Alternating Hemiplegia of Childhood Caused by <italic style="font-style: italic">ATP1A3</italic> Mutations: A Report of Two Cases

Yang Guange; Zhao Zhongli; Yang Yang; Lin Li; Song Conglei; Wang Xiaocui; Yang Bin

doi:10.24920/003850

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Alternating Hemiplegia of Childhood Caused by ATP1A3 Mutations: A Report of Two Cases

Chinese Medical Sciences Journal Vol. 36, Issue 2, Pages: 150-157(2021)

Case Reports | Updated：2024-04-10

- Alternating Hemiplegia of Childhood Caused by ATP1A3 Mutations: A Report of Two Cases
- Affiliations：
  
  Medical Department of Neurology, Anhui Provincial Children’s Hospital, Hefei 230053, China
- Author bio：
  
  *Tel: 86-551-62237720, E-mail: guangeyang@163.com
- Funds：
- DOI：10.24920/003850
  CLC：
- Received：10 February 2021，
  
  Published Online：31 May 2021，
  
  Published：30 June 2021
- Accepted：
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Yang Guange, Zhao Zhongli, Yang Yang, et al. Alternating Hemiplegia of Childhood Caused by ATP1A3 Mutations: A Report of Two Cases[J]. Chinese medical sciences journal, 2021, 36(2): 150-157.
DOI：

Yang Guange, Zhao Zhongli, Yang Yang, et al. Alternating Hemiplegia of Childhood Caused by ATP1A3 Mutations: A Report of Two Cases[J]. Chinese medical sciences journal, 2021, 36(2): 150-157. DOI： 10.24920/003850.

摘要

儿童交替性偏瘫是一种罕见的神经发育性异常

绝大多数为散发病例

极少数有家族史。我院收治2例男性患儿

6~7月龄时开始癫痫发作

表现为反复发作性全身无力或一侧肢体偏瘫。基因检测显示两患儿均携带

ATP1A3

基因杂合缺失突变（OMIM:614820）：c.3025（exon 22）A

G（p.K1009E）和c.2443（exon 18）G

A（p.E815K）。氟桂利嗪可以显著改善交替性偏瘫患儿的发作性运动症状。

Abstract

Alternating hemiplegia of childhood is a rare neurodevelopmental disorder. Most cases are reported as sporadic disorder due to

de novo

variants

and few with family members involved. Two boys were hospitalized due to epileptic seizures occurred initially at age of six to seven months. During the course of the disease

there were repeated episodes of paroxysmal weakness or paralysis affecting one side of the body. Genetic testing showed that both patients carried heterozygous missense mutations in the

ATP1A3

gene (OMIM: 614820): c.3025 (exon 22) A

G (p.K1009E) and c.2443 (exon 18) G

A (p.E815K). Flunarizine can significantly improve the paroxysmal motor symptoms of pediatric patients with alternating hemiplegia.

关键词

Keywords

references

Verret S , Steele JC . Alternating hemiplegia in childhood: a report of eight patients with complicated migraine beginning in infancy . Pediatrics 1971 ; 47 ( 4 ): 675 - 80 .

Neville BGR , Ninan M . The treatment and management of alternating hemiplegia of childhood . Dev Med Child Neurol 2007 ; 49 ( 10 ): 777 - 80 . doi: 10.1111/j.1469-8749.2007.00777.x 1001-9294-36-2-150/j.1469-8749.2007.00777.x . DOI: 10.1111/j.1469-8749.2007.00777.x http://doi.org/10.1111/j.1469-8749.2007.00777.x http://blackwell-synergy.com/doi/abs/10.1111/dmcn.2007.49.issue-10 http://blackwell-synergy.com/doi/abs/10.1111/dmcn.2007.49.issue-10

Bourgeois M , Aicardi J , Goutieres F . Alternating hemiplegia of childhood . J Pediatr 1993 ; 122 ( 5 Pt 1 ): 673 - 9 . doi: 10.1016/s0022-3476(06)80003-x 1001-9294-36-2-150/s0022-3476(06)80003-x . DOI: 10.1016/s0022-3476(06)80003-x http://doi.org/10.1016/s0022-3476(06)80003-x https://linkinghub.elsevier.com/retrieve/pii/S002234760680003X https://linkinghub.elsevier.com/retrieve/pii/S002234760680003X

Heinzen EL , Swoboda KJ , Hitomi Y , et al . De novo mutations in ATP1A3 cause alternating hemiplegia of childhood . Nat Genet 2012 ; 44 ( 9 ): 1030 - 4 . doi: 10.1038/ng.2358 1001-9294-36-2-150/ng.2358 . DOI: 10.1038/ng.2358 http://doi.org/10.1038/ng.2358 https://doi.org/10.1038/ng.2358 https://doi.org/10.1038/ng.2358

Rosewich H , Thiele H , Ohlenbusch A , et al . Heterozygous denovo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study . Lancet Neurol 2012 ; 11 ( 9 ): 764 - 73 . doi: 10.1016/S1474-4422(12)70182-5 1001-9294-36-2-150/S1474-4422(12)70182-5 . DOI: 10.1016/S1474-4422(12)70182-5 http://doi.org/10.1016/S1474-4422(12)70182-5

Capuano A , Garone G , Tiralongo G , et al . Alternating hemiplegia of childhood: understanding the genotypephenotype relationship of ATP1A3 variations . Appl Clin Genet 2020 ; 13 : 71 - 81 . doi: 10.2147/TACG.S210325 1001-9294-36-2-150/TACG.S210325 . DOI: 10.2147/TACG.S210325 http://doi.org/10.2147/TACG.S210325 https://www.dovepress.com/alternating-hemiplegia-of-childhood-understanding-the-genotypendashphe-peer-reviewed-article-TACG https://www.dovepress.com/alternating-hemiplegia-of-childhood-understanding-the-genotypendashphe-peer-reviewed-article-TACG

Yang X , Gao H , Zhang J , et al . ATP1A3 mutations and genotype-phenotype correlation of alternating hemiplegia of childhood in Chinese patients . PLoS One 2014 ; 9 ( 5 ): e97274 . doi: 10.1371/journal.pone.0097274 1001-9294-36-2-150/journal.pone.0097274 . DOI: 10.1371/journal.pone.0097274 http://doi.org/10.1371/journal.pone.0097274 https://dx.plos.org/10.1371/journal.pone.0097274 https://dx.plos.org/10.1371/journal.pone.0097274

Pisciotta L , Gherzi M , Stagnaro M , et al . Alternating hemiplegia of childhood: pharmacological treatment of 30 Italian patients . Brain Dev 2017 ; 39 ( 6 ): 521 - 8 . doi: 10.1016/j.braindev.2017.02.001 1001-9294-36-2-150/j.braindev.2017.02.001 . DOI: 10.1016/j.braindev.2017.02.001 http://doi.org/10.1016/j.braindev.2017.02.001 https://linkinghub.elsevier.com/retrieve/pii/S0387760417300281 https://linkinghub.elsevier.com/retrieve/pii/S0387760417300281

Sasaki M , Ishii A , Saito Y , et al . Genotype-phenotype correlations in alternating hemiplegia of childhood . Neurology 2014 ; 82 ( 6 ): 482 - 90 . doi: 10.1212/WNL.0000000000000102 1001-9294-36-2-150/WNL.0000000000000102 . DOI: 10.1212/WNL.0000000000000102 http://doi.org/10.1212/WNL.0000000000000102 http://www.neurology.org/cgi/doi/10.1212/WNL.0000000000000102 http://www.neurology.org/cgi/doi/10.1212/WNL.0000000000000102

Uchitel J , Helseth A , Prange L , et al . The epileptology of alternating hemiplegia of childhood . Neurology 2019 ; 93 ( 13 ): e1248 - e59 . doi: 10.1212/WNL.0000000000008159 1001-9294-36-2-150/WNL.0000000000008159 . DOI: 10.1212/WNL.0000000000008159 http://doi.org/10.1212/WNL.0000000000008159

Sasaki M , Ishii A , Saito Y , et al . Progressive brain atrophy in alternating hemiplegia of childhood . Mov Disord Clin Pract 2017 ; 4 ( 3 ): 406 - 11 . doi: 10.1002/mdc3.12451 1001-9294-36-2-150/mdc3.12451 . DOI: 10.1002/mdc3.12451 http://doi.org/10.1002/mdc3.12451 https://onlinelibrary.wiley.com/doi/10.1002/mdc3.12451 https://onlinelibrary.wiley.com/doi/10.1002/mdc3.12451

Jaffer F , Avbersek A , Vavassori R , et al . Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype . Brain 2015 ; 138 ( Pt 10 ): 2859 - 74 . doi: 10.1093/brain/awv243 1001-9294-36-2-150/brain/awv243 . DOI: 10.1093/brain/awv243 http://doi.org/10.1093/brain/awv243 https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awv243 https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awv243

Marzin P , Mignot C , Dorison N , et al . Early-onset encephalopathy with episodic movement disorders and epileptic seizures without hemiplegic attacks: about three children with novel ATP1A3 mutations . Brain Dev 2018 ; 40 ( 9 ): 768 - 74 . doi: 10.1016/j.braindev 1001-9294-36-2-150/j.braindev . DOI: 10.1016/j.braindev http://doi.org/10.1016/j.braindev https://linkinghub.elsevier.com/retrieve/pii/S0387760418302146 https://linkinghub.elsevier.com/retrieve/pii/S0387760418302146

Torres A , Brownstein CA , Tembulkar SK , et al . De novo ATP1A3 and compound heterozygous NLRP3 mutations in a child with autism spectrum disorder, episodic fatigue and somnolence, and muckle-wells syndrome . Mol Genet Metab Rep 2018 ; 16 : 23 - 9 . doi: 10.1016/j.ymgmr.2018.06.001 1001-9294-36-2-150/j.ymgmr.2018.06.001 . DOI: 10.1016/j.ymgmr.2018.06.001 http://doi.org/10.1016/j.ymgmr.2018.06.001

Smedemark-Margulies N , Brownstein CA , Vargas S , et al . A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia . Cold Spring Harb Mol Case Stud 2016 ; 2 ( 5 ): a001008 . doi: 10.1101/mcs.a001008 1001-9294-36-2-150/mcs.a001008 . DOI: 10.1101/mcs.a001008 http://doi.org/10.1101/mcs.a001008 http://molecularcasestudies.cshlp.org/lookup/doi/10.1101/mcs.a001008 http://molecularcasestudies.cshlp.org/lookup/doi/10.1101/mcs.a001008

Chaumette B , Ferrafiat V , Ambalavanan A , et al . Missense variants in ATP1A3 and FXYD gene family are associated with childhood-onset schizophrenia . Mol Psychiatry 2020 ; 25 ( 4 ): 821 - 30 . doi: 10.1038/s41380-018-0103-8 1001-9294-36-2-150/s41380-018-0103-8 . DOI: 10.1038/s41380-018-0103-8 http://doi.org/10.1038/s41380-018-0103-8 https://doi.org/10.1038/s41380-018-0103-8 https://doi.org/10.1038/s41380-018-0103-8

Panagiotakaki E , De Grandis E , Stagnaro M , et al . Clinical profile of patients with ATP1A3 mutations in alternating hemiplegia of childhood—a study of 155 patients . Orphanet J Rare Dis 2015 ; 10 : 123 . doi: 10.1186/s13023-015-0335-5 1001-9294-36-2-150/s13023-015-0335-5 . DOI: 10.1186/s13023-015-0335-5 http://doi.org/10.1186/s13023-015-0335-5

Paciorkowski AR , McDaniel SS , Jansen LA , et al . Novel mutations in ATP1A3 associated with catastrophic early life epilepsy, episodic prolonged apnea, and postnatal microcephaly . Epilepsia 2015 ; 56 ( 3 ): 422 - 30 . doi: 10.1111/epi.12914 1001-9294-36-2-150/epi.12914 . DOI: 10.1111/epi.12914 http://doi.org/10.1111/epi.12914

Pavlidis E , Uldall P , Gøbel Madsen C , et al . Alternating hemiplegia of childhood and a pathogenic variant of ATP1A3 : a case report and pathophysiological considerations . Epileptic Disord 2017 ; 19 ( 2 ): 226 - 30 . doi: 10.1684/epd.2017.0913 1001-9294-36-2-150/epd.2017.0913 . DOI: 10.1684/epd.2017.0913 http://doi.org/10.1684/epd.2017.0913

Jiang WJ , Chi ZF , Ma L , et al . Topiramate: a new agent for patients with alternating hemiplegia of childhood . Neuropediatrics 2006 ; 37 ( 4 ): 229 - 33 . doi: 10.1055/s-2006-924721 1001-9294-36-2-150/s-2006-924721 . DOI: 10.1055/s-2006-924721 http://doi.org/10.1055/s-2006-924721

Masoud M , Prange L , Wuchich J , et al . Diagnosis and treatment of alternating hemiplegia of childhood . Curr Treat Options Neurol 2017 ; 19 ( 2 ): 8 . doi: 10.1007/s11940-017-0444-7 1001-9294-36-2-150/s11940-017-0444-7 . DOI: 10.1007/s11940-017-0444-7 http://doi.org/10.1007/s11940-017-0444-7 http://link.springer.com/10.1007/s11940-017-0444-7 http://link.springer.com/10.1007/s11940-017-0444-7

Ju J , Hirose S , Shi XY , et al . Treatment with oral ATP decreases alternating hemiplegia of childhood with de novo ATP1A3 mutation . Orphanet J Rare Dis 2016 ; 11 ( 1 ): 55 . doi: 10.1186/s13023-016-0438-7 1001-9294-36-2-150/s13023-016-0438-7 . DOI: 10.1186/s13023-016-0438-7 http://doi.org/10.1186/s13023-016-0438-7 http://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0438-7 http://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0438-7

Dundar NO , Cavusoglu D , Kaplan YC , et al . An option to consider for alternating hemiplegia of childhood: aripiprazole . Clin Neuropharmacol 2019 ; 42 ( 3 ): 88 - 90 . doi: 10.1097/WNF.0000000000000339 1001-9294-36-2-150/WNF.0000000000000339 . DOI: 10.1097/WNF.0000000000000339 http://doi.org/10.1097/WNF.0000000000000339

Kramer PL , Mineta M , Klein C , et al . Rapid-onset dystonia-parkinsonism: linkage to chromosome 19q13 . Ann Neurol 1999 ; 46 ( 2 ): 176 - 82 . doi: 10.1002/1531-8249 1001-9294-36-2-150/1531-8249 (199908)46:2 < 176::aid-ana6 > 3.0.co;2-2. DOI: 10.1002/1531-8249 http://doi.org/10.1002/1531-8249

Haq IU , Snively BM , Sweadner KJ , et al . Revising rapid-onset dystonia-parkinsonism: broadening indications for ATP1A3 testing . Mov Disord 2019 ; 34 ( 10 ): 1528 - 36 . doi: 10.1002/mds.27801 1001-9294-36-2-150/mds.27801 . DOI: 10.1002/mds.27801 http://doi.org/10.1002/mds.27801 https://onlinelibrary.wiley.com/toc/15318257/34/10 https://onlinelibrary.wiley.com/toc/15318257/34/10

Wilcox R , Brænne I , Brüggemann N , et al . Genome sequencing identifies a novel mutation in ATP1A3 in a family with dystonia in females only . J Neurol 2015 ; 262 ( 1 ): 187 - 93 . doi: 10.1007/s00415-014-7547-9 1001-9294-36-2-150/s00415-014-7547-9 . DOI: 10.1007/s00415-014-7547-9 http://doi.org/10.1007/s00415-014-7547-9 http://link.springer.com/10.1007/s00415-014-7547-9 http://link.springer.com/10.1007/s00415-014-7547-9

Oblak AL , Hagen MC , Sweadner KJ , et al . Rapid-onset dystonia-parkinsonism associated with the I758S mutation of the ATP1A3 gene: a neuropathologic and neuroanatomical study of four siblings . Acta Neuropathol 2014 ; 128 ( 1 ): 81 - 98 . doi: 10.1007/s00401-014-1279-x 1001-9294-36-2-150/s00401-014-1279-x . DOI: 10.1007/s00401-014-1279-x http://doi.org/10.1007/s00401-014-1279-x http://link.springer.com/10.1007/s00401-014-1279-x http://link.springer.com/10.1007/s00401-014-1279-x

Yuan Y , Ran L , Lei L , et al . The expanding phenotypic spectrums associated with ATP1A3 mutation in a family with rapid-onset dystonia parkinsonism . Neurodegener Dis 2020 ; 20 : 84 - 9 . doi: 10.1159/000511733 1001-9294-36-2-150/000511733 . DOI: 10.1159/000511733 http://doi.org/10.1159/000511733 https://www.karger.com/Article/FullText/511733 https://www.karger.com/Article/FullText/511733

Demos MK , van Karnebeek CD , Ross CJ , et al . A novel recurrent mutation in ATP1A3 causes CAPOS syndrome . Orphanet J Rare Dis 2014 ; 9 : 15 . doi: 10.1186/1750-1172-9-15 1001-9294-36-2-150/1750-1172-9-15 . DOI: 10.1186/1750-1172-9-15 http://doi.org/10.1186/1750-1172-9-15 http://ojrd.biomedcentral.com/articles/10.1186/1750-1172-9-15 http://ojrd.biomedcentral.com/articles/10.1186/1750-1172-9-15

Heimer G , Sadaka Y , Israelian L , et al . CAOS—Episodic Cerebellar Ataxia, Areflexia, Optic Atrophy, and Sensorineural Hearing Loss: a third allelic disorder of the ATP1A3 gene . J Child Neurol 2015 ; 30 ( 13 ): 1749 - 56 . doi: 10.1177/0883073815579708 1001-9294-36-2-150/0883073815579708 . DOI: 10.1177/0883073815579708 http://doi.org/10.1177/0883073815579708 http://journals.sagepub.com/doi/10.1177/0883073815579708 http://journals.sagepub.com/doi/10.1177/0883073815579708

Dard R , Mignot C , Durr A , et al . Relapsing encephalopathy with cerebellar ataxia related to an ATP1A3 mutation . Dev Med Child Neurol 2015 ; 57 ( 12 ): 1183 - 6 . doi: 10.1111/dmcn.12927 1001-9294-36-2-150/dmcn.12927 . DOI: 10.1111/dmcn.12927 http://doi.org/10.1111/dmcn.12927 https://onlinelibrary.wiley.com/doi/10.1111/dmcn.12927 https://onlinelibrary.wiley.com/doi/10.1111/dmcn.12927

Hully M , Ropars J , Hubert L , et al . Mosaicism in ATP1A3-related disorders: not just a theoretical risk . Neurogenetics 2017 ; 18 ( 1 ): 23 - 8 . doi: 10.1007/s10048-016-0498-9 1001-9294-36-2-150/s10048-016-0498-9 . DOI: 10.1007/s10048-016-0498-9 http://doi.org/10.1007/s10048-016-0498-9 http://link.springer.com/10.1007/s10048-016-0498-9 http://link.springer.com/10.1007/s10048-016-0498-9

Yano ST , Silver K , Young R , et al . Fever-induced episodic weakness and encephalopathy, a new phenotype of ATP1A3 mutation . Pediatr Neurol 2017 ; 73 : 101 - 5 . doi: 10.1016/j.pediatrneurol.2017.04.022 1001-9294-36-2-150/j.pediatrneurol.2017.04.022 . DOI: 10.1016/j.pediatrneurol.2017.04.022 http://doi.org/10.1016/j.pediatrneurol.2017.04.022 https://linkinghub.elsevier.com/retrieve/pii/S0887899417301212 https://linkinghub.elsevier.com/retrieve/pii/S0887899417301212

Nakamura Y , Hattori A , Nakashima M , et al . A de novo p. Arg756Cys mutation in ATP1A3 causes a distinct phenotype with prolonged weakness and encephalopathy triggered by fever . Brain Dev 2018 ; 40 ( 3 ): 222 - 5 . doi: 10.1016/j.braindev.2017.09.010 1001-9294-36-2-150/j.braindev.2017.09.010 . DOI: 10.1016/j.braindev.2017.09.010 http://doi.org/10.1016/j.braindev.2017.09.010 https://linkinghub.elsevier.com/retrieve/pii/S0387760417302644 https://linkinghub.elsevier.com/retrieve/pii/S0387760417302644

Sabouraud P , Riquet A , Spitz MA , et al . Relapsing encephalopathy with cerebellar ataxia are caused by variants involving p. Arg756 in ATP1A3 . Eur J Paediatr Neurol 2019 ; 23 ( 3 ): 448 - 55 . doi: 10.1016/j.ejpn.2019.02.004 1001-9294-36-2-150/j.ejpn.2019.02.004 . DOI: 10.1016/j.ejpn.2019.02.004 http://doi.org/10.1016/j.ejpn.2019.02.004 https://linkinghub.elsevier.com/retrieve/pii/S1090379818304859 https://linkinghub.elsevier.com/retrieve/pii/S1090379818304859

Rosewich H , Weise D , Ohlenbusch A , et al . Phenotypic overlap of alternating hemiplegia of childhood and CAPOS syndrome . Neurology 2014 ; 83 ( 9 ): 861 - 3 . doi: 10.1212/WNL.0000000000000735 1001-9294-36-2-150/WNL.0000000000000735 . DOI: 10.1212/WNL.0000000000000735 http://doi.org/10.1212/WNL.0000000000000735

Hayashida T , Saito Y , Ishii A , et al . Further characterization of CAPOS/CAOS syndrome with the Glu818 Lys mutation in the ATP1A3 gene: a case report . Brain Dev 2018 ; 40 ( 7 ): 576 - 81 . doi: 10.1016/j.braindev.2018.03.004 1001-9294-36-2-150/j.braindev.2018.03.004 . DOI: 10.1016/j.braindev.2018.03.004 http://doi.org/10.1016/j.braindev.2018.03.004 https://linkinghub.elsevier.com/retrieve/pii/S0387760418300895 https://linkinghub.elsevier.com/retrieve/pii/S0387760418300895

Stenshorne I , Rasmussen M , Salvanos P , et al . Fever-related ataxia: a case report of CAPOS syndrome . Cerebellum Ataxias 2019 ; 6 : 2 . doi: 10.1186/s40673-019-0096-3 1001-9294-36-2-150/s40673-019-0096-3 . DOI: 10.1186/s40673-019-0096-3 http://doi.org/10.1186/s40673-019-0096-3

Schirinzi T , Graziola F , Nicita F , et al . Childhood rapid-onset ataxia: expanding the phenotypic spectrum of ATP1A3 mutations . Cerebellum 2018 ; 17 ( 4 ): 489 - 93 . doi: 10.1007/s12311-018-0920-y 1001-9294-36-2-150/s12311-018-0920-y . DOI: 10.1007/s12311-018-0920-y http://doi.org/10.1007/s12311-018-0920-y

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⁰

Alternating Hemiplegia of Childhood Caused by ATP1A3 Mutations: A Report of Two Cases

DOI：10.24920/003850

摘要

Abstract

关键词

Keywords

references