Calcium, magnesium and phosphate disorders — formative SAQs

SAQ 1 (10)

A 10-day-old exclusively formula-fed neonate presents with a generalised seizure. Total calcium is 1.6 mmol/L with an albumin of 35 g/L, phosphate is 3.6 mmol/L, and the ionised calcium is 0.85 mmol/L. The neonate is jittery but maintains the airway. [1][3]

1. Correct the calcium for albumin and define hypocalcaemia, and explain why the phosphate is high. (3) [1]
2. Give the emergency management, naming the drug, dose, route, rate and monitoring, and state the key peripheral-safety point. (4) [1][3]
3. If the calcium fails to rise after two adequate doses, name the single most likely cause and its treatment, and explain the mechanism. (3) [7]

Model answer

Correction and definition. The correction adds 0.02 mmol/L for each gram per litre that albumin is below 40 g/L. The albumin is 35, so the deficit is 5 g/L and the correction is 0.1 mmol/L; the corrected calcium is 1.7 mmol/L. Hypocalcaemia is a corrected calcium below 2.1 mmol/L or an ionised below about 1.1 mmol/L, and an ionised of 0.85 is severe. The phosphate is high because this is late neonatal hypocalcaemia driven by a phosphate load from cow-milk formula; the high phosphate complexes calcium and depresses the ionised fraction. [1]

Emergency management. Give intravenous 10 percent calcium gluconate at 0.5 to 1 mL per kilogram, to a maximum of about 20 mL, slowly over 5 to 10 minutes with continuous cardiac monitoring. Calcium gluconate rather than calcium chloride is preferred peripherally because it is less vesicant if it extravasates, and a good intravenous line is essential because extravasation causes tissue necrosis. Stop the infusion if the heart rate drops, because rapid calcium itself causes bradycardia and arrhythmia. [1][3]

Refractory cause. If the calcium fails to rise, the single most likely cause is hypomagnesaemia. Low magnesium suppresses parathyroid hormone release, producing a functional hypoparathyroidism that no amount of calcium will correct, and it disinhibits the ROMK channel to cause concurrent renal potassium loss. The treatment is magnesium sulfate 25 to 50 mg per kilogram, to a maximum of 2 g, intravenously over 2 to 4 hours with monitoring. [7]

SAQ 2 (10)

A 4-year-old boy has short stature, progressive leg bowing, and dental abscesses. His calcium is 2.3 mmol/L (normal), phosphate 0.7 mmol/L (low), parathyroid hormone normal, alkaline phosphatase markedly raised, and fibroblast growth factor 23 elevated. [9][5]

1. Give the diagnosis and explain the pathophysiology of the low phosphate, contrasting it with vitamin D deficiency rickets. (4) [9]
2. Outline the current guideline-recommended treatment and how it differs from conventional therapy. (3) [9]
3. Describe the surveillance plan and two complications of conventional therapy that the modern treatment avoids. (3) [9][5]

Model answer

Diagnosis and pathophysiology. This is X-linked hypophosphataemic rickets, caused by a PHEX mutation that drives excess fibroblast growth factor 23. The excess FGF23 forces the kidney to waste phosphate and switches off calcitriol, so the phosphate falls while the calcium and parathyroid hormone remain normal. This is the key contrast with vitamin D deficiency rickets, where the low calcitriol lowers calcium, which drives secondary hyperparathyroidism, which then lowers phosphate; both raise the alkaline phosphatase, so the calcium and parathyroid hormone are the discriminators. [9]

Treatment. The current international guideline-recommended standard is burosumab, a monoclonal antibody that binds and neutralises fibroblast growth factor 23, restoring phosphate reabsorption and calcitriol, healing the rickets, and improving linear growth and bowing. This differs from conventional therapy with oral phosphate in divided doses plus calcitriol, which is harder to titrate and carries a risk of secondary hyperparathyroidism and nephrocalcinosis. [9]

Surveillance and complications. Surveillance monitors phosphate, calcium, parathyroid hormone, alkaline phosphatase, renal function, growth, and renal ultrasound for nephrocalcinosis, with regular assessment of bowing and need for orthopaedic input. Two complications of conventional therapy that burosumab avoids are secondary hyperparathyroidism from intermittent phosphate dosing and nephrocalcinosis from chronic phosphate and calcium loading. [9][5]