Genetic causes of neonatal and infantile hypercalcemia

Neonates and infants show different causes of hypercalcaemia, often distinct from those in older children and adults. Hypercalcaemia offers a wide range of symptoms, including failure to thrive, poor feeding, constipation, polyuria, irritability, lethargy, seizures, and hypotonia. 

Suspected cases of hypercalcaemia demand an evaluation of potential causes (e.g., family history) and assessment of physical features (such as dysmorphology or subcutaneous fat deposits), as well as biochemical measurements, including total and ionized serum calcium, serum phosphate, creatinine, and albumin, intact parathyroid hormone (PTH), vitamin D metabolites and urinary calcium, phosphate, and creatinine, for an accurate diagnosis. 

Neonatal hypercalcaemia can be due to high or low PTH disorders. High serum PTH Disorders include severe neonatal hyperparathyroidism, familial hypocalciuric hypercalcaemia, and Jansen's metaphyseal chondrodysplasia. Low serum PTH Conditions include idiopathic infantile hypercalcaemia, Williams-Beuren syndrome, and inborn errors of metabolism, including hypophosphatasia. Maternal hypocalcaemia, dietary factors, and several rare endocrine disorders may also influence neonatal serum calcium levels.

A recent review by Gorvin CM describes the common causes of hypercalcaemia in neonates and young infants, considering maternal, dietary, and genetic causes of calcium dysregulation. It also discusses the clinical presentation and treatment of patients with these disorders.

It additionally speculates that with the advancements in next-generation sequencing, further hypercalcemia-associated genes will be identified, which may yield new treatment avenues and continue to improve neonatal care.

Gorvin CM. Genetic causes of neonatal and infantile hypercalcaemia. Pediatr Nephrol. 2022 Feb;37(2):289-301. DOI: 10.1007/s00467-021-05082-z. Epub 2021 May 14. PMID: 33990852; PMCID: PMC8816529.