Hypomagnesaemia with secondary hypocalcaemia due to a novel TRPM6 mutation.

Hypomagnesaemia with secondary hypocalcaemia is a rare disorder characterised by severe hypomagnesaemia with moderate to severe hypocalcaemia caused by mutations in TRPM6. We report an infant born to a consanguineous marriage with multiple episodes of seizures. Investigations showed low total calcium and ionised calcium, hypomagnesaemia, normal vitamin D3 and parathyroid hormone. Fractional excretion of magnesium was 2.1%, pointing to an intestinal cause. Exome sequencing revealed a novel homozygous in-frame deletion mutation, c.1550_1552delTAG, p.(Val517del), in exon 14 of the TRPM6 gene. Sanger sequencing in the parents showed the variant to be present in heterozygous carriers. In silico analysis and protein modelling showed the variant to be deleterious to protein function. The baby was initially managed with intravenous MgSO4 and calcium gluconate correction, followed by oral high-dose magnesium sulphate and calcium supplements, and was discharged. The baby remained seizure-free on follow-up and had normal neurodevelopment appropriate for age.