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European Journal of Pediatrics

, Volume 163, Issue 10, pp 589–594 | Cite as

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

  • Simon Waller
  • Tom Kurzawinski
  • Lewis Spitz
  • Rajesh Thakker
  • Treena Cranston
  • Simon Pearce
  • Tim Cheetham
  • William G. van’t HoffEmail author
Original Paper

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 

Abbreviations

CaSR

calcium sensing receptor

FHH

familial hypocalciuric hypercalcaemia

NSHPT

neonatal severe hyperparathyroidism

PTx

parathyroidectomy

Notes

Acknowledgements

S Waller is partly funded by the special trustees of Great Ormond Street Hospital. We thank Dr Gerald McEnery for referring two of the patients for further management.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Simon Waller
    • 1
  • Tom Kurzawinski
    • 2
  • Lewis Spitz
    • 3
  • Rajesh Thakker
    • 4
  • Treena Cranston
    • 5
  • Simon Pearce
    • 6
  • Tim Cheetham
    • 6
  • William G. van’t Hoff
    • 1
    Email author
  1. 1.Nephro-Urology UnitInstitute of Child Health, University College of London Medical Schools and Great Ormond Street Hospital for Children NHS TrustLondon UK
  2. 2.Pancreatic and Endocrine Surgical UnitThe Middlesex Hospital, University College London Hospitals NHS TrustLondon UK
  3. 3.Department of SurgeryGreat Ormond Street Hospital for Children NHS TrustLondonUK
  4. 4.Nuffield Department of Clinical MedicineUniversity of OxfordOxford UK
  5. 5.Genetics LaboratoriesOxford Radcliffe Hospitals NHS TrustOxford UK
  6. 6.Royal Victoria InfirmaryThe Newcastle Upon Tyne Hospitals NHS TrustNewcastle Upon Tyne UK

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