儿童矮小症应用生长激素的长期安全性

生长激素(GH)于1956年首先从人垂体中分离出,其生物化学结构直到1972年才阐明.重组DNA技术和基因工程方法,实现了人生长激素(hGH)的大规模生产,使hGH普遍利用成为可能.文章综述生长激素在儿童生长激素缺乏症、慢性肾功能不全、Turner综合征、Prader-Willi综合征、小于胎龄儿持续矮小、特发性矮小、矮小同源异型盒基因(SHOX)缺陷疾病中的应用方法和安全性.提示重组hGH用于儿童的安全性令人满意,但也需注意有潜在风险的特殊群体.     

186例矮小症患者遗传学检测结果分析

目的 探讨儿童矮小症的遗传学病因。方法 选取2017年1月—2020年10月因生长缓慢就诊的矮小症患儿为研究对象。行矮小相关基因的全外显子测序,对发现的可能的染色体片段拷贝数变异者进一步完善基因芯片检查,比较基因检测阳性与阴性组之间临床表型差异。结果 共纳入186例矮小症患儿,中位年龄7.3(5.1～9.1)岁,男103例、女83例。共检测出69例阳性结果,阳性检出率37.1%。其中54例通过全外显子基因测序诊断,15例通过染色体微阵列分析诊断。二元logistic回归分析显示,特殊面容和骨骼发育异常是儿童矮小症基因检测结果阳性发生的预测因素(P均<0.05)。结论 全外显子测序是检测儿童矮小症遗传病因的有效技术手段,伴有特殊面容和/或骨骼发育异常的患儿更可能检测到遗传病因。     

中文版儿童生活功能评估量表重庆地区常模的建立及应用

目的 建立重庆地区中文版儿童生活功能量表（PEDI）的常模。方法 引进英文版PEDI 量表,将量表翻译成中文并经回译校正。在重庆地区按年龄分层抽取1140 名普通儿童,用中文版PEDI 量表进行测评,将所得数据进行统计处理。结果 1140 份问卷中1 075 份为有效问卷,有效应答率为94.3％。测评结果表明不同年龄段儿童的PEDI 量表粗分及刻度分随着年龄的增长而增长,而标准分随年龄增长无太大变化,其中部分年龄阶段儿童自理能力和社会技能项目的粗分、刻度分及标准分均低于美国原版量表参考值（PP>0.05）。结论 成功建立了重庆地区PEDI 常模,可用于评估儿童的生活功能,并作为判断残障儿童生活功能损伤程度,生活功能康复训练效果及制定阶段性康复计划的标准。     

矮小儿童的生长激素-胰岛素样生长因子轴功能的检查

生长激素-胰岛素样生长因子(GH-IGF-1)功能轴的异常是引起儿童身材矮小的重要原因。根据病因可将其分为3类：具有生物活性的生长激素(growth hormone,GH)分泌不足;胰岛素样生长因子(insulin-like growth factors,IGFs)产生减少;外周组织对IGFs产生抵抗。早期明确诊断并应用基因重组人生长激素(rhGH)治疗可以有效地提高最终成人期身高。为了在临床上正确使用rhGH,     

上海市城郊两区整群抽样6～18岁儿童青少年身高分布特点及矮小症患病率调查

目的 研究上海市6~18岁儿童青少年身高及矮小症患病率分布特点。方法 采用整群抽样抽取上海市1个城区和1个郊区,普查2个区内所有6~18岁共70 431名中小学生的身高。分析身高的年龄别分布特点,并与1975、1995年全国和上海市学生体质测试标准进行比较;并以1995年上海市身高评价标准进行评价,分析矮小症患病率分布特点。结果 ①研究人群中身高特点为男性显著高于女性（P<0.000 1）。②男性身高增长以6~15岁较为明显,11岁后身高增长加快,15岁后增幅减小;女性身高增长在6~14岁较为明显,10岁以后增长加快,14岁后增幅减小。③与全国身高标准相比,上海城区和郊区儿童青少年的各年龄组身高均高于全国标准。与1975年上海儿童青少年身高参考标准相比,身高增长分别为城区男性(6.4±2.1) cm,郊区男性(10.5±2.5) cm,城区女性(4.8±0.9) cm,郊区女性(8.6±1.9) cm,其中以郊区儿童青少年特别是11岁以上儿童青少年身高增长更为显著;而城区儿童青少年身高在1995至2003年的增幅较小,在1975至1995年增幅较大。④上海市儿童青少年各年龄组总体矮小症的患病率为0.5%~6.03%,平均患病率为3.77%;城区矮小症的粗患病率为2.78%,标准化患病率为2.57%;郊区矮小症的粗患病率为4.52%,标准化患病率为3.75%。矮小症患病率在13岁以前较高;城区矮小症患病率低于郊区,男、女矮小症患病率在城区相近,在郊区则男性高于女性。结论 上海市儿童青少年身高生长曲线存在性别的三相性差异,6~9岁和12~18岁均呈现男高女低,10~11岁呈现女高男低的特点。1975至2003年上海儿童青少年身高均呈现显著增长现象,但城区儿童身高在1995年后增幅明显减小。上海儿童青少年平均矮小症患病率为3.77%,患病率在13岁以前较高;郊区儿童青少年矮小症患病率高于城区。     

1496例矮小症病因分析及基于IGF-1水平生长激素缺乏症诊断预测模型的建立

目的探讨矮小症患儿的病因及胰岛素样生长因子(IGF)-1与生长激素(growth hormone,GH)水平之间的关系,建立基于IGF-1水平的简易GH缺乏(GHD)诊断预测模型。方法矮小症住院患儿1 496例,采用胰岛素低血糖法和精氨酸法测定GH分泌状态,根据体格检查及实验室检查分析病因;Logistic逐步多元回归模型建立基于IGF-1的GHD诊断预测模型。结果 GHD659例(44.05%),特发性矮小504例(33.69%),家族性矮小165例(11.03%),体质性青春期发育延迟35例(2.33%),余为甲状腺功能减低症、宫内发育迟缓、Turner综合征、多种垂体激素缺乏症等引起的矮小症。比较GHD与非GHD两组患儿潜在的影响因素,体质量、BMI、身高-SDS、ALT/AST/AKP、TG/Tch、IGF-1、IGFBP-3等的差异有统计学意义(P<0.05)。设GHD的概率为P,经Logistic逐步多元回归模型拟合如下:LN[P/(1-P)]=-2.0193+0.0683×年龄+0.1439×BMI+0.021×ALT-0.0021×IGF-1-0.1526×IGFBP-3。结论内分泌疾病是矮小症最多见的病因,但GH激发试验的水平与多种体格和生化指标有关,因此GHD诊断需要综合考虑;基于IGF-1拟合的简易模型对GHD诊断有较准确的预测价值,可用于门诊筛查。     

苯丙酮尿症患者生活质量研究进展

苯丙酮尿症是常见的先天性氨基酸代谢缺陷疾病,其遗传方式为常染色体隐性遗传,已经列入我国新生儿遗传代谢病筛查项目.早期筛查的普及和及时的治疗使得患者躯体症状得以改善,但仍会对远期社会功能以及心理发展产生不同程度的影响.随着医疗模式的改变,以心理和社会功能为主要内容的生活质量研究受到关注.目前国内外学者主要采用普适性量表和特异性量表等评估方法研究苯丙酮尿症对生活质量的影响,大部分研究结果表明早期、及时和长程的治疗有利于提高患者的生活质量水平.该文从苯丙酮尿症患者生活质量的评价方法、影响因素以及研究现状进行综述,对了解苯丙酮尿症患者生活质量现状、指导临床治疗以及判断预后具有重要意义.     

安徽省104例苯丙酮尿症患儿生活质量及其影响因素研究

目的了解苯丙酮尿症(PKU)患儿的生活质量及其影响因素。方法以安徽省三家主要妇幼保健机构诊治的104名PKU患儿为研究对象,采用Peds QLTM 4.0普适性核心量表评价患儿的生活质量。采用多因素logistic回归分析法调查患儿生活质量的影响因素。结果 104名PKU患儿生活质量总评分及其3个维度生理功能、情感功能、社会功能的得分均低于一般在校学龄儿童(P0.01),由情感功能、社会功能和角色功能构成的心理领域得分也低于一般在校学龄儿童(P0.01)。多因素logistic回归分析显示患儿年龄较大(≥4岁)是生活质量的危险因素(OR=8.569,P0.01),监护人就职于企事业单位等是生活质量的保护因素(OR=0.206,P0.05)。结论 PKU患儿生活质量水平较低,影响患儿生活质量的主要因素是患儿年龄和监护人职业。     

原发性免疫性血小板减少症儿童生活质量及其影响因素研究进展

原发性免疫性血小板减少症(primary immune thrombocytopenia,ITP)是儿童最常见的出血性疾病,常表现为皮肤和黏膜出血,罕见颅内出血。儿童ITP为急性自限性疾病,大多数出血倾向重但预后良好;少数迁延反复,呈慢性趋势。尽管儿童ITP严重出血风险低,但慢性ITP血小板计数反复减少常引起家属的担忧,故患儿的日常活动常会受到限制。此外,治疗药物引起的相关不良反应、对病程迁延及疾病预后的担忧等都会影响到患儿的健康及相关生活质量。该文主要针对ITP儿童的生活质量及主要影响因素研究进展展开论述。     

重组人生长激素治疗对特发性矮小症儿童血清Klotho和成纤维细胞生长因子23的影响北大核心CSCD

目的比较重组人生长激素(recombinant human growth hormone,rhGH)治疗前后特发性矮小症(idiopathic short stature,ISS)患儿血清Klotho、成纤维细胞生长因子23(fibroblast growth factor,FGF23)和胰岛素样生长因子(insulin-like growth factor,IGF)-1水平变化,探讨Klotho和FGF23与ISS患儿生长激素(growth hormone,GH)/IGF-1生长轴的关系。方法前瞻性选择2021年3月10日—2022年12月1日在河北省人民医院儿科确诊为ISS的33例儿童为ISS组,选择同期于儿童保健科就诊,年龄、性别与ISS组匹配的29例健康儿童为健康对照组。ISS组给予rhGH治疗,比较治疗前及治疗3、6、9个月血清Klotho、FGF23、IGF-1水平,并进行相关性分析。结果ISS组与健康对照组的血清IGF-1、Klotho、FGF23水平比较差异无统计学意义(P>0.05)。rhGH治疗3、6、9个月的ISS组血清Klotho、FGF23、IGF-1水平均较治疗前显著升高(均P<0.05)。ISS组治疗前Klotho、FGF23与磷酸盐水平均呈正相关(P<0.05);治疗前及治疗3、6、9个月的Klotho与IGF-1水平均呈正相关(P<0.05),FGF23与IGF-1水平均呈正相关(P<0.05),Klotho与FGF23水平均呈正相关(P<0.05),Klotho、FGF23水平与身高标准差积分无相关性(P>0.05)。结论rhGH治疗可上调Klotho、FGF23及IGF-1水平,实现ISS患儿的追赶生长。Klotho、FGF23可能并非直接促进ISS患儿线性生长,而是可能通过IGF-1及磷酸盐代谢等途径产生间接影响。Klotho、FGF23与IGF-1的一致变化表明三者在调节ISS线性生长中存在协同关系。     

儿童身材矮小的病因分析及遗传学诊断

目的 探讨身材矮小患儿的病因分布及遗传学诊断。方法 回顾性分析86例身材矮小患儿的病因分布及临床特征。结果 86例身材矮小患儿中,病因有6种,以特发性矮小症（ISS,41%）和生长激素缺乏症（GHD,29%）最常见,遗传性疾病（14%）次之。将遗传性疾病组与ISS组、GHD组比较显示,各组患儿就诊年龄、身高、出生身长、出生体重、父母身高及胰岛素样生长因子1（IGF-1）水平差异均无统计学意义（P > 0.05）,但遗传性疾病组身高距同年龄同性别个体身高第3百分位数的差值（ΔP3）和身高标准差评分（HtSDS）显著低于ISS组（P < 0.05）,但与GHD组相比差异无统计学意义（P > 0.05）。对遗传性疾病组患儿的临床表现进行分析,显示不同遗传性疾病表型谱存在异质性及表型重叠性。结论 ISS、GHD和遗传性疾病是儿童身材矮小的主要病因。对存在严重身材矮小的患儿,在除外GHD外,有必要进一步行遗传学检查明确诊断。     

Psychometric properties of the Swedish PedsQL, Pediatric Quality of Life Inventory 4.0 generic core scales

Aim:  To study the psychometric performance of the Swedish version of the Pediatric Quality of Life Inventory (PedsQL) 4.0 generic core scales in a general child population in Sweden.
Methods:  PedsQL forms were distributed to 2403 schoolchildren and 888 parents in two different school settings. Reliability and validity was studied for self-reports and proxy reports, full forms and short forms. Confirmatory factor analysis tested the factor structure and multigroup confirmatory factor analysis tested measurement invariance between boys and girls.
Results:  Test-retest reliability was demonstrated for all scales and internal consistency reliability was shown with α value exceeding 0.70 for all scales but one (self-report short form: social functioning). Child-parent agreement was low to moderate. The four-factor structure of the PedsQL and factorial invariance across sex subgroups were confirmed for the self-report forms and for the proxy short form, while model fit indices suggested improvement of several proxy full-form scales.
Conclusion:  The Swedish PedsQL 4.0 generic core scales are a reliable and valid tool for health-related quality of life (HRQoL) assessment in Swedish child populations. The proxy full form, however, should be used with caution. The study also support continued use of the PedsQL as a four-factor model, capable of revealing meaningful HRQoL differences between boys and girls.     

Coeliac disease in children of short stature without gastrointestinal symptoms

Eighty-seven children with short stature (height more than 2 SD below the mean for age and sex) were investigated by small intestinal biopsy. There was no obvious reason for their growth retardation found by routine examination and they had no gastrointestinal symptoms. Coeliac disease was found in two children and probable coeliac disease in two children. Although the prevalence of coeliac disease was comparatively low in this study of Swedish children with short stature, it emphasizes the fact that coeliac disease must be considered in a child with short stature even in the absence of gastrointestinal symptoms.     

Psychosocial assessment of children with short stature: a preliminary report

Previous studies that have examined the psychosocial adjustment of children with short stature have often been flawed, for two main reasons: first, a lack of sample homogeneity and, secondly, the measures of adjustment used have been limited in terms of their sensitivity. This paper examines psychological functioning in the following four broad areas: cognition, social behaviour, emotional adjustment and self-concept. A sample of children referred to growth clinics (mean height below -2 SDS) and a comparison group, recruited from the referred childrens'classes at school, were assessed. Children were prepubertal (age range, 6-11 years) and had no organic cause for their short stature. Parent, teacher and peer reports were used in the assessment, which included sociometric measures in the classroom. The children with short stature described themselves as equally well supported as the comparison children in terms of social support by parents, teachers, peers and friends. Peers reported the short children to be well accepted within their class. Compared with control children, there was a trend for short children to be described by their peers as socially better adjusted than average. Teacher and parental accounts revealed significant group differences in terms of reported behaviour, with poorer attention and more thought problems among the children with short stature. Further analysis suggested, however, that their slightly lower IQ than children of normal height (95.8 ± 18.7 (mean ± SD) compared with 105 ± 15.4) accounted for a greater proportion of the variance in these findings than short stature per se. There is little evidence to indicate that short prepubertal children are psychosocially maladjusted. Their academic performance was poorer than expected on the basis of their cognitive abilities. Reports of immature and impulsive behaviour may not be applicable to a sample of children not referred to a growth clinic.     

特发性矮身材儿童循环microRNA表达水平的研究

目的 研究特发性矮身材（ISS）患儿循环miRNA表达水平,初步建立ISS循环miRNA表达谱,为进一步探索miRNA与ISS发生、发展及寻找新的生物标记物提供理论依据。方法 选取20例ISS患儿和20例健康对照儿童,提取血清总RNA,利用microRNA microarray技术比较ISS患儿与对照儿童血清miRNA的表达差异;实时荧光定量PCR技术验证芯片结果,生物信息学分析软件对筛选出的具有显著差异表达的miRNA进行靶基因预测。结果 ISS组与对照组对比共有40个差异表达的miRNA,其中表达上调的miRNA有24个;表达下调的有16个;实时荧光定量 PCR对其中2个表达上调（miR-185和miR-574-5p）和2个表达下调（miR-497和miR-15a）的miRNA进行验证,ISS患儿血清中miR-185较对照组明显上调（P<0.05）,miR-497明显下调（P<0.05）。结论 ISS患儿与健康对照血清miRNA表达存在显著差异,提示血清miRNA可能与ISS的发生发展有密切的关系。     

儿童短肢型遗传性骨代谢性疾病的临床分析及基因诊断

目的：分析软骨发育不全（ACH）、软骨发育低下（HCH）及假性软骨发育不全（PSACH）3种短肢型遗传性骨代谢性疾病的临床表现、骨骼X线表现及基因结果。方法：对基因确诊的10例短肢型遗传性骨代谢性疾病患儿（其中4例为ACH,3例为HCH,3例为PSACH）的临床特点、骨骼X线表现及基因结果进行分析。结果：10例患儿的平均身高为-3.69±1.79 SD,平均坐高/身高比值为0.65±0.03,平均指间距/身高比值为0.93±0.04。4例ACH患儿及3例PSACH患儿具有典型骨骼X线表现,3例HCH患儿中1例表现为坐骨大切迹变小,1例表现为椎弓根间距未增宽。4例ACH患儿中3例检测到FGFR3基因G380R突变,1例检测到Y278C突变;3例HCH患儿均检测到FGFR3基因N540K突变;3例PSACH患儿检测到COMP基因的杂合突变。结论：ACH及PSACH患儿的矮小程度及骨骼畸形程度较HCH患儿重,HCH患儿临床表现轻,不典型;骨骼X线及基因分析有助于3种疾病的诊断及鉴别诊断;3种疾病涉及2个基因,分别有各自的突变热点,有利于临床基因诊断。     

Measuring quality of life in Japanese children: Development of the Japanese version of PedsQL

Background:  Health-related quality of life (HRQL) is perceived as an important health-care outcome. There are several systems for measuring the HRQL in adults but there are few such systems for children in Japan. Pediatric Quality of Life Inventory (PedsQL) is valid and demonstrates excellent reliability in the USA, Europe, and Asian countries. The aim of the present study was therefore to develop the Japanese version of PedsQL.
Methods:  A two-step procedure was performed: translation of PedsQL, followed by examination of the psychometric properties in a cross-sectional study. The feasibility, reproducibility, internal consistency reliability, factor structure, and concurrent and clinical validity were examined.
Results:  The internal consistency reliability of the Child Self-Reports of young children was slightly low, but that of the Child Self-Reports of school children and adolescents was good. Further, all the Parent Proxy-Reports had excellent alphas. The Japanese version had satisfactory feasibility for all age ranges. The intercorrelation of subscales supported the multidimensional factor structure. Clinical validity was examined by analysis of variance performed for four groups with different health conditions (healthy, chronic needs only, mental condition only, and chronic needs and mental condition). The scores of each functioning scale differed among the four groups, with the healthy group having the highest scores for all functioning scales.
Conclusions:  The Japanese version of PedsQL can be applied in community and school health settings in Japan. Because children with chronic health needs and mental conditions were included, the Japanese version of PedsQL is expected to be useful in clinical settings.     

矮身材女性患儿染色体核型分析及其临床意义

目的　了解女性矮身材与染色体核型之间的关系。方法　对 2 6 1例矮身材的女性患儿常规制备外周血淋巴细胞G显带标本 ,进行染色体核型分析 ,必要时做C带、高分辨G显带分析。根据临床表现将患儿分为两组 :A组为单纯生长落后组 92例 ;B组为疑诊Turner综合征组 16 9例。结果　两组的染色体核型 ,A组 :4 6 ,XX(n =82 ) ;4 5 ,X(n =5 ) ,4 5 ,X/ 4 6 ,XX(n =1) ;4 5 ,X/ 4 6 ,X ,i(Xq) (n =1) ;4 5 ,X/ 4 6 ,X ,mar(n =1) ;4 6 ,X ,del(X) (q12 ) (n =1) ;4 6 ,XX ,t(5 ,11) (5p11p ;5 q11q) (n =1)。B组 :4 6 ,XX(n =75 ) ;4 5 ,X(n =4 8) ;4 6 ,X ,i(Xq) (n =16 ) ;4 5 ,X/ 4 6 ,X ,i(Xq) (n =6 ) ;4 5 ,X/ 4 6 ,X ,mar(n =7) ;4 5 ,X/ 4 6 ,XX(n =2 ) ;4 5 ,X/ 4 6 ,X ,r(X) (n =1) ;4 6 ,XX/ 4 6 ,X ,i(Xq) (n =1) ;4 5 ,X/ 4 6 ,X ,del(X) (q12 ) (n =1) ;4 6 ,XX/ 4 6 ,X ,del(X) (q2 2 q2 4 ) (n =1) ;4 6 ,X ,del(Xp) (n =4 ) ;4 6 ,X ,del(Xq) (n =2 ) ;4 6 ,X ,dir　dup(X) (q2 3→q2 5 ) (n =1) ;4 7,XXX(n =3) ;4 5 ,X/ 4 6 ,XY(n=1)。A、B两组患儿的年龄及染色体核型异常者的年龄比较有显著性差异。结论　①矮身材的女性患儿染色体异常多见 ,故对矮身材的女孩应常规做染色体核型分析 ,以排除染     

Quality of life of young adults with idiopathic short stature: effect of growth hormone treatment

The aim of the study was to evaluate whether treatment with recombinant human growth hormone (rhGH) affects the quality of life of young adults who were diagnosed as idiopathic short stature (ISS) during childhood, and whether their quality of life and aspects of the personality are different from normal. Experiences and expectations concerning rhGH treatment of the subjects and their parents were also investigated. Eighty-nine subjects were included into the study: 24 subjects (16M, 8F) were treated with rhGH from childhood, whereas 65 subjects (40M, 25F) were never treated. At the time of the interview all subjects had attained final height [mean (SD) -2.3 (0.9) SDS for Dutch references], and the age of the treated subjects was 20.5 (1.0)y, and 25.7 (3.5)y of the control subjects (p < 0:001). The level of education was similar, but the treated subjects had less often a partner compared to the control subjects (adjusted for age and gender, p < 0:001). The Nottingham Health Profile and Short Form 36 Health Survey showed no difference in general health state between treated and control subjects, and the healthy Dutch age-specific references (norm group). Although 74% of the subjects reported one or more negative events related to their height, and 61% would like to be taller, only 22% and 11% were willing to trade-off at Time Trade-Off and Standard Gamble, respectively. The personality of the subjects, which was measured by the Minnesota Multiphasic Personality Inventory, was not different from the norm group. The satisfaction with the rhGH treatment was high, as it had caused 12 (8) cm and 13 (7) cm gain in final height according to the subjects and parents, respectively. Based on initial predicted adult height (Bayley & Pinneau), this gain was only 3.3(5.6) cm. We concluded that although the treated subjects had a partner less often when compared to the control subjects, the quality of life of subjects with ISS at adult age is normal and appears not to be affected by rhGH therapy, The treated subjects were very satisfied with the treatment, probably by overestimation of the final height gain.     

人矮小同源盒基因在身材矮小中的研究进展

儿童身材矮小是儿科内分泌常见病,现已证实人矮小同源盒基因(SHOX基因)的缺失和突变是儿童Leri-Weill综合征、Turner综合征及特发性身材矮小和其他具有矮小表型疾病的分子遗传学基础,SHOX基因缺陷的临床表型具有明显的异质性,早期发现SHOX基因的缺陷对矮小症的诊断和治疗具有重要的参考价值和指导意义.