Vitamin B6–Responsive Epilepsy due to a Novel KCNQ2 Mutation

Kerstin Alexandra Klotz; Johannes R. Lemke; Rudolf Korinthenberg; Julia Jacobs

doi:10.1055/s-0037-1601857

Neuropediatrics, Table of Contents

Neuropediatrics 2017; 48(03): 199-204
DOI: 10.1055/s-0037-1601857

Short Communication

Georg Thieme Verlag KG Stuttgart, New York

Vitamin B₆–Responsive Epilepsy due to a Novel KCNQ2 Mutation

Authors

Kerstin Alexandra Klotz

¹Department of Neuropediatrics and Muscle Disorders, Center for Pediatrics, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Johannes R. Lemke

²Institute of Human Genetics, University Hospitals, University of Leipzig, Leipzig, Germany
Rudolf Korinthenberg

¹Department of Neuropediatrics and Muscle Disorders, Center for Pediatrics, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Julia Jacobs

¹Department of Neuropediatrics and Muscle Disorders, Center for Pediatrics, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Abstract

Mutations in KCNQ2, encoding for subunits of potassium channels, are known to cause neonatal epileptic encephalopathy (NEE). Therapeutic options for these children are often limited. Recently, there are indications that some patients with KCNQ2 NEE show seizure response to vitamin B₆ (VB₆) therapy. We present a young infant with severe KCNQ2 encephalopathy resulting from a novel de novo mutation (c.1023G>C; p.(Gln341His)). In our patient, VB₆ responsiveness could be demonstrated clearly by remarkable seizure-response to VB₆ therapy and seizure exacerbation to discontinuation of VB₆ therapy. The pathophysiology of VB₆ response in potassium channel mutations is not understood. Some hypothetical mechanisms are currently in discussion. To identify the group of patients who benefits from VB₆ therapy, further investigations are necessary.

Keywords

KCNQ2 - vitamin B₆ - pyridoxine-responsive-epilepsy - neonatal epileptic encephalopathy

Full Text

References

References
1 Biervert C, Schroeder BC, Kubisch C , et al. A potassium channel mutation in neonatal human epilepsy. Science 1998; 279 (5349): 403-406
2 Singh NA, Charlier C, Stauffer D , et al. A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nat Genet 1998; 18 (1) 25-29
3 Borgatti R, Zucca C, Cavallini A , et al. A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation. Neurology 2004; 63 (1) 57-65
4 Steinlein OK, Conrad C, Weidner B. Benign familial neonatal convulsions: always benign?. Epilepsy Res 2007; 73 (3) 245-249
5 Weckhuysen S, Mandelstam S, Suls A , et al. KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol 2012; 71 (1) 15-25
6 Kato M, Yamagata T, Kubota M , et al. Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia 2013; 54 (7) 1282-1287
7 Milh M, Boutry-Kryza N, Sutera-Sardo J , et al. Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2. Orphanet J Rare Dis 2013; 8: 80
8 Weckhuysen S, Ivanovic V, Hendrickx R , et al; KCNQ2 Study Group. Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients. Neurology 2013; 81 (19) 1697-1703
9 Pisano T, Numis AL, Heavin SB , et al. Early and effective treatment of KCNQ2 encephalopathy. Epilepsia 2015; 56 (5) 685-691
10 Barrese V, Miceli F, Soldovieri MV , et al. Neuronal potassium channel openers in the management of epilepsy: role and potential of retigabine. Clin Pharmacol 2010; 2: 225-236
11 Millichap JJ, Park KL, Tsuchida T , et al. KCNQ2 encephalopathy: features, mutational hot spots, and ezogabine treatment of 11 patients. Neurol Genet 2016; 2 (5) e96
12 Plecko B. Pyridoxine and pyridoxal phosphate-dependent epilepsies. Handb Clin Neurol 2013; 113: 1811-1817
13 Mills PB, Camuzeaux SSM, Footitt EJ , et al. Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome. Brain 2014; 137 (Pt 5): 1350-1360
14 Plecko B, Hikel C, Korenke G-C , et al. Pipecolic acid as a diagnostic marker of pyridoxine-dependent epilepsy. Neuropediatrics 2005; 36 (3) 200-205
15 Hansson O, Hagberg B. Effect of pyridoxine treatment in children with epilepsy. Acta Soc Med Ups 1968; 73 (1) 35-43
16 Ohtahara S. A study on the age-dependent epileptic encephalopathy. [in Japanese]. No To Hattatsu 1977; (9) 2-21
17 Ohtahara S, Yamatogi Y, Ohtsuka Y. Vitamin B(6) treatment of intractable seizures. Brain Dev 2011; 33 (9) 783-789
18 Mefford HC, Cook J, Gospe Jr SM. Epilepsy due to 20q13.33 subtelomere deletion masquerading as pyridoxine-dependent epilepsy. Am J Med Genet A 2012; 158A (12) 3190-3195
19 Reid ES, Williams H, Stabej PleQ , et al. Seizures due to a KCNQ2 mutation: treatment with vitamin B6. JIMD Rep 2016; 27: 79-84
20 Allen NM, Mannion M, Conroy J , et al. The variable phenotypes of KCNQ-related epilepsy. Epilepsia 2014; 55 (9) e99-e105
21 Richards S, Aziz N, Bale S , et al; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17 (5) 405-424
22 Plecko B, Paul K, Mills P , et al. Pyridoxine responsiveness in novel mutations of the PNPO gene. Neurology 2014; 82 (16) 1425-1433
23 Footitt EJ, Heales SJ, Mills PB, Allen GFG, Oppenheim M, Clayton PT. Pyridoxal 5′-phosphate in cerebrospinal fluid; factors affecting concentration. J Inherit Metab Dis 2011; 34 (2) 529-538
24 Chumnantana R, Yokochi N, Yagi T. Vitamin B6 compounds prevent the death of yeast cells due to menadione, a reactive oxygen generator. Biochim Biophys Acta 2005; 1722 (1) 84-91
25 Kannan K, Jain SK. Effect of vitamin B6 on oxygen radicals, mitochondrial membrane potential, and lipid peroxidation in H2O2-treated U937 monocytes. Free Radic Biol Med 2004; 36 (4) 423-428
26 Thériault O, Poulin H, Thomas GR, Friesen AD, Al-Shaqha WA, Chahine M. Pyridoxal-5′-phosphate (MC-1), a vitamin B6 derivative, inhibits expressed P2X receptors. Can J Physiol Pharmacol 2014; 92 (3) 189-196
27 Henshall DC, Diaz-Hernandez M, Miras-Portugal MT, Engel T. P2X receptors as targets for the treatment of status epilepticus. Front Cell Neurosci 2013; 7: 237
28 Jimenez-Pacheco A, Mesuret G, Sanz-Rodriguez A , et al. Increased neocortical expression of the P2X7 receptor after status epilepticus and anticonvulsant effect of P2X7 receptor antagonist A-438079. Epilepsia 2013; 54 (9) 1551-1561
29 Wang H-S, Kuo M-F, Chou M-L , et al. Pyridoxal phosphate is better than pyridoxine for controlling idiopathic intractable epilepsy. Arch Dis Child 2005; 90 (5) 512-515
30 Gospe Jr SM. Neonatal vitamin-responsive epileptic encephalopathies. Chang Gung Med J 2010; 33 (1) 1-12
31 Stockler S, Plecko B, Gospe Jr SM , et al. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab 2011; 104 (1-2): 48-60
32 Schenker S, Johnson RF, Mahuren JD, Henderson GI, Coburn SP. Human placental vitamin B6 (pyridoxal) transport: normal characteristics and effects of ethanol. Am J Physiol 1992; 262 (6 Pt 2): R966-R974
33 Iqbal MP, Lindblad BS, Mehboobali N, Yusuf FA, Khan AH, Iqbal SP. Folic acid and vitamin B6 deficiencies related hyperhomocysteinemia in apparently healthy Pakistani adults: is mass micronutrient supplementation indicated in this population?. J Coll Physicians Surg Pak 2009; 19 (5) 308-312
34 Devaux J, Abidi A, Roubertie A , et al. A Kv7.2 mutation associated with early onset epileptic encephalopathy with suppression-burst enhances Kv7/M channel activity. Epilepsia 2016; 57 (5) e87-e93
35 Sudarsanam A, Singh H, Wilcken B , et al. Cirrhosis associated with pyridoxal 5′-phosphate treatment of pyridoxamine 5′-phosphate oxidase deficiency. JIMD Rep 2014; 17: 67-70
36 Takuma Y, Seki T. Combination therapy of infantile spasms with high-dose pyridoxal phosphate and low-dose corticotropin. J Child Neurol 1996; 11 (1) 35-40
37 Yoshida I, Sakaguchi Y, Nakano M, Yamashita F, Hitoshi T. Pyridoxal phosphate-induced liver injury in a patient with homocystinuria. J Inherit Metab Dis 1985; 8 (2) 91