Hypercalcemia in children: an overview

Area of Science:

• Pediatric Endocrinology
• Genetics
• Calcium Metabolism

Background:

• Hypercalcemia in children, especially serum calcium over 15 mg/dL, presents a significant health risk.
• Familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NHPT) are distinct conditions affecting calcium homeostasis.
• Recent discoveries include the isolation of a complementary DNA for an extracellular calcium-sensing receptor.

Purpose of the Study:

• To explore the association between FHH and NHPT.
• To investigate the role of calcium-sensing receptor gene mutations in these conditions.
• To discuss other causes of pediatric hypercalcemia, including vitamin D-related issues.

Main Methods:

• Characterization of FHH by high serum calcium, low urine calcium, and normal parathyroid hormone (PTH).
• Description of NHPT as a severe, often fatal, hypercalcemic condition requiring early intervention.
• Identification of three mutations in the calcium-sensing receptor gene in individuals with FHH and NHPT.

Main Results:

• Heterozygotes for FHH mutations may exhibit intermittent hypercalcemia.
• Homozygotes for FHH mutations may present with NHPT.
• The calcium-sensing receptor gene mutations provide a genetic link between FHH and NHPT.

Conclusions:

• Mutations in the calcium-sensing receptor gene are implicated in both FHH and NHPT.
• Genetic analysis offers insights into the pathogenesis of severe pediatric hypercalcemia.
• Understanding these genetic links is crucial for diagnosis and management of calcium disorders in children.