Lesch-Nyhan综合征8例临床特征及HPRT1基因变异分析

目的 分析Lesch-Nyhan综合征的临床特征及HPRT1基因变异特点,以提升对该病的认识。方法 回顾性分析2015年7月至2019年11月诊断并随访的8例患儿的临床表现、实验室检查及基因检测结果,总结患儿的临床特征及HPRT1基因变异特点。结果 8例患儿均为男性,于3月龄至11月龄起病,主因发育落后就诊,同时有锥体系及锥体外系症状,4例在就诊前已出现自残行为,4例目前尚未出现自残行为,血清尿酸不同程度增高。HPRT1基因检测出6种变异（c.609+5G>A、exon 2-3 del、c.131G>A、exon7-8 del、c.384+2T>A、c.212G>A）。经口服碳酸氢钠片、别嘌呤醇片、巴氯芬及家庭康复等治疗后,5例患儿脑损伤症状缓解,1例窒息死亡,1例死于肺部感染,1例未规律服药和复查,病情加重。结论 Lesch-Nyhan综合征患者的临床症状轻重不一,主要临床特征为神经系统功能障碍、自残行为、高尿酸血症,基因测序是确诊的关键,对症治疗可改善症状。     

婴儿期发病Lesch-Nyhan综合征4例临床表现及HPRT1基因突变分析并文献复习

目的 分析婴儿期发病Lesch-Nyhan综合征(LNS)患者临床特点以及相关基因突变情况.方法 对2017-2018年就诊于首都儿科研究所附属儿童医院的4例尿酸升高、运动发育迟缓、肌张力障碍伴或不伴有自残行为的婴儿患者进行全外显子基因检测,生物信息学分析筛选致病性变异,并对核心家系成员采用Sanger测序分析突变来源...     

HPRT1基因变异致Lesch-Nyhan综合征1例报告

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。     

多发性线粒体功能障碍综合征6 型1 例报告并文献复习

目的探讨PMPCB基因变异导致多发性线粒体功能障碍综合征6型(MMDS6)的临床表型和基因变异特点。方法回顾分析1例MMDS6患儿的临床资料,并结合文献进行复习。结果患儿,男,5月龄。表现为体质量不增、喂养困难、运动发育倒退、四肢肌张力低,伴高乳酸血症、心力衰竭。心脏彩超示肺动脉高压。全外显子和线粒体基因测序显示PMPCB基因c.524GA纯合核苷酸变异,父母均为杂合子,该纯合变异尚未见文献报道。结论 PMPCB基因c.524GA纯合核苷酸变异是MMDS6的致病变异。二代基因测序有助于基因型诊断。     

早期诊断Lesch-Nyhan综合征1例

正Lesch-Nyhan综合征(Lesch-Nyhan syndrome,LNS),又被称"自毁容貌综合征",因其特征性自伤行为而被熟知。典型LNS诊断较容易,但对于临床表现不典型的早期LNS或变异型LNS诊断仍较困难,需结合实验室检测等辅助检查结果综合考虑。本文报道1例LNS婴儿临床特点,为儿科医师诊断提供参考。1病历资料患儿男,10月龄。汉族。主因"10月龄竖头不稳"于2018-10-11入天津市儿童医院。患儿精神运动发育显著落后于同龄儿,4月龄曾可俯卧位抬头,后抬头逐渐变差,就诊时俯卧位尚不能抬头;     

Prader-Willi综合征1例

Prader-Willi综合征（Prader—Willi—Syndrome,PWS）是在1956年由Prader Cabbant和Willi描述并命名的,又称之为肌张力低下-智能障碍-性腺发育滞后-肥胖综合征,是一种遗传性疾病。在婴儿期突出表现为肌张力低下,极易与婴儿型脊髓性肌萎缩（SMA）、良性肌迟缓、大脑发育不全（软瘫型）相混淆。2000年注射用生长激素（HGH）被正式批准用于PWS的长期治疗,但多应用于儿童及成年人,婴幼儿少见报道,我们观察了1例生后7个月的女婴应用HGH治疗的情况。     

Bainbridge-Ropers综合征1例报告并文献复习

目的探讨Bainbridge-Ropers综合征的临床特点及遗传学特征。方法回顾分析1例Bainbridge-Ropers综合征患儿的临床资料,并复习相关文献。结果患儿,男,1岁1个月,以精神运动发育落后、喂养困难、肌张力低下及特殊面容为主要临床表现;全外显子基因测序显示ASXL3基因12号外显子c.3106CT(p.R1036*)杂合突变,确诊为BainbridgeRopers综合征。目前国内外文献共报道30余例,几乎所有患者存在运动、语言及智力发育迟缓,而且程度严重。结论Bainbridge-Ropers综合征是一种与ASXL3基因功能缺失突变有关的疾病,主要临床特征包括精神运动发育落后、喂养困难、肌张力低下及特殊面容。     

Williams综合征儿童早期运动发育特征

目的 分析Williams综合征(Williams syndrome,WS)儿童的早期运动发育情况,为临床早期干预提供依据。方法 对2018年9月至2021年8月间59例0～24月龄的WS儿童的临床资料进行回顾性分析,其中男40例,女19例。根据Peabody运动发育量表(Peabody Developmental Motor Scale Ⅱ)测试结果,分析不同年龄患儿的运动发育情况。结果 男女儿童月龄和运动商的比较差异均无统计学意义(P>0.05)。<6月龄组、6～<12月龄组、12～<18月龄组和18～24月龄组的粗大运动商分别为94±5、78±11、71±8、63±8,精细运动商分别为94±5、80±10、74±9、65±9,粗大运动商和精细运动商随着月龄增长逐渐下降(P<0.05)。<6月龄组、6～<12月龄组、12～<18月龄组和18～24月龄组的粗大运动发育异常率分别为0%、53%、87%、93%,精细运动发育异常率分别为0%、47%、67%、93%,粗大运动和精细运动发育异常率均随月龄增长而上升(P<0.05)。结论 ...     

The Lesch-Nyhan syndrome

Metabolic studies in a case of Lesch-Nyhan syndrome are presented. De novo synthesis of purine was shown to be inhibited upon adenine administration. The excretion of oxypurines is elevated, however, by an increased incorporation of the administered adenine into purine bases. A side effect of adenine administration is the production of the slightly soluble and highly nephrotoxic 2,8-dioxyadenine, which can cause renal damage.     

Atlantoaxial subluxation with recurrent consciousness disturbance in a boy with Lesch-Nyhan syndrome

Deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) may cause various clinical entities such as Lesch-Nyhan syndrome (LNS). A 9.5-y-old boy with the phenotypic features of LNS, including hyperuricaemia, choreoathetosis, self-mutilation and profound neurological dysfunction, was found to have HPRT deficiency. Normocytic anaemia, hyperuricaemia (uric acid 594.8 micromol/l) and microscopic haematuria with uric acid crystals were noted. Ultrasonography showed bilateral nephrocalcinosis and urinary bladder stones. In addition, he presented with three episodes of consciousness disturbance with limb paresis, possibly caused by atlantoaxial subluxation (AAS) with compression myelopathy. The diagnosis was made by the amount of residual enzyme activity and a single nucleotide substitution on the acceptor site region of intron 5 (IVS5-1 G-->C) of the HPRT gene, inherited from his asymptomatic mother. Conclusion: Lesch-Nyhan syndrome is a devastating sex-linked recessive disorder resulting from almost complete deficiency of the activity of HPRT. This report highlights the unusual AAS in a boy with LNS presenting recurrent consciousness change. The mutation described herein is a hitherto unreported splicing error leading to exon 6 skipping of the HPRT gene.     

儿童Lowe综合征OCRL基因突变2例报告

目的探讨儿童Lowe综合征的临床特点和基因特征。方法分析2例Lowe综合征患儿的临床资料和OCRL基因检测结果,并复习相关文献。结果 2例患儿均为男性,均存在小分子蛋白尿、高钙尿症、佝偻病和肾结石。例2患儿还有轻度代谢性酸中毒、糖尿和隐睾症。例1患儿生后不久发现有视力异常和先天性白内障,并行手术治疗,同时存在精神运动发育落后,头颅磁共振成像(MRI)示胼胝体发育不良。例2患儿就诊时肾外症状不明显,但眼科检查发现有先天性白内障,头颅MRI示脑发育低下、脑白质髓鞘化延迟,且随访过程中逐渐出现智力发育落后。OCRL基因检测发现2个突变,例1为剪切位点突变NG 008638.1:g.46846-46848del TAA/ins C,例2为缺失移码突变NM000276.3:c.321del C,两种突变以前文献均未报道。结论 Lowe综合征的诊断主要通过临床表现和OCRL基因检测,对于有先天性白内障、肾小管病变的患儿需要与Lowe综合征鉴别。本研究发现2个OCRL基因的新突变。     

Ruvalcaba syndrome: a case report

An 11-year-old child with mental retardation and short stature was examined and found to be affected with some skeletal malformations. The clinical and radiological pattern of limb alterations was particularly suggestive of the features of Ruvalcaba syndrome.A complete examination confirmed the diagnosis and showed ocular involvement. To the best of our knowledge this is first published confirmation of Ruvalcaba syndrome.Abbreviation VER visual evoked responses     

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目的报告1例肾病综合征、小头畸形、精神运动发育落后GallowayMowat综合征患儿,并进行文献复习。方法患儿(男,13岁)于2004年6月14日入院,根据病史、症状、体征、尿检、血清学及肾组织病理检查结果,结合文献进行分析。结果患儿以血尿、蛋白尿起病,小头畸形伴精神运动发育落后,后出现肾病综合征及肾功能不全,肾活检为局灶节段肾小球硬化。结论肾病综合征伴小头畸形、精神运动发育落后的患儿为GallowayMowat综合征,其肾病综合征出现越早预后越差。     

Hypoxanthine-guanine phosphoribosyltransferase gene analysis for Japanese patients with Lesch-Nyhan syndrome

The Lesch-Nyhan syndrome results as a consequence of a severe deficiency of functional activity of purine salvage enzyme, hypoxanthine phosphoribosyltransferase (HPRT). We performed Southern blot analysis for five patients and their families using full length cDNA of the HPRT gene as a probe. Pst I digested Southern blot analysis revealed a large deletion that included exon 2 in patient 3. The size of this deletion was about 4.4 Kb. The mother of this patient had the same mutated allele and a normal one (heterozygote). This type of mutation from a Lesch-Nyhan syndrome patient has not been previously reported. The restriction fragment length polymorphism (RFLP) pattern was analyzed by Bam HI digested Southern blot analysis for one family who had no major gene abnormality. We determined from this analysis that the sister of the patient was a Lesch-Nyhan syndrome carrier and the fetus (brother) was normal for HPRT activity. This study shows RFLP analysis is still useful for carrier detection and prenatal diagnosis of Lesch-Nyhan syndrome.     

Griscelli syndrome: a case report

A 10-year-old boy presented with partial albinism and typical clinical features of a macrophage activation syndrome (hepatosplenomegaly, fever, and pancytopenia), suggesting the diagnosis of Griscelli syndrome. The diagnosis was confirmed by light microscopic evaluation of hair that showed characteristic large aggregates of pigment granules irregularly distributed along the hair shaft. Immunosuppressive therapy controlled his macrophage activation syndrome successfully. Since early diagnosis is life saving and simple methods confirm the diagnosis, finding of partial albinism in children should alert clinicians to consider Griscelli syndrome.     

Mowat-Wilson综合征1例报告

目的探讨Mowat-Wilson综合征的临床特点。方法回顾分析1例Mowat-Wilson综合征患儿的临床资料及分子遗传学检测结果,并复习相关文献。结果患儿,女,3岁10个月,因智力运动发育迟缓及抽搐就诊;患儿面容特殊,前额突出、眼距宽、内眦赘皮、眉毛宽、鼻梁低、鼻小柱突出、下颌呈三角形、耳垂突出。心血管超声示二叶主动脉瓣;头部磁共振成像示双侧脑室轻度扩大;脑电图示额部、前颞导痫性放电。基因组测序及生物信息学分析显示患儿ZEB2基因3号外显子存在一处杂合突变c.164delC,导致氨基酸改变p.Pro55fs,确诊为Mowat-Wilson综合征。结论扩充了中国Mowat-Wilson综合征患者ZEB2基因突变谱。