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Table of Contents    
LETTER TO EDITOR
Year : 2016  |  Volume : 64  |  Issue : 5  |  Page : 1037-1038

TRPM6 mutation: A novel cause of “reversible” infantile epileptic encephalopathy


1 Department of Neurology, Division of Pediatric Neurology, Narayana Health, Mazumdar Shaw Medical Center, Bengaluru, Karnataka, India
2 Department of Pediatrics, Division of Pediatric Neurology, Narayana Health, Mazumdar Shaw Medical Center, Bengaluru, Karnataka, India
3 Department of Neurology, Division of Epileptology, Narayana Health, Mazumdar Shaw Medical Center, Bengaluru, Karnataka, India
4 Department of Endocrinology, Narayana Health, Mazumdar Shaw Medical Center, Bengaluru, Karnataka, India

Date of Web Publication12-Sep-2016

Correspondence Address:
Minal Vikram Kekatpure
Department of Neurology, Division of Pediatric Neurology, Narayana Health, Mazumdar Shaw Medical Center, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.190253

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How to cite this article:
Kekatpure MV, Gaur S, Dash GK, Kannan S. TRPM6 mutation: A novel cause of “reversible” infantile epileptic encephalopathy. Neurol India 2016;64:1037-8

How to cite this URL:
Kekatpure MV, Gaur S, Dash GK, Kannan S. TRPM6 mutation: A novel cause of “reversible” infantile epileptic encephalopathy. Neurol India [serial online] 2016 [cited 2021 Sep 28];64:1037-8. Available from: https://www.neurologyindia.com/text.asp?2016/64/5/1037/190253




Sir,

Hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disorder, first described by Paunier et al., caused by mutation in the gene on chromosome 9q22, the TRPM6 gene.[1],[2] HSH is characterized by an early infantile onset of neurological symptoms, with subsequent irreversible neurological damage and eventual death, due to a failure to institute an early treatment.[3]

We report a case of HSH with an unusual presentation of myoclonic epilepsy and developmental regression with a complete reversal of symptoms following magnesium supplementation.

A 7-month-old female child, born of nonconsanguineous parents, was evaluated for recurrent multifocal clonic and myoclonic seizures associated with developmental regression since 2 months. Perinatal and family histories were noncontributory. Neurological examination was notable for moderate developmental delay, normal head circumference and fundi, frequent myoclonus (>60 clusters/day) despite four anticonvulsant drugs (ACDs), absent neurocutaneous markers or organomegaly. Chvostek and Trousseau's sign were negative. Laboratory reports revealed hypocalcemia (6 mg/dl, range 8.5–10.2 mg/dl), persisting despite emergent intravenous calcium correction; euglycemia, severe hypomagnesemia (0.1 mg/dl, range 1.7–2.3 mg/dl), normal parathyroid hormone, and vitamin D levels; unremarkable skeletal radiographs with negative evaluation for renal tubular acidosis and Barter syndrome.

Prolonged video electroencephalogram (EEG) recorded several myoclonic and clonic seizures with no EEG correlates or interictal epileptiform abnormalities. Magnetic resonance imaging of the brain was unremarkable with normal basal ganglia. An extensive systemic and cerebrospinal fluid evaluation for sepsis or a metabolic disorder was noncontributory. Whole exome sequencing ruled out a sodium channelopathy and revealed homozygous mutation in exon 19 of TRPM6 gene ([Chr9: 77407598; C > T; c. 2480G>A] resulting in stop codon and premature truncation of protein at codon 827 [p. W827Ter] was detected). Further, both parents were found to be heterozygous carriers of the same mutation. A diagnosis of TRMP6 related HSH was established. Magnesium supplementation at 0.5 g/kg/day was initiated and continued. At a 1-year follow-up, the child was seizure free, off ACD, with normocalcemia and serum magnesium levels between 1.4 and 1.7 mg/dl. Her neurodevelopment was currently age appropriate.

To the best of our knowledge, myoclonic epilepsy due to HSH has not been reported. This patient had no basal ganglia calcification as reported in a few other children with HSH.[4]

Impaired voltage-dependent magnesium gating of N-methyl-D aspartate receptor is epileptogenic, and may cause hypomagnesemic seizures.[5] TRPM6 knockout mice developed neural tube defects and had abnormal central nervous system development,[6] suggesting that TRPM6 may have as yet unknown functions directly involving neuronal development and functioning.

Diagnosing HSH can be a clinical challenge. It is noteworthy that simple biochemical parameters of hypomagnesemia and hypocalcemia were useful pointers towards the eventual diagnosis. Early diagnosis of HSH is essential to avoid unnecessary ACD therapy, prevent irreversible neurological damage and eventual death.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Paunier L, Radde IC, Kooh SW, Conen PE, Fraser D. Primary hypomagnesemia with secondary hypocalcemia in an infant. Pediatrics 1968;41:385-402.  Back to cited text no. 1
[PUBMED]    
2.
Walder RY, Shalev H, Brennan TM, Carmi R, Elbedour K, Scott DA, et al. Familial hypomagnesemia maps to chromosome 9q, not to the X chromosome: Genetic linkage mapping and analysis of a balanced translocation breakpoint. Hum Mol Genet 1997;6:1491-7.  Back to cited text no. 2
[PUBMED]    
3.
Katayama K, Povalko N, Yatsuga S, Nishioka J, Kakuma T, Matsuishi T, et al. New TRPM6 mutation and management of hypomagnesaemia with secondary hypocalcaemia. Brain Dev 2015;37:292-8.  Back to cited text no. 3
[PUBMED]    
4.
Habeb AM, Al-Harbi H, Schlingmann KP. Resolving basal ganglia calcification in hereditary hypomagnesemia with secondary hypocalcemia due to a novel TRPM6 gene mutation. Saudi J Kidney Dis Transpl 2012;23:1038-42.  Back to cited text no. 4
[PUBMED]  Medknow Journal  
5.
Hartnett KA, Stout AK, Rajdev S, Rosenberg PA, Reynolds IJ, Aizenman E. NMDA receptor-mediated neurotoxicity: A paradoxical requirement for extracellular Mg2+in Na+/Ca2+-free solutions in rat cortical neurons in vitro. J Neurochem 1997;68:1836-45.  Back to cited text no. 5
    
6.
Walder RY, Yang B, Stokes JB, Kirby PA, Cao X, Shi P, et al. Mice defective in TRPM6 show embryonic mortality and neural tube defects. Hum Mol Genet 2009;18:4367-75.  Back to cited text no. 6
[PUBMED]    




 

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