Intestinal hypomagnesemia-two cases of recurrent seizures: a diagnostic odyssey
DOI:
https://doi.org/10.18203/2349-3291.ijcp20241692Keywords:
Hypomagnesemia, Seizures, InfancyAbstract
Familial hypomagnesemia with secondary hypocalcemia (FHSH) is a rare autosomal recessive disorder that is manifested as severe hypomagnesemia and moderate to severe hypocalcemia. Affected children present with refractory seizures in infancy. It results from mutations in the gene encoding transient receptor potential cation channel member 6 (TRPM6) on chromosome 9q22. The primary defect is impaired intestinal absorption of magnesium with secondary defect in the renal conservation of magnesium. We report two infants who presented with refractory seizures beginning in the first three months of life, the clinical phenotype of both these children was normal. Both were diagnosed to have hypocalcemic seizures. The children were managed with intravenous calcium and magnesium during their hospital stay, however were discharged on calcium supplementation alone. As they continued to have seizures inspite of good compliance to medications and in view of persistently low magnesium levels, hypomagnesemia as a cause of seizures was considered. Genetic evaluation revealed variants in the TRPM6 gene in both the cases The seizures were brought under control once the magnesium levels were normalized. A possibility of hypomagnesemia with secondary hypocalcemia should be thought of in any case of refractory hypocalcemia and inappropriately low levels of parathyroid hormone (PTH) The purpose of this series is to highlight the importance of systematically working up children with inherited hypomagnesemia.
References
Xi Q, Hoenderop JG, Bindels RJ. Regulation of magnesium reabsorption in DCT. Pflugers Arch. 2009;458(1):89-98.
de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiol Rev. 2015;95(1):1-46.
Eisner RF, Turnbull TL, Howes DS, Gold IW. Efficacy of a "standard" seizure workup in the emergency department. Ann Emerg Med. 1986;15(1):33-9.
Weisleder P, Tobin JA, Kerrigan JF 3rd, Bodensteiner JB. Hypomagnesemic seizures: case report and presumed pathophysiology. J Child Neurol. 2002;17(1):59-61.
Konrad M, Schlingmann KP. Inherited disorders of renal hypomagnesaemia. Nephrol Dial Transplant. 2014;29(4):iv63-71.
Elisaf M, Panteli K, Theodorou J, Siamopoulos KC. Fractional excretion of magnesium in normal subjects and in patients with hypomagnesemia. Magnes Res. 1997;10(4):315-20.
Ahmed F, Mohammed A. Magnesium: The Forgotten Electrolyte-A Review on Hypomagnesemia. Med Sci (Basel). 2019;7(4):56.
Kamate M, Singh N, Patil S. Familial Hypomagnesemia with Secondary Hypocalcemia Mimicking Neurodegenerative Disorder. Indian Pediatr. 2015;52(6):521-2.
Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington (DC): National Academies Press (US). 1997.
Agus ZS. Hypomagnesemia. J Am Soc Nephrol. 1999;10(7):1616-22.
Gröber U. Magnesium and Drugs. Int J Mol Sci. 2019;20(9):2094.
Walder RY, Landau D, Meyer P, Shalev H, Tsolia M, Borochowitz Z, et al. Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nat Genet. 2002;31(2):171-4.
Schlingmann KP, Sassen MC, Weber S, Pechmann U, Kusch K, Pelken L, et al. Novel TRPM6 mutations in 21 families with primary hypomagnesemia and secondary hypocalcemia. J Am Soc Nephrol. 2005;16(10):3061-9.
Viering DHHM, de Baaij JHF, Walsh SB, Kleta R, Bockenhauer D. Genetic causes of hypomagnesemia, a clinical overview. Pediatr Nephrol. 2017;32(7):1123-35.
Schlingmann KP, Weber S, Peters M. Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat Genet. 2002;31(2):166-70.
Joshi R, Phatarpekar A. Hypomagnesaemia with secondary hypocalcaemia due to TRPM6 gene mutation. Sri Lanka J Child Health. 2012;41:205-6.
Kekatpure MV, Gaur S, Dash GK, Kannan S. TRPM6 mutation: A novel cause of “reversible” infantile epileptic encephalopathy. Neurol India. 2016;64:1037-8.
Lal N, Bhardwaj S, Lalgudi Ganesan S, Sharma R, Jain P. Case of hypomagnesemia with secondary hypocalcemia with a novel TRPM6 mutation. Neurol India. 2018;66:1795-800.
Geethalakshmi S, Bhavani N, Vinayan KP, Nair V. Rare Inherited Hypomagnesemias – An Endocrine Case Series. Indian Pediatr. 2021;58(5):489-90.
