Abstract
The causes of hypercalcaemia in the neonate and infant are varied, and often distinct from those in older children and adults. Hypercalcaemia presents clinically with a range of symptoms including failure to thrive, poor feeding, constipation, polyuria, irritability, lethargy, seizures and hypotonia. When hypercalcaemia is suspected, an accurate diagnosis will require an evaluation of potential causes (e.g. family history) and assessment for physical features (such as dysmorphology, or subcutaneous fat deposits), as well as biochemical measurements, including total and ionised serum calcium, serum phosphate, creatinine and albumin, intact parathyroid hormone (PTH), vitamin D metabolites and urinary calcium, phosphate and creatinine. The causes of neonatal hypercalcaemia can be classified into high or low PTH disorders. Disorders associated with high serum PTH include neonatal severe hyperparathyroidism, familial hypocalciuric hypercalcaemia and Jansen’s metaphyseal chondrodysplasia. Conditions associated with low serum PTH include idiopathic infantile hypercalcaemia, Williams-Beuren syndrome and inborn errors of metabolism, including hypophosphatasia. Maternal hypocalcaemia and dietary factors and several rare endocrine disorders can also influence neonatal serum calcium levels. This review will focus on the common causes of hypercalcaemia in neonates and young infants, considering maternal, dietary, and genetic causes of calcium dysregulation. The clinical presentation and treatment of patients with these disorders will be discussed.
Highlights
Hypercalcaemia in the neonate and infant, uncommon, can have serious long-term consequences, including nephrocalcinosis that may cause permanent kidney damage, osteoporosis and neurodevelopmental impairments, and has varied etiologies (Table 1)
When serum calcium concentrations are low, the parathyroid glands synthesise and secrete parathyroid hormone (PTH), which acts on PTH receptors (PTH1R) on bone and kidney cells
At the kidney proximal tubule, FGF binding to the FGF receptor (FGFR)–klotho complex stimulates signalling pathways that decrease PTH transcription and reduce plasma membrane expression of sodium–phosphate transporters resulting in reduced phosphate uptake and increased urinary excretion
Summary
Hypercalcaemia in the neonate and infant, uncommon, can have serious long-term consequences, including nephrocalcinosis that may cause permanent kidney damage, osteoporosis and neurodevelopmental impairments, and has varied etiologies (Table 1). Hypercalcaemia is defined as a serum calcium concentration two standard deviations greater than the normal mean. An accurate determination of the serum calcium concentration with age-appropriate normal ranges (Table 2) is required as serum calcium levels are higher in newborns and preterm infants and decline with age [1, 3].
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