Neonatal severe hyperparathyroidism: further clinical and molecular delineation.
We report a newborn female from a consanguineous Sri Lankan family with clinical and biochemical features of neonatal severe hyperparathyroidism (NSHPT). Mutation screening of the calcium-sensing receptor (CASR) gene in genomic DNA revealed a homozygous truncating mutation (c.679C>T, predicting p.R227X), confirming the clinical diagnosis. Other mutations at the R227 position are reported to cause varying degrees of hypercalcemia and hyperparathyroidism, but this nonsense variant is novel and expected to induce unremitting hyperparathyroidism from birth onward. In our patient with NSHPT, early bisphosphonate therapy was crucial in counteracting the marked hypercalcemia and allowed for safe surgical intervention ("total" parathyroidectomy, "thymectomy and hemithyroidectomy") at 3 months of age.


CONCLUSIONS
This report highlights the continuing challenges in diagnosis and management of this life-threatening condition.
Section of Pediatric Endocrinology, Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.
Fawziya A
FA
Al-Khalaf
Adel
A
Ismail
Ashraf T
AT
Soliman
David E C
DE
Cole
Tawfeg
T
Ben-Omran
D018389:Codon, Nonsense; D005260:Female; D006720:Homozygote; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D007231:Infant, Newborn; D009154:Mutation; D044169:Receptors, Calcium-Sensing / Q000235:genetics*
C095550:CASR protein, human; D018389:Codon, Nonsense; D044169:Receptors, Calcium-Sensing