ArticleThe Journal of clinical endocrinology and metabolism2020
Neonatal Severe Hyperparathyroidism: Novel Insights From Calcium, PTH, and the CASR Gene.
Article in The Journal of clinical endocrinology and metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Long-term follow-up of neonatal severe hyperparathyroidism: redefining calcium management.Archives of endocrinology and metabolism · 2026Article
- Endocrine Disorders of Calcium Signaling in Children: Neuroendocrine Crosstalk and Clinical Implications.Cells · 2026Review
- Hyperinsulinemic hypoglycemia due to pathogenic INSR variants: metabolic signature, phenotypic overlap, and semidominant inheritance.Frontiers in endocrinology · 2026Article
- Management of Neonatal Severe Hyperparathyroidism due to HomozygousMolecular syndromology · 2025Article
- Heritable hyperparathyroidism: Genetic insights and clinical implications.Best practice & research. Clinical endocrinology & metabolism · 2025Review
- Precision stratified treatment of primary hyperparathyroidism based on multilevel emerging biomarkers.Frontiers in endocrinology · 2025Review
- Familial states of primary hyperparathyroidism: an update.Journal of endocrinological investigation · 2024Review
- Neonatal Severe Hyperparathyroidism Causing Life-Threatening Hypercalcemia Treated With Medical and Surgical Management.JCEM case reports · 2024Article
- Demineralization of Osseous Structures as Presentation of a Rare Genetic Disorder That Is Associated With a High Rate of Mortality.Case reports in endocrinology · 2024Article
- Wolf-Hirschhorn Syndrome with Hyperparathyroidism: A Case Report and a Narrative Review of the Literature.Journal of pediatric genetics · 2023Article
- Molecular and Clinical Spectrum of Primary Hyperparathyroidism.Endocrine reviews · 2023Article
- Ten-year follow-up report and neurologic sequelae in a case of neonatal severe primary hyperparathyroidism.Clinical case reports · 2023Article
- Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Review
- Genetics of monogenic disorders of calcium and bone metabolism.Clinical endocrinology · 2022Review
- Disorders of the Calcium Sensing Signaling Pathway: From Familial Hypocalciuric Hypercalcemia (FHH) to Life Threatening Conditions in Infancy.Journal of clinical medicine · 2022Review
- Genetic causes of neonatal and infantile hypercalcaemia.Pediatric nephrology (Berlin, Germany) · 2022Review
- Article
- Review
- Integrated bioinformatic analysis identifies COL4A3, COL4A4, and KCNJ1 as key biomarkers in Wilms tumor.International journal of clinical and experimental pathology · 2021Article
- Case Report: Severe Neonatal Course in Paternally Derived Familial Hypocalciuric Hypercalcemia.Frontiers in endocrinology · 2021Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
contextNeonatal severe hyperparathyroidism (NSHPT) is rare and potentially lethal. It is usually from homozygous or heterozygous germline-inactivating CASR variant(s). NSHPT shows a puzzling range of serum calcium and parathyroid hormone (PTH) levels. Optimal therapy is unclear. EVIDENCE ACQUISITION: We categorized genotype/phenotype pairings related to CASRs. For the 2 pairings in NSHPT, each of 57 cases of neonatal severe hyperparathyroidism required calcium, PTH, upper normal PTH, and dosage of a germline pathogenic CASR variant. EVIDENCE SYNTHESIS: Homozygous and heterozygous NSHPT are 2 among a spectrum of 9 genotype/phenotype pairings relating to CASRs and NSHPT. For the 2 NSHPT pairings, expressions differ in CASR allelic dosage, CASR variant severity, and sufficiency of maternofetal calcium fluxes. Homozygous dosage of CASR variants was generally more aggressive than heterozygous. Among heterozygotes, high-grade CASR variants in vitro were more pathogenic in vivo than low-grade variants. Fetal calcium insufficiency as from maternal hypoparathyroidism caused fetal secondary hyperparathyroidism, which persisted and was reversible in neonates. Among NSHPT pairings, calcium and PTH were higher in CASR homozygotes than in heterozygotes. Extreme hypercalcemia (above 4.5 mM; normal 2.2-2.6 mM) is a robust biomarker, occurring only in homozygotes (83% of that pairing). It could occur during the first week.
conclusionsIn NSHPT pairings, the homozygotes for pathogenic CASR variants show higher calcium and PTH levels than heterozygotes. Calcium levels above 4.5 mM among NSHPT are frequent and unique only to most homozygotes. This cutoff supports early and robust diagnosis of CASR dosage. Thereby, it promotes definitive total parathyroidectomy in most homozygotes.
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