Neonatal Severe Primary Hyperparathyroidism (NSHPT)

Neonatal Severe Primary Hyperparathyroidism (NSHPT) is a rare, life-threatening disorder characterized by very high serum calcium concentrations, skeletal demineralization, and multi-glandular parathyroid hyperplasia. Infants present with lethargy, hypotonia, failure to thrive, bony undermineralization, multiple fractures, and severe skeletal deformities, including thoracic narrowing that can lead to respiratory disease. Symptoms occur before the age of 6 months and, if left untreated, can lead to florid rickets, devastating neurodevelopmental disorders, and often fatality. Usually a parathyroidectomy is necessary within the first few weeks of life to prevent death. Of note, there have been milder, transient cases reported with a lack of family history of FHH or secondary hyperparathyroidism. NSHPT is inherited in an autosomal recessive manner, and affected infants are usually born to parents with FHH who may be consanguineous. Milder, transient neonatal disease may be seen when one or both of the parents are symptomatic. In rare cases, a single heterozygous mutation has been reported to act in a dominant-negative fashion. Paternal and de novo mutations tend to have a less severe clinical course due to the influence of maternal-fetal calcium regulations.

Tests Available

Forms and Documents

Test Details

CASR
  • Distinguish FHH from primary hyperparathyroidism and other disorders of calcium homeostasis
  • Confirmation of a clinical diagnosis
  • To determine appropriate treatment, including avoidance of parathyroidectomy in FHH patients
  • Prenatal diagnosis in pregnancies at-risk for NSHPT
  • Capillary Sequencing

Ordering

170
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81405x1
No
Yes
  • 275.4 Disorders of calcium metabolism
* For price inquiries please email zebras@genedx.com

References

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  2. Chou et al., (1995) Am J Hum Genet 56:1075-1079
  3. Pearce et al., (1995) J Clin Invest 96:2683-2692
  4. Pearce et al., (1996) NEJM 335(15):1115-1122
  5. Hendy et al., (2000) Hum Mut 16:281-296
  6. Hendy et al.,(2003) J of Clin Endocrin & Metab 88(8):3674-3681
  7. Warner et al., (2004) J Med Genet 41(3):155-60
  8. Lienhardt et al (2001) J Clin Endocr Metab 86:5313-5323
  9. Thakker (2004) Cell Calcium 35:275-28
  10. Gunn et al (2004) Ann Clin Biochem 41:441-58
  11. Simonds et al., (2002) Medicine (Baltimore) 81:1-26