过氧化物酶体酰基辅酶A氧化酶缺乏症一例并文献复习

doi:10.3969/j.issn.1672-6731.2021.04.009

中国现代神经疾病杂志 ›› 2021, Vol. 21 ›› Issue (4): 281-288. doi: 10.3969/j.issn.1672-6731.2021.04.009

• 神经病理与人脑组织库建设 • 上一篇下一篇

2 过氧化物酶体酰基辅酶A氧化酶缺乏症一例并文献复习

尤桦菁¹, 田杨², 李洵桦¹, 李小晶², 裴中¹

1 510080 广州, 中山大学附属第一医院神经科广东省重大神经疾病诊治研究重点实验室国家临床重点专科和国家重点学科;
2 510623 广东省广州市妇女儿童医疗中心神经内科

收稿日期:2021-04-16 出版日期:2021-04-25 发布日期:2021-04-27
通讯作者: 裴中,Email:peizhong@mail.sysu.edu.cn
基金资助:
国家重点研发计划项目（项目编号：2017YFA0105104）；国家自然科学基金资助项目（项目编号：81873751）；国家自然科学基金资助项目（项目编号：82071255）；华南神经疾病早期干预及功能修复研究国际合作基地（项目编号：2015B050501003）；广东省神经系统重大疾病诊治工程项目；广东省神经系统重大疾病诊治转化医学创新平台项目；广东省神经系统疾病临床医学研究项目

Peroxisomal acyl-CoA oxidase deficiency: one case report and literature review

YOU Hua-jing¹, TIAN Yang², LI Xun-hua¹, LI Xiao-jing², PEI Zhong¹

1 Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University;Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases;National Key Clinical Department and Key Discipline of Neurology, Guangzhou 510080, Guangdong, China;
2 Department of Neurology, Guangzhou Women and Children's Medical Center, Guangzhou 510623, Guangdong, China

Received:2021-04-16 Online:2021-04-25 Published:2021-04-27
Supported by:
This study was supported by the National Key Research and Development Program of China, Stem Cell and Translational Research (No. 2017YFA0105104), the National Natural Science Foundation of China (No. 81873751, 82071255), the Southern China International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases (No. 2015B050501003), Guangdong Provincial Engineering Center for Major Neurological Disease Treatment, Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease, and Guangdong Provincial Clinical Research Center for Neurological Diseases.

摘要/Abstract

摘要：

目的首次报道1例国内ACOX1基因突变致过氧化物酶体酰基辅酶A氧化酶缺乏症患儿，结合文献综述其临床特征。方法与结果 男性患儿，出生时肌张力偏低、生长发育迟缓并出现抽搐发作1次，3岁时出现神经功能退化并快速进展至无法独坐、独自站立和行走，语言表达能力倒退；体格检查可见特殊面容、锥体束征及小脑损害。头部MRI显示双侧脑干和小脑对称性脱髓鞘改变；血清极长链脂肪酸（VLCFAs）水平升高。全外显子组测序，患儿存在ACOX1基因c.1589A > G（p.His530Arg）纯合突变，其父母均携带ACOX1基因c.1589A > G（p.His530Arg）杂合突变，但无临床症状，符合家系共分离现象；根据美国医学遗传学和基因组学会（ACMG）指南，该变异为可能致病突变。患儿最终诊断为过氧化物酶体酰基辅酶A氧化酶缺乏症。结论对于新生儿期发病的肌张力低下、癫发作和生长发育迟缓，若头部MRI显示小脑、脑干等对称性异常信号，应高度警惕过氧化物酶体病，阳性家族史、VLCFAs水平升高和基因检测可明确诊断。

关键词: 过氧化物酶体类, 酰基CoA氧化酶, 基因, 突变

Abstract:

Objective To report a case of peroxisomal acyl-CoA oxidase (ACOX1) deficiency, which was caused by an unreported mutation of ACOX1 gene, and review its clinical characteristics. Methods and Results The male child patient suffered from neonatal hypotonia，developmental retardation and epilepsy seizure once since neonatal period. Neurodegeneration appeared at the age of 3 and developed rapidly to difficulty of sitting, standing and walking independently and retrogressive language expression ability. Physical examination showed special face, pyramidal tract sign and cerebellar signs. Cranial MRI revealed symmetric demyelinating lesions in bilateral brain stem and cerebellum along with increased serum very-long-chain fatty acids (VLCFAs). Whole exome sequencing revealed c. 1589A > G (p. His530Arg) homozygous mutation in ACOX1 gene. His parents carried the same heterozygous mutation without symptoms and this phenomenon was in accord with co-segregation. According to the guidelines of American College of Medical Genetics and Genomics (ACMG), we considered this new variation to be possibly pathogenic variation. Finally, the patient was diagnosed as ACOX1 deficiency. Conclusions As for patients who suffer from hypotonia, epilepsy seizure and growth retardation since neonatal period, they should be altered to ACOX1 deficiency if cranial MRI shows symmetrical abnormal foci in cerebellum and brain stem. Positive family history, increased VLCFAs level, and gene detection would be beneficial to definite diagnosis.

Key words: Peroxisomes, Acyl-CoA oxidase, Genes, Mutation

尤桦菁, 田杨, 李洵桦, 李小晶, 裴中. 过氧化物酶体酰基辅酶A氧化酶缺乏症一例并文献复习[J]. 中国现代神经疾病杂志, 2021, 21(4): 281-288.

YOU Hua-jing, TIAN Yang, LI Xun-hua, LI Xiao-jing, PEI Zhong. Peroxisomal acyl-CoA oxidase deficiency: one case report and literature review[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2021, 21(4): 281-288.

http://journal11.magtechjournal.com/cjcnn/CN/Y2021/V21/I4/281

参考文献

[1] Poll-The BT, Roels F, Ogier H, Scotto J, Vamecq J, Schutgens RB, Wanders RJ, van Roermund CW, van Wijland MJ, Schram AW. A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy)[J]. Am J Hum Genet, 1988, 42:422-434.
[2] Fournier B, Saudubray JM, Benichou B, Lyonnet S, Munnich A, Clevers H, Poll-The BT. Large deletion of the peroxisomal acyl-CoA oxidase gene in pseudoneonatal adrenoleukodystrophy[J]. J Clin Invest, 1994, 94:526-531.
[3] Morita A, Enokizono T, Ohto T, Tanaka M, Watanabe S, Takada Y, Iwama K, Mizuguchi T, Matsumoto N, Morita M, Takashima S, Shimozawa N, Takada H. Novel ACOX1 mutations in two siblings with peroxisomal acyl-CoA oxidase deficiency[J]. Brain Dev, 2021, 43:475-481.
[4] Ferdinandusse S, Denis S, Hogenhout EM, Koster J, van Roermund CW, IJlst L, Moser AB, Wanders RJ, Waterham HR. Clinical, biochemical, and mutational spectrum of peroxisomal acyl-coenzyme A oxidase deficiency[J]. Hum Mutat, 2007, 28:904-912.
[5] Ferdinandusse S, Barker S, Lachlan K, Duran M, Waterham HR, Wanders RJ, Hammans S. Adult peroxisomal acyl-coenzyme A oxidase deficiency with cerebellar and brainstem atrophy[J]. J Neurol Neurosurg Psychiatry, 2010, 81:310-312.
[6] Suzuki Y, Shimozawa N, Yajima S, Tomatsu S, Kondo N, Nakada Y, Akaboshi S, Lai M, Tanabe Y, Hashimoto T. Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein:identification by means of complementation analysis[J]. Am J Hum Genet, 1994, 54:36-43.
[7] Ferdinandusse S, Denis S, Mooijer PA, Zhang Z, Reddy JK, Spector AA, Wanders RJ. Identification of the peroxisomal beta-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid[J]. J Lipid Res, 2001, 42:1987-1995.
[8] Su HM, Moser AB, Moser HW, Watkins PA. Peroxisomal straight-chain Acyl-CoA oxidase and D-bifunctional protein are essential for the retroconversion step in docosahexaenoic acid synthesis[J]. J Biol Chem, 2001, 276:38115-38120.
[9] Wang RY, Monuki ES, Powers J, Schwartz PH, Watkins PA, Shi Y, Moser A, Shrier DA, Waterham HR, Nugent DJ, Abdenur JE. Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency:a sibling comparison study[J]. J Inherit Metab Dis, 2014, 37:791-799.
[10] Eichler F, Duncan C, Musolino PL, Orchard PJ, De Oliveira S, Thrasher AJ, Armant M, Dansereau C, Lund TC, Miller WP, Raymond GV, Sankar R, Shah AJ, Sevin C, Gaspar HB, Gissen P, Amartino H, Bratkovic D, Smith NJC, Paker AM, Shamir E, O'Meara T, Davidson D, Aubourg P, Williams DA. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy[J]. N Engl J Med, 2017, 377:1630-1638.
[11] Watkins PA, McGuinness MC, Raymond GV, Hicks BA, Sisk JM, Moser AB, Moser HW. Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficiencies[J]. Ann Neurol, 1995, 38:472-477.
[12] Chen WW, Watkins PA, Osumi T, Hashimoto T, Moser HW. Peroxisomal beta-oxidation enzyme proteins in adrenoleukodystrophy:distinction between X-linked adrenoleukodystrophy and neonatal adrenoleukodystrophy[J]. Proc Natl Acad Sci USA, 1987, 84:1425-1428.
[13] Masson R, Guerra S, Cerini R, Pensato V, Gellera C, Taroni F, Simonati A. Early white matter involvement in an infant carrying a novel mutation in ACOX1[J]. Eur J Paediatr Neurol, 2016, 20:431-434.
[14] Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; 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[J]. Genet Med, 2015, 17:405-424.
[15] Suzuki Y, Iai M, Kamei A, Tanabe Y, Chida S, Yamaguchi S, Zhang Z, Takemoto Y, Shimozawa N, Kondo N. Peroxisomal acyl CoA oxidase deficiency[J]. J Pediatr, 2002, 140:128-130.
[16] De Munter S, Verheijden S, Régal L, Baes M. Peroxisomal disorders:a review on cerebellar pathologies[J]. Brain Pathol, 2015, 25:663-678.
[17] Kurian MA, Ryan S, Besley GT, Wanders RJ, King MD. Straight-chain acyl-CoA oxidase deficiency presenting with dysmorphia, neurodevelopmental autistic-type regression and a selective pattern of leukodystrophy[J]. J Inherit Metab Dis, 2004, 27:105-108.
[18] Wanders RJ, Schelen A, Feller N, Schutgens RB, Stellaard F, Jakobs C, Mitulla B, Seidlitz G. First prenatal diagnosis of acyl-CoA oxidase deficiency[J]. J Inherit Metab Dis, 1990, 13:371-374.
[19] Schutgens RB, Schrakamp G, Wanders RJ, Heymans HS, Tager JM, van den Bosch H. Prenatal and perinatal diagnosis of peroxisomal disorders[J]. J Inherit Metab Dis, 1989, 12 Suppl 1:118-134.

选择文件类型/文献管理软件名称

选择包含的内容

2 过氧化物酶体酰基辅酶A氧化酶缺乏症一例并文献复习

Peroxisomal acyl-CoA oxidase deficiency: one case report and literature review

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	任修德, 李涛, 范吉康, 王希森, 贾晓丹, 杨学军. 胶质母细胞瘤FGFR3-TACC3融合基因介导丙酮酸激酶M2入核促进DNA损伤修复基础研究[J]. 中国现代神经疾病杂志, 2023, 23(8): 745-757.
[2]	吴旭玲, 张安妮, 雷晓阳, 冯占辉, 王维, 贺电. 强直性肌营养不良症1型一例[J]. 中国现代神经疾病杂志, 2023, 23(8): 765-769.
[3]	李跃文, 褚先舟, 李娟, 秦艳, 吴桐, 陈先文. BSCL2基因c.455A>G突变致远端型遗传性运动神经病V型一家系[J]. 中国现代神经疾病杂志, 2023, 23(7): 643-647.
[4]	杜倩, 邓素君, 邹姗, 金珺, 周青山. 宏基因组第二代测序技术在重症中枢神经系统感染中的应用[J]. 中国现代神经疾病杂志, 2023, 23(6): 479-484.
[5]	崔立立, 纪坤乾, 张正华, 张同霞, 赵玉英. 以排尿困难发病的SOD1基因变异致肌萎缩侧索硬化一例[J]. 中国现代神经疾病杂志, 2023, 23(5): 472-476.
[6]	蔡洪钱, 张安妮, 徐子茜, 龚慧蓝, 曾红梅, 贺电. 伴PSEN2基因V214L突变的早发型阿尔茨海默病一家系临床研究[J]. 中国现代神经疾病杂志, 2023, 23(4): 335-340.
[7]	徐蓉, 宁泽淑, 康庆云, 陈波, 廖红梅, 杨理明, 吴丽文. 钾离子通道基因变异相关婴儿癫痫性脑病临床表型与基因变异特点分析[J]. 中国现代神经疾病杂志, 2023, 23(3): 196-204.
[8]	唐薇婷, 肖波. N-甲基-D-天冬氨酸受体GRIN2A基因变异与癫痫研究进展[J]. 中国现代神经疾病杂志, 2023, 23(2): 89-93.
[9]	李字林, 胡文瀚, 张凯. 癫痫外科常见病理类型体细胞突变研究进展[J]. 中国现代神经疾病杂志, 2023, 23(2): 115-123.
[10]	姚盈盈, 王雷明, 滕梁红. 脑胶质瘤DNA甲基化临床意义及研究进展[J]. 中国现代神经疾病杂志, 2022, 22(9): 823-828.
[11]	夏钰, 沙倩倩, 朱雯华, 乔凯, 都爱莲. SCN4A基因R672G位点突变致低钾性周期性瘫痪伴肌萎缩一家系分析并文献复习[J]. 中国现代神经疾病杂志, 2022, 22(8): 717-722.
[12]	万雅兰, 蒋岩岩, 周红, 郑艺明, 吕鹤, 赵桂萍, 陈静, 孙葳, 王朝霞. 表现为帕金森综合征的脊髓小脑性共济失调2型两家系并文献复习[J]. 中国现代神经疾病杂志, 2022, 22(8): 723-728.
[13]	张梓枫, 周政旭, 唐文天, 洪汛宁, 王协锋, 程刚, 刘宁, 鲁艾林, 张军霞, 尤永平. IDH突变型岛叶胶质瘤MRI特征预测因素分析[J]. 中国现代神经疾病杂志, 2022, 22(5): 404-413.
[14]	许保磊, 陈彪. 帕金森病细胞移植治疗和基因治疗进展[J]. 中国现代神经疾病杂志, 2022, 22(4): 243-252.
[15]	刘晓黎, 张斌, 詹飞霞, 曹立. 肾上腺脊髓神经病五例临床表型及遗传学分析[J]. 中国现代神经疾病杂志, 2022, 22(4): 306-312.

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

2 过氧化物酶体酰基辅酶A氧化酶缺乏症一例并文献复习

Peroxisomal acyl-CoA oxidase deficiency: one case report and literature review

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价