University Health Science Center, USA; Department of Endocrinology, Children's Hospital of New Orleans, USA.
authors: Ricardo
authors: R
authors: Gómez
authors: Division of Endocrinology, Department of Pediatrics, Louisiana State University Health Science Center, USA; Department of Endocrinology, Children's Hospital of New Orleans, USA.
authors: Alfonso
authors: A
authors: Vargas
authors: Division of Neonatology, Department of Pediatrics, Louisiana State University Health Science Center, USA; Department of Neonatology, Children's Hospital of New Orleans, USA.
authors: Brian
authors: B
authors: Barkemeyer
authors: Division of Otorlaryngology, Department of Pediatrics, Louisiana State University Health Science Center, USA; Department of Otolaryngology Children's Hospital of New Orleans, USA.
authors: Sohit
authors: S
authors: Kanotra
authors: Division of Genetics, Department of Pediatrics, Louisiana State University Health Science Center, USA; Department of Genetics, Children's Hospital of New Orleans, USA. Electronic address: rzambr@lsuhsc.edu.
authors: Regina M
authors: RM
authors: Zambrano
mesh_terms: D005838:Genotype; D006801:Humans; D006932:Hyperbilirubinemia / Q000235:genetics* / Q000473:pathology; D006934:Hypercalcemia / Q000235:genetics* / Q000503:physiopathology; D006961:Hyperparathyroidism / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery; D007231:Infant, Newborn; D009154:Mutation; D016105:Parathyroidectomy; D044169:Receptors, Calcium-Sensing / Q000235:genetics*
chemical_list: C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing
keywords: CASR; Calcimimetic; Exome data; Neonatal severe hyperparathyroidism