Affiliation:
1. Department of Pediatrics, Apollo Multispeciality Hospitals, Kolkata, West Bengal, India
Abstract
Background:
Hypomagnesemia is an important cause of refractory hypocalcemic seizures. Among the causes of hypomagnesemia, genetic defects are rare.
Clinical Description:
A 20-month-old boy presented with a history of repeated hypocalcemic convulsions since 1 month of age. Besides seizures, the infant was thriving well and otherwise asymptomatic.
Management and Outcome:
On investigation, he had low serum calcium, normal vitamin D, low parathormone, and very low serum magnesium (0.5 mg/dl) levels, with normal sodium, potassium levels, and renal functions. The child was initiated on parenteral magnesium supplementation and subsequently discharged on high-dose oral magnesium supplementation. As further investigations ruled out common causes of hypomagnesemia, clinical exome sequencing was done, which revealed a compound heterozygous state with two variants in the TRPM6 gene NM_017662.5, one being a missense variant (chr9: c.5614T>C, [p.Trp1872Arg]/Heterozygous) and the other being a frameshift deletion (chr9: c.1939_1946delGCAATGGC, [p.Ala647Profs*2]/Heterozygous). The child maintained normal serum magnesium levels at follow-up and was seizure-free.
Conclusion:
Hereditary hypomagnesemia with secondary hypocalcemia is a rare cause of refractory seizures with onset since early infancy. Here, a compound heterozygous variant of the TRPM6 gene was identified as the cause of this condition.