ESPE Abstracts (2016) 86 WG4.2

Oxford, UK

Hypercalcaemic disorders in children may present with poor feeding, hypotonia, lethargy, dehydration, vomiting, polyuria, failure to thrive, seizures and hypertension. The causes of hypercalcaemia in children, which can be classified as parathyroid hormone (PTH)-dependent or PTH-independent, are similar to those occurring in adults except that primary hyperparathyroidism and malignancy which the most common causes in adults, and account for >90% of adult patients with hypercalcaemia, are rare in children. Moreover, genetic causes of hypercalcaemia, which may be syndromic or non-syndromic, are common in children. Thus, genetic causes of hypercalcaemia in children include those associated with: elevated serum PTH, e.g., neonatal severe primary hyperparathyroidism (due to calcium-sensing receptor (CaSR) mutations), and the multiple endocrine neoplasia (MEN) types 1, 2/3, and 4 (MEN1-4) syndromes (due to mutations of the tumour suppressor gene, MEN1, that encodes menin, RET proto oncogene encoding a receptor tyrosine kinase, and cyclin-dependent kinase inhibitor 1B (CDKN1B), respectively); inappropriate serum PTH concentrations due to altered sensitivity of the CaSR and its signalling pathway e.g., familial hypocalciuric hypercalcaemia (FHH) types 1, 2 and 3 (FHH1-3) (due to mutations of CaSR, G-protein alpha 11 subunit, and adaptor protein 2 sigma subunit, respectively); and low serum PTH concentrations e.g., infantile hypercalcaemic (due to mutations of the vitamin D 24-hydroxylase (CYP24A1) gene), William’s syndrome (due to a micro-deletion of chromosome 7q11.23), Jansen’s disease (due to activating mutations of the PTH receptor), and hypophosphatasia (due to mutations of tissue-non specific alkaline phosphate). Non-genetic (acquired) causes of hypercalcaemia in children include: vitamin D intoxication, vitamin A intoxication, subacute fat necrosis, granulomatous diseases (e.g., tuberculosis, sarcoidosis, cat-scratch fever), and inflammatory disorders (e.g., Crohn’s disease). Advances in identifying the genetic causes that have resulted in increased understanding of the underlying biological pathways and improvements in diagnosis and treatments will be discussed.

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