Hereditary hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disease due to biallelic TRPM6 mutations. Although the reports of HSH caused by TRPM6 mutations are not very rare, the age of onset in previously reported HSH cases were <1 year.
We collected and analyzed the clinical data of twin brothers with onset age over 1 year old and performed whole exome sequencing in the patients and their parents. Confirmed by Sanger sequencing, missense mutation was analyzed
The twin patients had canonical HSH phenotype with compound novel TRPM6 mutations, p.T87K and c.705dupT, inherited from their father and mother, respectively. T87 is a highly conserved site and T87K is predicted to cause hydrogen bond disruption. We identified 26 articles published between May 28, 2002 to December 31, 2021 which reported a total of 88 patients with TRPM6 mutation. We found that the most common clinical phenotypes were hypomagnesemia, hypocalcemia, and convulsions. However, the age of onset in HSH patients almost always occurred under 12 months old, the twin patients of our study were 18 and 26 months old at onset.
We identified two novel TRPM6 mutations in a Chinses family with HSH, and showed that the age of onset with c.704c-c.705(exon7)insT and c.260(exon4)C>A mutation in TRPM6 was much later than other mutations and would be much less serious.