Children of birth weight less than 1000 g: changing outcome between ages 2 and 5 years

Of 55 consecutive long-term survivors of birth weight 500 to 999 g, complete psychologic and pediatric data were available for 54 children at 2 years corrected age and for 50 at age at least 5 1/2 years. At the latter age, 60% (30 of 50) were not impaired, 10% (five of 50) had severe sensorineural or intellectual impairments, 10% (five of 50) had mild to moderately impairment, and 20% (10 of 50) had minor neurobehavioural abnormalities. Sensorineural deafness in one child and bilateral blindness in one remained stable over time, but of six children with spastic cerebral palsy at 2 years, only three retained this diagnosis at 5 1/2 years. The mean Mental Developmental Index (MDI) on the Bayley Scales at 2 years was 91.1, significantly below the test mean; by 5 1/2 years the mean full scale of the Wechsler Preschool and Primary Scales of Intelligence (WPPSI) was 101.8. The MDI correlated highly with the full-scale WPPSI (r = 0.7), but for individual children it was not always an accurate predictor of 5-year ability. Between 2 and 5 1/2 years there was a substantial reordering within four categories of impairment: findings in 27 children were improved, four were judged to become more severely impaired over time, and 19 did not change. We conclude that our 2-year assessment often underrated the potential of the children as expressed at 5 1/2 years, and that 2 years is too early for reliable classification of children of birth weight 500 to 999 g.     

13例早发型腓骨肌萎缩症的基因分型研究

目的 探讨早发型腓骨肌萎缩症（CMT）的临床特征及遗传变异分析。方法 以临床诊断为早发型CMT的患儿为研究对象，收集相关临床资料，进行肌电图及CMT相关基因检测并分析。结果 早发型CMT病例共13例，男9例（69%），女4例（31%），平均就诊年龄4.0±2.1岁，其中12例（92%）患儿起病年龄 < 2岁。9例（69%）诊断为CMT1型（其中Dejerine-Sottas综合征6人），1例（8%）为中间型，3例（23%）为CMT2型。13例患儿的基因检测结果显示6例（46%）患儿存在外周髓鞘蛋白22（PMP22）基因重复突变、3例（23%）髓鞘蛋白零（MPZ）基因插入突变及点突变、3例（23%）线粒体融合蛋白2（MFN2）基因点突变、1例（8%）人轻肽神经丝蛋白（NEFL）基因点突变，其中11例（85%）为已知致病突变，2例（15%）为新变异。MPZ基因新变异c.394C > G（p.P132A）评级为"可能致病的"及MFN2基因新变异c.326A > G（p.K109R）评级为"致病的"。结论 早发型CMT以PMP22基因重复突变及MPZ基因突变为主，临床分型以CMT1型为主，其中Dejerine-Sottas综合征占有相当比例。     

Mild form of Hunter's syndrome: clinical delineation based on 31 cases.

The clinical features are described in 31 cases of the mild form of Hunter''s syndrome (mucopolysaccharidosis II) ascertained in the British Isles. The mean age at onset was 4.3 years and at death was 21.7 years. Each patient had a large head and short stature. Umbilical and inguinal herniae were recorded in 95% and 61% of the cases. Evidence of cardiac disease was found in 91%; this was the most common cause of death. All of the patients suffered from frequent upper or lower respiratory tract infection. Middle airways obstruction proved to be a particular hazard. A high incidence of sensorineural deafness and unexplained papilloedema was noted. The importance of regular health care for these individuals is stressed.     

Visual impairment in severe and profound sensorineural deafness

The frequency of reversible and irreversible visual impairment was determined in children with severe and profound sensorineural deafness, as subnormal vision can adversely affect their educational and social development. Eighty three of 87 such children attending an audiology service were examined to assess the incidence and severity of visual impairment. Each child underwent a detailed ophthalmic assessment. The criteria for visual impairment were visual acuity < 6/9 Snellen or equivalent and/or abnormal binocular vision. Forty five had a normal ophthalmic examination (54.2%). Twenty nine had visual impairment (34.9%) and nine had ophthalmological abnormalities that did not interfere with vision (10.9%). A higher proportion of children with risk factors for visual pathology demonstrated visual impairment than those in whom there were no risk factors. None the less, 44% of visual impairment was among patients without risk factors. The results underline the need to examine all children with severe and profound sensorineural deafness soon after diagnosis and indicate that children with multiple handicaps have a greater likelihood of visual impairment (11 of 14 cases).     

Visual impairment in severe and profound sensorineural deafness.

The frequency of reversible and irreversible visual impairment was determined in children with severe and profound sensorineural deafness, as subnormal vision can adversely affect their educational and social development. Eighty three of 87 such children attending an audiology service were examined to assess the incidence and severity of visual impairment. Each child underwent a detailed ophthalmic assessment. The criteria for visual impairment were visual acuity < 6/9 Snellen or equivalent and/or abnormal binocular vision. Forty five had a normal ophthalmic examination (54.2%). Twenty nine had visual impairment (34.9%) and nine had ophthalmological abnormalities that did not interfere with vision (10.9%). A higher proportion of children with risk factors for visual pathology demonstrated visual impairment than those in whom there were no risk factors. None the less, 44% of visual impairment was among patients without risk factors. The results underline the need to examine all children with severe and profound sensorineural deafness soon after diagnosis and indicate that children with multiple handicaps have a greater likelihood of visual impairment (11 of 14 cases).     

Auditory profile in children recovering from bacterial meningitis

In the present study BERA profile of 30 post-meningitic children was compared with 15 normal children of the same age and it was observed that 36.6% children in the age range of 6 months to 36 months were found to have varying degree of sensorineural deafness. Severe bilateral sensorineural hearing loss (>80 dB) was observed in 6.6% children and moderate (40–80 dB) hearing loss in 30% of children. Abnormalities were bilateral in both the samples of children with severe hearing loss (>80 dB) whereas among 9 children who had moderate hearing loss abnormalities were bilateral in one patient and unilateral in the remaining 8 children. A relationship between higher incidence of sensorineural deafness and younger age of children, and occurence of seizures during meningitis were noted. But no relationship was observed with either sex, hydrocephalus, subdural effusion or with low CSF sugar and high CSF proteins.     

Congenital cytomegalovirus infection: a cause of sensorineural hearing loss.

Prospective studies have suggested that about 108 children with congenital cytomegalovirus (CMV) infection and bilateral sensorineural hearing loss are born each year in England and Wales; this represents about 12% of all children with congenital sensorineural hearing loss. Over a nine year period 1644 children aged between 6 months and 4 years who were attending the Nuffield Hearing and Speech Centre were screened for CMV infection. The prevalence of CMV in the urine of children with sensorineural hearing loss but no immediate family history of deafness was nearly twice that (13%) found in other children with impaired hearing and those with normal hearing (7%). These findings indicate the importance of CMV as a cause of hearing loss.     

Hearing loss in children with osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue. Progressive hearing loss is one of the principal symptoms of OI, affecting about 50% of adult patients. Hearing loss may also occur in childhood and results in additional disability in education and psychosocial adaptation and aggravates the physical handicap. This can be avoided by appropriate otological and audiological treatment. In a nationwide search, 254 Finnish patients with OI were identified indicating a prevalence of 4.9/100 000. Of the 60 children, 45 aged between 4 and 16 years accepting to participate the study on hearing, were evaluated by a questionnaire and clinical audiometry. Hearing loss was defined as pure tone average (PTA_{0.5–2 kHz}) more than 20 dB hearing level (HL). A clinical geneticist determined the type of OI among the 45 patients. Two sporadic OI cases with conductive hearing loss were ascertained (4.4%): An 11-year-old girl with type IV OI with a PTA_{0.5–2 kHz} of 35/40 dB HL and a 15-year-old boy with type IV OI with a PTA_{0.5–2 kHz} of 27/18 dB HL. In addition, a 6-year-old girl with familial OI type I had either a congenital sensorineural deafness or early progressive deafness with PTA_{0.5–2 kHz} of 97/103 dB HL, probably of unrelated aetiology. Conclusion Hearing loss in children with osteogenesis imperfecta is less frequent than generally suspected. Nevertheless, it is recommended that audiometry is performed in children with osteogenesis imperfecta even without symptoms of hearing loss at the age of 10 years, and repeated every 3 years thereafter. Received: 13 October 1999 and in revised forms: 20 December 1999, 13 January 2000 and 24 January 2000 / Accepted: 25 January 2000     

Hearing loss in facioscapulohumeral dystrophy

Bilateral sloping high frequency hearing loss of 20–90 dB was found in six out of ten patients with infantile or adolescent onset FSHD. In all cases the basic defect could be traced to the cochlea. The outer hair cells of the basal turn are predominantly affected. In 20 patients with various other forms of muscular dystrophy or neuromuscular disorders with an FSH distribution, no sensorineural hearing loss was found. Myopathology of FSHD patients extended from mild to severe, often showing inflammatory infiltrates and type I fibre atrophy, without unequivocal differences between the two groups with and without hearing loss. It is concluded that cochlear dysfunction is a specific and frequenct phenomenon of early onset FSHD.Abbreviations FSH facioscapulohumeral - FSHD facioscapulohumeral dystrophy - MD muscular dystrophy - SISI short increment sensitivity index     

13例Wiskott-Aldrich综合征临床特征分析

目的 研究Wiskott-Aldrich综合征（WAS）患儿的临床特征。方法 对13例WAS患儿的临床资料进行回顾性分析。结果 13例患儿均为男性,发病年龄3（1~48）月,确诊年龄24（1~60）月。13例患儿中仅3例为典型WAS,余10例均为X-连锁血小板减少症（XLT）。WAS评分为2（1~3）分,血小板计数为20.5（13~46）×10⁹/L,平均血小板体积为8.1（6.7~12.1） fl。4例患儿行淋巴细胞亚群及免疫球蛋白检查,其中淋巴细胞占有核细胞百分比及CD3⁺T细胞占淋巴细胞百分比均减低者1例（25%）;CD3^-CD56⁺NK细胞占淋巴细胞百分比减低者1例（25%）;IgG升高者1例（25%）,IgM下降者2例（50%）,IgA下降者1例（25%）,4例患儿IgE均升高（100%）。13例患儿共发现13种14个基因突变,其中错义突变9例（65%）,剪接突变2例（14%）,无义突变2例（14%）,移码突变1例（7%）。随访39（3~62）个月,13例患儿均存活。结论 Wiskott-Aldrich综合征发病年龄小,男性为主,主要临床特征为血小板减少伴血小板体积缩小,基因突变以错义突变为主。     

THE INCIDENCE OF DIABETES MELLITUS IN SWEDISH CHILDREN 0–14 YEARS OF AGE

ABSTRACT. This is a prospective study of the incidence of insulin-dependent diabetes mellitus (IDDM) in children 0–14 years of age, including all newly diagnosed cases in the whole of Sweden from July 1, 1977 until June 90, 1980. All 45 Swedish departments of paediatrics participated. During the three-year-period studied, 1108 Swedish children, 0–14 years of age had their onset of diabetes. That means around 369 new diabetics yearly in the age groups studied. The mean yearly incidences in the years 1977–80 were 22.6, 22.8 and 22.6 per 100000 children, respectively. Mean prevalence on June 30, 1980 was 1.48 per 1000 children 0–14 years with a wide range of 0.71-2.65. The age distribution at onset showed a gradual increase and peak incidences at 11 years of age for the girls and 4 and 13 years of age for the boys. There was a consistently higher incidence for boys in the younger age groups during the three-year-period studied. Peak incidences of new cases were reached in January, March and July through October for the age groups 5–9 and 10–14 years of age. No such seasonal variation was seen for children 0–4 years of age. The cumulative incidence of IDDM at 14 years of age was 3.2 per 1000 for the boys and 2.9 per 1000 for the girls. The degree of ascertainment in this study was 93.4 %.     

96例小儿颞骨骨折的临床特点和处置体会

目的：探讨小儿颞骨骨折的临床特点和处置方法。方法：通过回顾性分析1988～2002年间所收治的96例109侧小儿颞骨骨折的临床资料(其中13例为双侧颞骨骨折)。96例患儿，发病年龄在3个月～14岁，平均8．9岁；(男66例，女30例，男女之比为2．2：1)。交通事故伤52例(54．17％)，打击伤18例(18．75％)，坠落伤14例(14．58％)，跌伤12例(12．5％)。纵向骨折41例(37．6％)，横向骨折17例(15．6％)，斜形骨折15例(13．8％)，凹陷性骨折12例(11．0％)，混合性骨折24例(22．0％)；其中，骨折线向颅底延伸65例(59．6％)。骨折合并耳道出血49例(45．0％)、脑脊液耳漏22例(20．2％)、脑脊液鼻漏17例(15．6％)、听力障碍50例(45．9％)、面神经麻痹13例(11．9％)、脑膜炎2例(1．8％)。并发硬膜外血肿20例(18．3％)，硬膜下血肿27例(24．8％)，骨折造成的脑挫裂伤35例(32．1％)，单纯蛛网膜下腔出血41例(37．6％)，颅内积气36例(33．0％)。结果脑脊液耳漏和脑脊液鼻漏经保守治疗均痊愈，听力障碍50例中，28例完全恢复(56．0％)，15例部分恢复(30．0％)，7例完全性失聪(14．0％)。13例面神经损伤患儿中，10例6个月内完全恢复，2例1年后完全恢复，1例部分恢复。结论：小儿颞骨骨折多发生于交通事故、打击、坠落、跌伤，面神经损伤发生率较小，且恢复良好。听力损害恢复较差。及时治疗可提高并发症的治愈率。     

Fetal alcohol syndrome: a prospective national surveillance study.

OBJECTIVE: To describe the epidemiology of cases of fetal alcohol syndrome (FAS) seen by Australian paediatricians. METHODS: Active, national case-finding using the Australian Paediatric Surveillance Unit (APSU). Monthly reporting of incident cases aged <15 years by paediatricians between January 2001 and December 2004. RESULTS: Over 1150 paediatricians submitted reports each month to the APSU. Of 169 reported cases, 92 fulfilled the study criteria for FAS. There was a significant increase in the number of children reported each year from 2001 to 2004. Of 92 children, 53.3% were male, 35.7% were preterm (<37 weeks' gestation) and 64.6% were of low birth weight (<2.5 kg). Most (94.4%) had high risk exposure to alcohol in utero and 78.3% were exposed to one or more additional drugs. The median age at diagnosis was 3.3 years (range: newborn to 11.9 years): 6.5% were diagnosed at birth and 63% by 5 years of age. Of the 92 cases, 56% had growth deficiency, 53.2% had microcephaly, 85.9% had evidence of central nervous system dysfunction, 24% had additional birth defects, 5.4% had sensorineural deafness and 4.3% had visual impairment. Of children with FAS, 65% were Indigenous, 51% had a sibling with FAS, and only 40.2% lived with a biological parent. CONCLUSION: Our data are the only prospective national data available on FAS throughout the world. These findings highlight the severity, complexity and impact of FAS, the need for effective strategies for prevention, and the necessity for education to facilitate earlier diagnosis, referral and reporting of cases.     

Outcome in infants of birth weight 500 to 999 g: a continuing regional study of 5-year-old survivors

During 1979 and 1980, 351 infants of birth weight 500 to 999 g were born in the State of Victoria: 89 (25.4%) survived to the age of 2 years corrected for prematurity, and 83 were fully assessed by a multidisciplinary team; partial data were obtained on the remainder. At the age of 5 years, corrected for prematurity, 85/89 (96%) were evaluated by a multidisciplinary team, although not all children could be fully evaluated by the psychologists. Reports were available for another three children; one child was untraced. Of the survivors able to be classified at 5 years, 59/82 (72%) had no functional handicap. Functional handicaps was severe in 16 (19%), moderate in four (5%), and mild in three (4%). Functional handicaps were present in 50% (8/16) of outborn survivors compared with the 23% (15/66) for the inborn survivors (P = 0.02). Cerebral palsy was diagnosed in eight children at 5 years and in 12 children at 2 years. The diagnosis was stable for the children not ambulant at 2 years; five of seven 2-year-old children with mild cerebral palsy had "outgrown" the diagnosis by 5 years, but ataxic cerebral palsy was not identified in one child until 5 years. Six children were blind; four had severe sensorineural or mixed deafness, one more than at 2 years. Of 82 children assessed according to identical criteria for functional handicap at both 2 and 5 years, 52 (63%) remained in the same category at 5 years, three (4%) were judged to be more severely handicapped, and 27 (33%) were less severely handicapped. The 2-year evaluation of extremely low birth weight children often proved to be unduly pessimistic, for many showed improvement or recovery from functional handicaps and impairments by 5 years of age.     

Myasthenia gravis in childhood

Clinical features, serum acetylcholine receptor antibody (AChRAb) titres and course were reviewed in a series of 25 congenital (CMG) and 30 juvenile (JMG) myasthenia gravis cases to recognize characteristics of childhood-onset myasthenia and its subgroups. The initial symptom for CMG is ptosis accompanied or followed by generalized weakness; myasthenic crises do not occur and spontaneous remissions are rare. In JMG, the distribution of weakness remains the same, but the severity fluctuates: spontaneous remissions (6 patients) and myasthenic crises (10 patients) are observed. Good response to anticholinesterase drugs is slightly more frequent in JMG (62 versus 41 %). AChRAbs were present in 9/26 JMG tested, girls with onset after 11 years being more likely to be Ab-positive. Since patients with autoimmune myasthenia and a young age of onset are often seronegative, clinical features such as changing distribution of weakness, fluctuating severity, or response to treatment might be considered as supportive criteria for differentiating JMG from CMG.     

Outcome of confirmed symptomatic congenital cytomegalovirus infection.

Sixty five neonates with confirmed symptomatic congenital cytomegalovirus infection were followed up prospectively until they were 3 to 4 year of age. Twenty nine children (45%) had neurological impairment of whom 22 had gross motor or psychomotor abnormalities; in the remaining seven sensorineural deafness was the main abnormality. Infants who had had neurological signs during the neonatal period had a worse prognosis than those who had not, with 16/22 (73%) and 13/43 (30%) having neurological deficit at follow up, respectively. Our results indicate that the prognosis for infants with symptomatic congenital cytomegalovirus infection is better than previously reported.     

111 例未通过听力筛查新生儿常见耳聋基因突变位点分析

目的了解未通过听力筛查新生儿耳聋基因突变情况。方法随机选取听力筛查未通过、经听觉脑干诱发电位(ABR)测试为感音神经性耳聋患儿111例,收集足跟血血片,提取基因组DNA后,检测GJB2、SLC26A4和线粒体12 Sr RNA基因中的11个热点的突变,分析听力损失程度与突变的关联。结果 111例新生儿中,共检出携带耳聋基因突变24例(21.6%)。其中,GJB 2基因突变14例(12.6%),包括235 del C单杂合突变5例,235 del C和299_300 del AT复合杂合突变5例,以及235del C纯合突变、299_300del AT单杂合突变、176_191del16和235del C复合杂合突变、299_300del AT和508_511 dup AACG复合杂合突变各1例;SLC 26 A 4基因突变10例(9.0%),包括IVS 7-2 AG单杂合突变2例,1226 GA单杂合突变3例,2168 AG单杂合突变2例,IVS7-2AG和2168 AG复合杂合突变3例。本组耳聋患儿中未检出线粒体基因突变。结论未通过听力筛查新生儿中,超过1/5检测到聋基因突变,并以GJB2基因突变最常见,实施热点致聋基因检测可以提高耳聋的病因诊断率。     

A case series of Turkish children and adolescents with bipolar spectrum disorder: a naturalistic clinical phenomenological follow-up

AIM: The main objectives of this a naturalistic, prospective follow-up study were to describe the clinical presentation and predictors of treatment response in Turkish children and adolescents with bipolar disorder (BD) and to document their response to available treatment regimes. METHODS: The study sample consisted of 27 consecutive admissions to the Child and Adolescent Psychiatry Clinic between 2002 and 2006. Washington University at St. Louis -Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) was administered to mothers for an assessment of the problem of their children and to children about themselves. Subjects were phenomenologically re-examined to ascertain whether they met the Leibenluft criteria for the narrow, intermediate, or broad phenotypes of juvenile mania. All patients were also rated with Children Global Assessment Scale (CGAS) and Young Mania Rating Scale (YMRS). Treatment response was documented using the Clinical Global Impression (CGI) and the YMRS. RESULTS: The mean age was 12.95+/-3.8 years and the mean follow-up period was 24+/-9.2 months. Nineteen (70.3%) patients continued their treatment for 20.6+/-12.47 months. A large number of patients responded to mood stabilizers and antipsychotic agents (89.5%). When treatment endpoint scores of CGAS were compared between patients with age at onset =or>13 and <13, functionality of group with age at onset =or>13 was significantly greater than early onset group at the end of the treatment(z:-2.014, P=0.044). CONCLUSION: Compared to non-episodic patients, episodic patients were more likely to have psychotic features and to have a later age of onset. Mood stabilizers and atypical antipsychotic combination was required in many cases (73.7%). Long term follow-up clinical phenomenological and treatment efficacy studies are needed in the future.     

糖原贮积病Ⅱ型GAA基因变异特点及基因型与表型的关系

目的:探讨糖原贮积病Ⅱ型患者酸性α-葡萄糖苷酶(GAA)基因变异特点及基因型与表型的关系,并根据健康儿童GAA基因变异携带率推断理论发病率。方法:回顾性分析2010年1月至2020年5月广州市妇女儿童医疗中心确诊的18岁前起病的57例糖原贮积病Ⅱ型患者的临床资料及GAA基因分析结果,采用荧光底物法检测外周血淋巴细胞或干血斑中GAA活性,采用Sanger测序法进行GAA基因变异分析。以2395名健康儿童全外显子测序中GAA基因检测计算GAA基因变异携带率。组间率的比较采用χ2检验。结果:57例患儿中男26例,女31例。婴儿型患者28例,主要表现为进行性全身肌无力及心肌肥厚,发病年龄(2.5±1.4)月龄,确诊年龄(5.0±3.0)月龄,其中26例于1岁内死亡。晚发型患者23例,表现为肌无力、呼吸困难等,发病年龄(12.0±5.0)岁,确诊年龄(17.0±7.5)岁,7例诊断时已出现呼吸衰竭。非典型婴儿型6例,1岁左右发病,表现为肌无力伴肥厚性心肌病,诊断年龄为2.5~7.0岁。GAA基因分析显示,57例患者共检出47种变异,其中3种错义变异c.797C>T、c.1109G>A及c.1757C>T为可能致病新变异。c.1935C>A(25/114,21.9%)和c.2238G>C(15/114,13.2%)为较常见变异,57.1%(16/28)婴儿型患者检出c.1935C>A的纯合或复合杂合变异,65.2%(15/23)晚发型患者携带c.2238G>C。c.796C>T及c.1082C>T多见于非典型婴儿型。在28例婴儿型患者中,26例(92.9%)至少携带1个错义变异。健康儿童GAA基因致病变异携带率为24/2395,推测该病的理论发病率为1/40000。患者组GAA变异谱与健康儿童携带的GAA变异谱基本一致,假性缺陷变异c.1726G>A和c.2065G>A纯合子检出率在患者组分别为26.3%(15/57)和35.1%(20/57),在健康儿童组分别为1.7%(40/2395)和3.9%(94/2395),两组比较差异均有统计学意义(χ2=151.2、121.9,均P<0.01)。结论:糖原贮积病Ⅱ型临床表现呈连续的临床谱特征,少数患者为非典型婴儿型。常见的2种变异c.1935C>A和c.2238G>C分别与婴儿型及晚发型有关,c.796C>T及c.1082C>T多见于非典型婴儿型。绝大多数婴儿型患儿因携带1个错义变异推测为交叉反应性免疫物质阳性。糖原贮积病Ⅱ型理论发病率约1/40000。     

儿童肝豆状核变性临床表型及ATP7B基因突变关联性分析

目的 了解汉族儿童肝豆状核变性(WD) 患儿的临床表型与ATP7B基因突变的相关性。方法 以2005年7月至2012年12月就诊于复旦大学附属儿科医院确诊WD患儿为研究对象,按起病部位分为肝病型和神经型,以临床表现分为临床型和亚临床型。采用PCR技术扩增ATP7B基因全部外显子并直接测序。提取临床表型和基因型的信息;分析两者之间的相关性。结果 52个无亲缘关系家庭的53例WD患儿进行分析。肝脏损害52例（98.5%）。肝病型41例,神经型12例;临床型19例,亚临床型34例。①肝病型ALT升高明显;神经型24 h尿铜水平、胆汁酸水平和K-F环阳性率均显著高于肝病型;亚临床型起病年龄、ALT或AST异常率显著高于临床型;24 h尿铜水平、胆汁酸升高比例和K-F环阳性率显著低于临床型。②53例WD患儿ATP7B基因外显子序列分析发现致病性突变等位基因97个,突变频率为91.5%。纯合突变8例,复合杂合36例,杂合突变9例。错义突变23种,插入/缺失突变8种,无义突变2种,剪接突变3种。③错义突变与非错义突变,纯合突变与杂合突变患儿在起病年龄、K-F环阳性率、铜蓝蛋白水平、24 h 尿铜水平和ALT、AST异常率等方面差异无统计学意义。④3种高发突变p.Arg778Leu（35.0%,34/97）、p.Pro992Leu (15/97,15.5%)和p.Ala874Val/Pro(5/97,5.2%)在临床型和亚临床型、肝病型和神经型间的分布差异无统计学意义。⑤纯合、错义和错义+剪接突变在临床型和亚临床型、肝病型和神经型间的分布差异无统计学意义。结论 WD患儿几乎均有肝脏受累,多以肝病表现起病。ATP7B常见突变为p.Arg778Leu、p.Pro992Leu和p.Ala874Val,常见基因型和临床表型间未发现显著相关性。p.Ala874Val/Pro突变患儿起病年龄较低,剪接突变对血清铜蓝蛋白影响较小。