Neonatal severe hyperparathyroidism: genotype/phenotype correlation and the use of pamidronate as rescue therapy

Authors: Waller, Simon¹; Kurzawinski, Tom²; Spitz, Lewis³; Thakker, Rajesh⁴; Cranston, Treena⁵; Pearce, Simon⁶; Cheetham, Tim⁶; Hoff, William⁷

Source: European Journal of Pediatrics, Volume 163, Number 10, October 2004 , pp. 589-594(6)

Publisher: Springer

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Abstract:

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant condition due to heterozygous loss of function calcium sensing receptor (CaSR) mutations. However, individuals who are homozygous for CaSR mutations have neonatal severe hyperparathyroidism (NSHPT), which unlike the relatively benign and asymptomatic FHH can be fatal without parathyroidectomy. We report three patients with NSHPT associated with marked hypercalcaemia and severe hyperparathyroidism with related skeletal demineralisation. We describe the novel use of intravenous pamidronate in NSHPT, to control severe hypercalcaemia in these patients prior to parathyroidectomy and in one individual as a rescue therapy to stabilise life-threatening demineralisation. Furthermore, a marked phenotypic heterogeneity was observed amongst four members from a large kindred with the same homozygous CaSR mutations: one patient would have died without parathyroidectomy in infancy; a second patient survived infancy but underwent parathyroidectomy in early childhood following severe symptomatic hypercalcaemic episodes; whilst the other two patients have survived to adolescence without parathyroidectomy. Additionally, in contrast to the literature these two individuals suffered minimal morbidity. Conclusion:we commend the short-term use of pamidronate in neonatal severe hyperparathyroidism to treat extreme hypercalcaemia and halt hyperparathyroid-driven skeletal demineralisation in preparation for parathyroidectomy. The remarkable degree of phenotypic variation demonstrated remains unexplained without functional studies; this variability highlights the challenge of treating this rare condition.

Keywords: Calcium sensing receptor; Familial hypocalciuric hypercalcaemia; Parathyroidectomy

Document Type: Research article

DOI: 10.1007/s00431-004-1491-0

Affiliations: 1: Nephro-Urology Unit, Institute of Child Health, University College of London Medical Schools and Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, WC1N 3JH, London , UK, 2: Pancreatic and Endocrine Surgical Unit, The Middlesex Hospital, University College London Hospitals NHS Trust, London, UK, 3: Department of Surgery, Great Ormond Street Hospital for Children NHS Trust, London, UK , 4: Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK , 5: Genetics Laboratories, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK, 6: Royal Victoria Infirmary, The Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, UK, 7: Nephro-Urology Unit, Institute of Child Health, University College of London Medical Schools and Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, WC1N 3JH, London , UK, Email: vanthw@gosh.nhs.uk

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