Genetic causes of neonatal and infantile hypercalcaemia

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.

Hypercalcemia in Cancer: Causes, Effects, and Treatment Strategies

“…Hypercalcemia is a medical condition defined as an increase in the serum calcium level in blood above the upper limit of the reference range (>10.4 mg/dL). The causes of that medical condition are various, including overactive parathyroid glands, vitamin D disorders, or medications, but most frequently the underlying reasons are primary hyperparathyroidism and cancer, which is the most common cause of hypercalcemia in hospitalized patients [ 1 , 2 ]. Patients with cancer are commonly afflicted with hypercalcemia of malignancy (HCM) according to research, it can affect up to 44% of patients.…”

Pediatric Neuroendocrine Neoplasia of the Parathyroid Glands: Delving into Primary Hyperparathyroidism

“…This represents a dramatic condition diagnosed within the first six months after birth, usually in relation to a genetic background involving CASR. Familial hypocalciuric hypercalcemia of types 1 to 3 underline CASR anomalies that induce a mild elevation in serum calcium and PTH, starting from childhood and continuing into adulthood (which is distinct from PHP, with parathyroidectomy being unnecessary) [94][95][96]. Associated pathogenic variants involve the CASR gene on chromosome 3q 13.3-21 (loss of mutation), with more than 300 mutations described so far (60% of all familial cases), but also involving the GNA11 (guanine nucleotide-binding protein subunit alpha-11) gene, as well as the AP2S1 (adaptor protein complex 2 subunit sigma) gene, affecting 5% and 20%, respectively, of all individuals confirmed with familial hypocalciuric hypercalcemia [97][98][99].…”

Vitamin D deficiency in British South Asians, a persistent but avoidable problem associated with many health risks (including rickets, T2DM, CVD, COVID-19 and pregnancy complications): the case for correcting this deficiency

“…Many workers felt this 'outbreak' was due to unrecognized cases of Williams syndrome, and genetic causes do present this way. However, for the several admissions every week to the children's wards seen during a personal 3-month attachment to the paediatric department of an east London teaching hospital as a medical student in the late 1950s, this condition [incidence up to 20/10,000 births], [15,16] could not have been the whole explanation. This unfortunate outbreak of infantile hypercalcaemia in Britain was largely abolished by reduction of an excessive fortification of infant foodstuffs but official bodies advising on public health and nutrition have still not provided effective measures for correcting vitamin D deficiency in the UKs south Asian communities.…”