罕见病 疑难病

HPRT1基因变异致Lesch-Nyhan综合征1例报告

  • 李逢潮 ,
  • 章印红 ,
  • 吕涛 ,
  • 朱宝生 ,
  • 韩思琪 ,
  • 蔡世岩 ,
  • 李利
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  • 1.昆明理工大学医学院(云南昆明 650500
    2.云南省第一人民医院儿科(云南昆明 650032
    3.云南省第一人民医院医学遗传科(云南昆明 650032
    4.昆明理工大学附属医院(云南昆明 650500

收稿日期: 2021-06-22

  网络出版日期: 2022-06-07

基金资助

云南省万人计划“名医”专项(2018);云南省出生缺陷与罕见病临床医学研究中心(2019ZF015);云南省出生缺陷与遗传病重点实验室

Lesch-Nyhan syndrome caused by HPRT1 gene variation: a case report

  • Fengchao LI ,
  • Yinhong ZHANG ,
  • Tao LYU ,
  • Baosheng ZHU ,
  • Siqi HAN ,
  • Shiyan CAI ,
  • Li LI
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  • 1. Medical School, Kunming University of Science and Technology, Kunming 650500, Yunnan, China
    2. Department of Pediatrics, Yunnan First People’s Hospital, Kunming 650032, Yunnan, China
    3. Medical Genetics Department, Yunnan First People’s Hospital, Kunming 650032, Yunnan, China
    4. The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650500, Yunnan, China

Received date: 2021-06-22

  Online published: 2022-06-07

摘要

Lesch-Nyhan综合征是一种罕见的X连锁隐性遗传病,在自伤行为出现前,易被误诊为脑瘫,延误诊治。先证者,男,8岁7个月,因发育落后8年余,肌张力异常就诊。多次血生化均提示尿酸增高,遗传学分析结果证实患儿为HPRT1基因c.200_201delTG变异,经ACMG评级为疑似致病性变异,Sanger测序验证发现该变异遗传自患儿母亲,为未报道的新变异,从而确诊为HPRT1基因相关Lesch-Nyhan综合征,口服别嘌醇片、碳酸氢钠片6月后尿酸水平较前明显下降,仍无自伤行为。临床上遇到不明原因脑瘫表现者,应及早行遗传学检查,以帮助早期诊断和遗传咨询。

本文引用格式

李逢潮 , 章印红 , 吕涛 , 朱宝生 , 韩思琪 , 蔡世岩 , 李利 . HPRT1基因变异致Lesch-Nyhan综合征1例报告[J]. 临床儿科杂志, 2022 , 40(6) : 465 -468 . DOI: 10.12372/jcp.2022.21e0944

Abstract

Lesch-Nyhan syndrome is a rare X-linked recessive genetic disease. Before the occurrence of self-injury, it could be misdiagnosed as cerebral palsy. The proband, male, 8 years and 7 months old, was admitted to the clinic due to over 8 years of developmental retardation and abnormal muscle tone. Multiple blood biochemical tests showed that uric acid was increased. Genetic analysis results confirmed that the patient had c.200 _ 201delTG variation of HPRT1 gene, which was rated as a suspected pathogenic variation by ACMG. Sanger sequencing confirmed that the variation was inherited from the mother and was an unreported new variation, thus the child was diagnosed with HPRT1 gene-associated Lesch-Nyhan syndrome. After oral allopurinol tablets and sodium bicarbonate tablets for 6 months, the level of uric acid decreased significantly, and there was no self-injury behavior. In patients with unexplained cerebral palsy, genetic examination should be performed as early as possible to help early diagnosis and genetic counseling.

参考文献

[1] Harris JC. Lesch-Nyhan syndrome and its variants: examining the behavioral and neurocognitive phenotype[J]. Curr Opin Psychiatry, 2018, 31(2): 96-102.
[2] Nguyen KV, Nyhan WL. Mutation in the Human HPRT1 Gene and the Lesch-Nyhan Syndrome[J]. Nucleosides Nucleotides Nucleic Acids, 2016, 35(8): 426-433.
[3] Richards S, Aziz N, Bale S, et al. 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(5): 405-424.
[4] Cho JH, Choi JH, Sun HH, et al. Phenotypic and molecular spectrum of Korean patients with Lesch-Nyhan syndrome and attenuated clinical variants[J]. Metab Brain Dis, 2019, 34(5): 1335-1340.
[5] Fu R, Ceballos-Picot I, Torres RJ, et al. Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder[J]. Brain, 2014, 137: 1282-1303.
[6] 田小娟, 丁昌红, 代丽芳, 等. HPRT1基因突变致Lesch-Nyhan综合征1例临床特点及基因分析[J]. 中华实用儿科临床杂志, 2019, 34(18): 1424-1426.
[7] Ambarsari CG, Cahyadi D, Sari L, et al. Late diagnosis of Lesch-Nyhan disease complicated with end-stage renal disease and tophi burst: a case report[J]. Ren Fail, 2020, 42(1): 113-121.
[8] Bell S, Kolobova I, Crapper L, et al. Lesch-Nyhan Syndrome: Models, Theories, and Therapies[J]. Mol Syndromol, 2016, 7(6): 302-311.
[9] Mishima E, Mori T, Nakajima Y, et al. HPRT-related hyperuricemia with a novel p.V35M mutation in HPRT1 presenting familial juvenile gout[J]. CEN Case Rep, 2020, 9(3): 210-214.
[10] Cakmakli HF, Torres RJ, Menendez A, et al. Macrocytic anemia in Lesch-Nyhan disease and its variants[J]. Genet Med, 2019, 21(2): 353-360.
[11] Salhotra R, Sharma C, Tyagi A, et al. An unanticipated difficult airway in Lesch-Nyhan syndrome[J]. J Anaesthesiol Clin Pharmacol, 2012, 28(2): 239-241.
[12] Torres RJ, Puig JG, Jinnah HA. Update on the phenotypic spectrum of lesch-nyhan disease and its attenuated variants[J]. Curr Rheumatol Rep, 2012, 14(2): 189-194.
[13] 中华医学会内分泌学分会. 中国高尿酸血症与痛风诊疗指南(2019)[J]. 中华内分泌代谢杂志, 2020, 36(1): 1-13.
[14] Jacomelli G, Baldini E, Mugnaini C, et al. Inhibiting PNP for the therapy of hyperuricemia in Lesch-Nyhan disease: Preliminary in vitro studies with analogues of immucillin[J]. J Inherit Metab Dis, 2019, 42(1): 178-185.
[15] Pozzi M, Piccinini L, Gallo M, et al. Treatment of motor and behavioural symptoms in three Lesch-Nyhan patients with intrathecal baclofen[J]. Orphanet J Rare Dis, 2014, 9(1): 208.
[16] Khasnavis T, Torres RJ, Sommerfeld B, et al. A double-blind, placebo-controlled, crossover trial of the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease[J]. Mol Genet Metab, 2016, 118(3):160-166.
[17] Chen BC, Balasubramaniam S, McGown IN, et al. Treatment of Lesch-Nyhan disease with S-adeno-sylmethionine: experience with five young Malaysians, including a girl[J]. Brain Dev, 2014, 36(7): 593-600.
[18] Tambirajoo K, Furlanetti L, Hasegawa H, et al. Deep brain stimulation of the internal pallidum in Lesch-Nyhan syndrome: clinical outcomes and connectivity analysis[J]. Neuromodulation, 2020, 24(2):380-391.
[19] Gilbert C, Sauer M, Cheng J. Reduction of self-mutilating behavior and improved oromotor function in a patient with Lesch-Nyhan syndrome following botulinum toxin injection: A case report[J]. J Pediatr Rehabil Med, 2021, 14(1): 133-136.
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