A novel TRPM6 variant (c.3179T>A) causing familial hypomagnesemia with secondary hypocalcemia

Abstract

Summary

Familial hypomagnesemia with secondary hypocalcemia (FHSH) is a rare autosomal recessive disorder (OMIM# 602014) characterized by profound hypomagnesemia associated with hypocalcemia. It is caused by mutations in the gene encoding transient receptor potential cation channel member 6 (TRPM6). It usually presents with neurological symptoms in the first months of life. We report a case of a neonate presenting with recurrent seizures and severe hypomagnesemia. The genetic testing revealed a novel variant in the TRPM6 gene. The patient has been treated with high-dose magnesium supplementation, remaining asymptomatic and without neurological sequelae until adulthood. Early diagnosis and treatment are important to prevent irreversible neurological damage.

Learning points:

• Loss-of-function mutations of TRPM6 are associated with FHSH.

• FHSH should be considered in any child with refractory hypocalcemic seizures, especially in cases with serum magnesium levels as low as 0.2 mM.

• Normocalcemia and relief of clinical symptoms can be assured by administration of high doses of magnesium.

• Untreated, the disorder may be fatal or may result in irreversible neurological damage.