ESPE Abstracts

Background: Hypomagnesemia type 1 (HOMG1) is a rare autosomal recessive condition due to TRPM6 mutation, leading to decrease intestinal magnesium absorption.

Objective: To determine the clinical spectrum of HOMG1 due to TRPM6 mutation at a tertiary centre.

Case Series: Seven patients (all male) from six different families of hypomagnesemia type 1 due to homozygous TRPM6 mutation (parents’ carrier) were reported over last 1 years. Four different variants of TRPM6 mutation were identified and 3 of them were never reported before (novel). Most common TRPM6 variant identified was c.2538G>T p.((=)) (4/7 cases, 3 families). This variant is predicted not to change amino acid sequence, but this substitution is near the highly conserve donor splice site and is classified as likely pathogenic. There was one case with TRPM6 variant c.3514C>T p.(Arg1172*), one with c.2162C>G p.(Ser721*), and one with c.1420C>T p.(Arg474*), all creating premature stop codon. Five cases (4 families) had history of sibling deaths due to unexplained hypocalcemia fits and two cases were the first born. Irritability and excessive cry were the first symptoms (Day 9 to 1 month) followed by intractable seizures at mean age of 2.2 (1.5-3) months. Six cases presented to tertiary care between 3- 6 months, and one is delayed presentation at 3 years (taking on and off calcium and magnesium supplementation). All patients were on anticonvulsants at the time of presentation. Initial bone profile in all cases revealed low magnesium (0.4-1.1 mg/dl), low or low normal calcium (5.2-8.1 mg/dl), normal phosphate (5.2-6.8 mg/dl), normal or raised alkaline phosphatase (187-487 IU), low normal PTH (16-21.6 pg/ml), normal 25 OH D level, normal urine calcium to creatinine ratio (< 0.20) and low fractional excretion of Mg (<2% - intestinal loss). All were started on daily oral magnesium supplementation with dose of 200 mg/kg/day which was gradually increased to 336(240-400) mg/kg/day to achieve a normal magnesium level. Five cases were fit free (4 off anticonvulsants and 1 on tapering dose), however, 2 were having subtle seizures and still on anticonvulsants. Three patients were developmentally normal and 4 were having mild developmental delay.

Conclusion: Hypomagnesemia type 1 due to TRPM6 mutation is a rare condition. Early diagnosis and prompt treatment lead to favorable outcome. We are reporting 7 cases of TRPM6 mutation due to 4 different variants (3 were novel), presented with intractable seizures and responded well to oral magnesium supplementation.