ProgramsView all programs
From the news
- Chancellor Amma Addresses the Parliament of World’s Religions
- Amrita Students Qualify for the European Mars Rover Challenge
Publication Type : Journal Article
Thematic Areas : Medical Sciences
Publisher : J Clin Endocrinol Metab
Source : J Clin Endocrinol Metab, Volume 101, Issue 11, p.4283-4289 (2016)
Keywords : Child, Preschool, female, Humans, hypercalcemia, infant, male, Osteochondrodysplasias, parathyroid hormone, Pedigree, Receptor, Parathyroid Hormone, Type 1
Campus : Kochi
School : School of Medicine
Department : Paediatrics
Year : 2016
Abstract : CONTEXT: /bJansen's metaphyseal chondrodysplasia (JMC) is a rare skeletal dysplasia characterized by abnormal endochondral bone formation and typically severe hypercalcemia despite normal/low levels of PTH. Five different heterozygous activating PTH/PTHrP receptor (PTH1R) mutations that change one of three different amino acid residues are known to cause JMC.bOBJECTIVES: /bEstablishing the diagnosis of JMC during infancy or early childhood can be challenging, especially in the absence of family history and/or overt hypercalcemia. We therefore sought to provide radiographic findings supporting this diagnosis early in life./ppbPATIENTS AND METHODS: /bThree patients, a mother and her two sons, had radiographic evidence for JMC. However, obvious hypercalcemia and suppressed PTH levels were encountered only in both affected children. Sanger sequencing and endonuclease (SphI) digestion of PCR-amplified genomic DNA were performed to search for the H223R-PTH1R mutation./ppbRESULTS: /bThe heterozygous H223R mutation was identified in all three affected individuals. Surprisingly, however, the now 38-year-old mother was never overtly hypercalcemic and was therefore not diagnosed until her sons were found to be affected by JMC at the ages of 28 months and 40 days, respectively. The presented radiographic findings at different ages will help diagnose other infants/toddlers suspected of having JMC.CONCLUSION:The H223R mutation is typically associated with profound hypercalcemia despite low/normal PTH levels. However, the findings presented herein show that overt hypercalcemia is not always encountered in JMC, even if caused by this relatively frequent mutation, which is similar to observations with other PTH1R mutations that show less constitutive activity.
Cite this Research Publication : S. Nampoothiri, Fernández-Rebollo, E., Yesodharan, D., Gardella, T. J., Rush, E. T., Langman, C. B., and Jüppner, H., “Jansen Metaphyseal Chondrodysplasia due to Heterozygous H223R-PTH1R Mutations With or Without Overt Hypercalcemia.”, J Clin Endocrinol Metab, vol. 101, no. 11, pp. 4283-4289, 2016.