Rickets and metabolic bone disease — formative SAQs

SAQ 1 (10 marks) — The hypocalcaemic seizing infant

Stem: A six-month-old, exclusively breastfed infant of a veiled migrant mother presents in late winter with a brief generalised seizure. The child is afebrile and looks well between events. The ionised calcium is 0.85 mmol per litre, the phosphate is 1.2 mmol per litre, the alkaline phosphatase is 920 units per litre, and the parathyroid hormone is raised. Outline your immediate and definitive management, and explain the principle that governs the order of the drugs. [3] [1]

Model answer

Resuscitation — intravenous calcium first (3 marks). This is symptomatic hypocalcaemia from nutritional vitamin D deficiency rickets, an emergency. Give intravenous calcium gluconate slowly through a secure large-bore line with continuous cardiac monitoring, because rapid infusion can cause bradycardia and arrest. Terminate the seizure with calcium rather than standard anticonvulsants, which are ineffective for hypocalcaemic seizures. Check and correct magnesium and avoid alkalosis, which lowers ionised calcium. [3] [1]

The principle — calcium before vitamin D (2 marks). Give oral calcium before or with the cholecalciferol, never vitamin D alone. High-dose vitamin D accelerates bone mineralisation and can deepen the hypocalcaemia through hungry bone, the rapid uptake of calcium and phosphate by the healing skeleton; giving a stoss vitamin D dose without concurrent calcium is the classic avoidable error that can trigger further seizures and, rarely, cardiac compromise. [1] [4]

Definitive treatment (3 marks). Once the calcium is stable, start cholecalciferol 2000 IU daily for three months, or a stoss dose of 100 000 to 300 000 IU, together with oral calcium at 30 to 50 mg per kilogram per day elemental. The choice of daily versus stoss depends on adherence; the stoss regimen suits a family for whom a daily dose is uncertain. Send a 25-hydroxyvitamin D to confirm the deficiency and a wrist radiograph to stage the rickets. [1] [4]

Monitoring and public health (2 marks). Check the alkaline phosphatase and calcium at four to six weeks — the alkaline phosphatase should be falling — and repeat the radiograph at three months to document healing, which is expected by three to six months. Screen and supplement the mother and any siblings, because nutritional rickets in one infant signals household risk. Counsel the family that exclusive breastfeeding was the right choice and that the supplement is safe, and arrange primary-care follow-up to sustain 400 IU daily through adolescence. [2] [5]

SAQ 2 (10 marks) — A normal vitamin D level with rickets

Stem: A two-year-old boy presents with progressive leg bowing, short stature, and two dental abscesses. The calcium is normal, the phosphate is 0.6 mmol per litre, the alkaline phosphatase is raised, the parathyroid hormone is normal, and the 25-hydroxyvitamin D is 75 nmol per litre. Discuss the diagnosis, the further investigations, and the principles of treatment, and explain why vitamin D alone will not heal this child. [5] [1]

Model answer

Diagnosis (3 marks). This is phosphopenic rickets, and the most likely cause is X-linked hypophosphataemia. The signature is a markedly low phosphate with a normal calcium, a normal parathyroid hormone, and a normal 25-hydroxyvitamin D. The dental abscesses and the disproportionate, leg-predominant short stature are characteristic. The 1,25-dihydroxyvitamin D is inappropriately low because FGF23 suppresses the renal 1-alpha-hydroxylase. This is FGF23-mediated renal phosphate wasting, classically from a PHEX mutation, and it is X-linked dominant. [5]

Why vitamin D alone fails (2 marks). The growth plate is starved of phosphate, not of calcium, and the parathyroid axis is intact and not driving the disease. Loading with cholecalciferol raises the 25-hydroxyvitamin D but cannot restore the phosphate, because FGF23 continues to waste it, and it cannot raise the suppressed 1,25-dihydroxyvitamin D. Treatment must bypass the FGF23-suppressed 1-alpha-hydroxylase with active calcitriol and replace the wasted phosphate directly. [5] [4]

Further investigations (2 marks). Confirm renal phosphate wasting with a fasting phosphate and a calculated tubular maximum for phosphate reabsorption relative to glomerular filtration (TmP per GFR), which is low. Send an FGF23 level, which is inappropriately raised, and arrange genetic testing for a PHEX mutation. A wrist and knee radiograph stages the rickets, and a renal ultrasound is the baseline for monitoring the nephrocalcinosis that complicates phosphate therapy. Assess hearing and arrange a dental review, because the dentin defect drives the abscesses. [5]

Treatment and monitoring (3 marks). Conventional therapy is oral phosphate in four to six divided daily doses together with calcitriol, which bypasses the suppressed 1-alpha-hydroxylase; the phosphate is divided because of its poor absorption and osmotic effect. Burosumab, a monoclonal antibody against FGF23, is now licensed from age one year and offers an alternative that normalises phosphate without the nephrocalcinosis and secondary hyperparathyroidism of conventional phosphate. Monitor calcium, phosphate, alkaline phosphatase, parathyroid hormone, renal ultrasound for nephrocalcinosis, growth, and the rickets radiograph, and manage the limb deformity with the orthopaedic team once the metabolic disease is biochemically controlled. The child needs lifelong multidisciplinary care with a planned transition to adult endocrinology. [4] [5]