Hypocalcaemia and hypoparathyroidism

The organising principle is the calcium–PTH axis: the parathyroid calcium-sensing receptor detects a fall in ionised calcium, the chief cells release parathyroid hormone, and PTH restores calcium by mobilising bone, reabsorbing calcium in the kidney, and — indirectly through activated vitamin D — increasing gut absorption. Hypoparathyroidism breaks this axis at the source: no PTH is made. Pseudohypoparathyroidism breaks it at the target organ: PTH is made in abundance but the kidney and bone cannot respond. Vitamin D deficiency breaks it at the gut. Knowing where the axis breaks is the fastest route to the right diagnosis and treatment. ^{[3] [8]}

This page covers the full breadth of paediatric hypocalcaemia: the physiology of calcium homeostasis, the PTH-led classification, neonatal early- and late-onset hypocalcaemia, 22q11.2 deletion (DiGeorge) syndrome, autoimmune polyglandular syndrome type 1, pseudohypoparathyroidism, acute symptomatic management with intravenous calcium, and the long-term trio of oral calcium, calcitriol and PTH 1-34. It cross-links to the rickets and metabolic bone disease leaf rather than repeating the full vitamin D pathway. ^{[1] [7]}

Overview & Definition

Hypocalcaemia is a serum total calcium below 2.1 millimoles per litre, or an ionised calcium below 1.1 millimoles per litre. Total calcium must be corrected for albumin: add 0.02 millimoles per litre for every gram per litre that albumin is below 40. The ionised calcium is the physiologically active fraction, and it is the better test in acutely ill children, neonates, and any child with acid–base disturbance, because albumin and protein binding shift with pH. ^{[3] [8]}

Hypoparathyroidism is the state in which parathyroid hormone is deficient (or, in pseudohypoparathyroidism, resisted), so calcium falls and phosphate rises. The clinical syndrome is neuromuscular irritability: paraesthesiae around the mouth and in the fingers, muscle cramping, carpopedal spasm, and in severe cases laryngospasm, bronchospasm, and generalised seizures. Infants and young children often present with a seizure as the first sign, with no preceding history of tingling. ^{[1] [3]}

References10ShowHide

1. [1]Brandi ML; Bilezikian JP; Shoback D; et al Management of Hypoparathyroidism: Summary Statement and Guidelines. J Clin Endocrinol Metab, 2016.PMID 26943719
2. [2]Khan AA; Koch CA; Van Uum SHM; et al Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines from the Second International Workshop. J Bone Miner Res, 2022.PMID 36054621
3. [3]Mannstadt M; Bilezikian JP; Thakker RV; et al Hypoparathyroidism. Nat Rev Dis Primers, 2017.PMID 28857066
4. [4]Mantovani G; Bastepe M; Monk D; et al Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement. Nat Rev Endocrinol, 2018.PMID 29959430
5. [5]Winer KK; Kelly A; Johns A; et al Long-Term Parathyroid Hormone 1-34 Replacement Therapy in Children with Hypoparathyroidism. J Pediatr, 2018.PMID 30470382
6. [6]Winer KK; Sinaii N; Peterson D; et al Effects of once versus twice-daily parathyroid hormone 1-34 therapy in children with hypoparathyroidism. J Clin Endocrinol Metab, 2008.PMID 18492754
7. [7]Khan AA; Clarke BL; Rejnmark L; et al Best practice recommendations for the diagnosis and management of hypoparathyroidism. Metabolism, 2025.PMID 40581321
8. [8]Hsu SC; Levine MA Perinatal calcium metabolism: physiology and pathophysiology. Semin Neonatol, 2004.PMID 15013473
9. [9]Wahrmann S; Jokinen E; Pitkänen S; et al Childhood manifestations of 22q11.2 deletion syndrome: A Finnish nationwide register-based cohort study. Acta Paediatr, 2023.PMID 36867048
10. [10]Munns CF; Shaw N; Kiely M; et al Global Consensus Recommendations on Prevention and Management of Nutritional Rickets. J Clin Endocrinol Metab, 2016.PMID 26745253