Anticonvulsant treatment associated with intractable hypocalcaemia in a female child with hypoparathyroidism

We report the case of a female infant with hypoparathyroidism due to an activating mutation in the calcium-sensing receptor gene.

The child presented in the neonatal period with clinical seizures associated with severe hypocalcaemia, hyperphosphataemia, low parathyroid hormone levels and elevated urine calcium:creatinine ratios. She required intravenous calcium and phenobarbitone initially, and then oral 1-alfacalcidol (1-AC) and phenobarbitone were started. The patient had intractable hypocalcaemia in the first 5 months of life despite escalating doses of 1-AC. When the phenobarbitone was stopped at 5 months of age she was admitted soon after with symptomatic hypercalcaemia. We postulate that the phenobarbitone increased the metabolism of 1-AC and thus she needed large doses of 1-AC to treat hypocalcaemia until the phenobarbitone was stopped. Her parents had no biochemical abnormalities on testing.

Molecular genetic analysis confirmed that our patient had a de novo missense variant, c.682G>A (p.Glu228Lys) in exon 4 of the calcium-sensing receptor.

This case report highlights the importance that clinicians caring for children on vitamin D and its analogues are aware of the interaction with phenobarbitone, which can result in symptomatic hypocalcaemia. 1-AC should be stored at 2-8°C, otherwise it will be rendered inactive.