Clinical Spectrum of Primary Hypomagnesemia with Secondary Hypocalcemia due to TRPM6 Mutation

Hypomagnesemia type 1 (HOMG1) is a rare autosomal recessive condition due to TRPM6 gene mutation, leading to primarily impaired intestinal magnesium absorption resulting in secondary hypocalcemia. This study aimed to determine the clinical spectrum of hypomagnesemia with secondary hypocalcemia due to TRPM6 mutation.

Retrospective study carried out for a period of 2 years at the Department of Pediatric Endocrinology and Diabetes, University of Child Health Sciences, The Children's Hospital, Lahore. All genetically confirmed cases of primary hypomagnesemia due to TRPM6 mutation were clinically and biochemically reviewed to look at their clinical spectrum.

Eleven patients (n = 7 male) with homozygous TRPM6 mutation (7 novel variants) from ten different families were reported. Six cases (5 families) had a history of sibling death due to hypocalcemia seizures. Irritability and excessive crying were the first symptoms (mean age = 20 days) followed by intractable seizures (mean age = 2.07 months) in our cohort. Eight patients presented to tertiary care hospital under 6 months of age, 2 between 6 and 12 months, and 1 at 3 years of age. Initial biochemical profile in all cases revealed low magnesium, low calcium, normal/high phosphate, normal alkaline phosphatase, low/normal parathyroid hormone, normal/high 25-OH D level, and low fractional excretion of Mg. All were started on daily oral magnesium with the aim of achieving a normal biochemical profile including magnesium level. All cases are currently maintaining their bone profile on oral magnesium and are seizure free.

HOMG1 due to TRPM6 mutation is a rare condition. We are reporting 11 cases of TRPM6 mutation due to 9 different variants (7 novel). Persistent severe secondary hypocalcemia is a prominent clinical feature of TRPM6 mutation, which can be life-threatening if not treated promptly.