Bone Abstracts

Background: A 3 month-old boy was born at term, to non-consanguineous parents by spontaneous vaginal delivery, in good condition, weighing 4.19 kg. Newborn examination, including eyes, was normal prior to discharge. He has two older brothers in good health.

Presenting problem: He was admitted at 7 days of life with focal seizures and hypocalcaemia (1.5 mmol/l), hypomagnesaemia (0.6 mmol/l), hyperphosphataemia (3.7 mmol/l) and inappropriately low parathyroid hormone levels (<0.3 pmol/l). He was treated with intravenous calcium and magnesium infusions and discharged home on oral calcium, magnesium and alfacalcidol. He was re-admitted at five weeks with recurrent focal seizures and hypocalcaemia that persisted despite intravenous calcium infusions. Parents noticed he had stopped fixing and following over the previous week. Eye examination revealed nystagmus and absent red reflexes. He was urgently reviewed by Ophthalmology who confirmed presence of dense bilateral cataract.

Clinical management: An activating variant in the calcium sensing receptor (CaSR) gene was suspected and confirmed by genetic analysis. He was commenced on a subcutaneous parathyroid hormone infusion and weaned off intravenous calcium infusion. Alfacalcidol was stopped and colecalciferol was started. Thiazide diuretics were commenced to reduce renal calcium excretion. CSF analysis and MRI brain were normal. Ultrasound abdomen showed mild nephrocalcinosis. Urine calcium creatinine ratio was regularly monitored. Seizures settled after resolution of hypocalcaemia. He was operated for cataract at nine weeks of life.

Discussion: The CaSR is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. Activating CASR gene variants result in an increased calcium sensitivity in parathyroid and renal cells, which in turn reduces the parathyroid set point and reduces renal calcium reabsorption despite prevailing hypocalcaemia. The clinical presentation varies from mild paraesthesia and muscle cramps to nephrocalcinosis, nephrolithiasis, basal ganglia calcifications and seizures, while some remain asymptomatic.

Cataracts are a recognised complication of hypoparathyroidism. However, as far as we are aware, this is the first reported case of cataract in an infant with activating CASR mutation, although it has been previously identified in mouse models. We therefore suggest that evaluation for cataract is required in this subgroup of patients.

Disclosure: The authors declared no competing interests.