15 years of national screening for phenylketonuria in The Netherlands; 4th Report of the National Commission for Management of Phenylketonuria

In the period 1st September 1974 to 1st January 1989 2,511,000 infants (99.3% of all livebirths) were screened for PKU. Treatment was required in 158 of the 330 referred infants. The diagnosis of these 158 patients was PKU (137), hyperphenylalaninaemia (HPA) (19) and malignant HPA (2). Three cases had a false-negative screening result. The prevalence of PKU, treated HPA and malignant HPA in the Netherlands is 1:18,000, 1:132,000 en 1:1,300,000. Height adjusted for age was in 24% of the patients with PKU of Dutch parents and weight adjusted for height in 11% under the 10th centile. Ninety per cent of the patients with PKU of 5 years and older attended primary or secondary school, compared with 95% in the general population.     

山东省高苯丙氨酸血症分型及治疗效果评价与基因分析

【目的】 了解本省高苯丙氨酸血症(hyperphenylalaninemia,HPA)的分型、不同类型治疗效果、影响因素及四氢生物蝶呤缺乏症(tetrahydrobiopterin deficiency,BH4D)基因分析情况。 【方法】 对在济南市新生儿疾病筛查中心确诊的396例HPA患儿根据BH4负荷试验及尿蝶呤谱分析结果判断患儿的临床分型(苯丙氨酸羟化酶缺乏症及BH4D)。根据不同类型对症治疗,并定期监测血苯丙氨酸浓度及生长发育评价,对BH4D患儿进行基因分析。 【结果】396例HPA患儿中356例为苯丙氨酸羟化酶缺乏,40例BH4D,128例BH4反应性苯丙氨酸羟化酶缺乏症。155例随访患儿,末次随访6月~15岁,平均年龄6.5岁。治疗后HPA患儿体格发育与同年龄组正常儿童相比差异无统计学意义。155例HPA患儿智商正常132例(占85.2%)。经典型PKU患儿智商与血Phe浓度相关分析显示二者呈负相关(r=0.416,P<0.01)。BH4D患儿智商水平与开始治疗时有无神经系统症状密切相关。11例BH4D携带6种基因突变,259C>T占42.1%。 【结论】 不同临床表型和生化表型的HPA患儿经早期诊断治疗体格发均在正常范围,85%的患儿智力正常。经典型PKU患儿智力发育水平与血Phe浓度负相关,浓度的升高或波动较大均能严重影响患儿智力水平。BH4D患儿治疗效果与开始治疗的时间密切相关。本地区BH4D患儿较为集中的基因突变位点是259C>T。     

四氢生物喋呤负荷试验在高苯丙氨酸血症鉴别诊断中的临床应用

目的探讨四氢生物喋呤（BH4）负荷试验在高苯丙氨酸血症（HPA）鉴别诊断中的应用价值。方法自2008年1月-2010年6月,27例HPA患儿采用口服BH4（20 mg/kg）负荷试验。对其中血苯丙氨酸（Phe）浓度小于6 mg/dl患儿采用口服Phe-BH4联合负荷试验,结合尿喋呤分析、血红细胞二氢喋呤还原酶（DHPR）活性测定。结果 （1）在BH4负荷试验中,不同类型HPA患儿的血Phe浓度表现出各不相同的改变。27例HPA患儿中,共鉴别出5例BH4缺乏症,9例BH4反应性苯丙氨酸羟化酶（PAH）缺乏症,13例BH4无反应性苯丙氨酸羟化酶（PAH）缺乏症。（2）在22例中度苯丙酮尿症（PKU）患儿中,9例为BH4反应性PAH缺乏症。结论 BH4负荷试验在HPA早期鉴别诊断中十分重要,部分中度PKU对BH4有反应,可使用BH4替代治疗。     

武汉市新生儿苯丙酮尿症筛查11年分析研究

目的:回顾武汉市新生儿苯丙酮尿症11年筛查情况,总结经验、查找不足,促进筛查工作。方法:新生儿出生后72h,采足跟末梢血制成滤纸干血片,检测血片中Phe含量,将Phe值≥240μmol/L(BIA法)或≥120μmol/L(荧光法)的新生儿判为初筛阳性,召回复查确诊。结果:11年来,武汉市筛查新生儿321881例,确诊PKU患儿15例,PKU发病率为0.47/万;PKU发病率无显著上升或下降趋势;用BIA法筛出的PKU发病率与用荧光法筛出的发病率无显著差异。结论:武汉市PKU发病率处于相对稳定的较低水平,用荧光法筛查要优于BIA法,新筛实验室应尽可能使用荧光法,既可降低初筛阳性率,又能提高检出率。要提高筛查覆盖率,加强PKU与BH4的鉴别诊断,研究武汉市PKU患儿家族苯丙氨酸羟化酶基因突变情况,为PKU的产前诊断提供依据。     

Growth parameters in newborns with hyperphenylalaninaemia

To understand the effects of hyperphenylalaninaemia on fetal growth, we studied growth parameters (weight, length and head circumference) of 23 phenylketonuric (PKU) and 60 hyperphenylalaninaemic (HPA) newborns from healthy mothers and of 1853 healthy neonates from north-east Italy. A comparison of the growth parameters for both PKU and HPA newborns, as well as for controls, showed a statistically significant higher percentage of PKU and HPA patients with reduced body length and cranial circumference (P < 0.05 for both parameters in affected neonates). The z-scores for all growth parameters regarding both PKU and HPA newborns and controls, and between PKU and HPA newborns according to the Mann-Whitney non-parametric test, were statistically significantly lower in PKU newborns than in controls; in contrast, only body length was significantly lower in HPA newborns than in controls (P < 0.01). A comparison of growth parameter z-scores using the Kruskal-Wallis test for PKU, HPA and control newborns showed that both body length (P < 0.01) and cranial circumference (P < 0.05) were significantly lower in both groups of affected neonates. Our results showed intrauterine growth retardation for both PKU and HPA newborns. Body length and cranial circumference appeared to be more important than birthweight in evaluating growth of PKU and HPA newborns.     

2010-2016年陕西省新生儿疾病筛查治疗及随访结果分析

目的 总结并分析2010-2016年陕西省新生儿疾病筛查中心高苯丙氨酸血症(HPA)、先天性甲状腺功能减低症(CH)的筛查及治疗、随访情况。方法 新生儿出生72 h后采集足跟血,制成干血滤纸片,采用荧光法检测滤纸干血斑中苯丙氨酸(Phe)、促甲状腺素(TSH)的水平,Phe ≥2.0 mg/dl、TSH ≥10 μU/ml为阳性,阳性病人召回复查,采用串联质谱法检测血Phe、酪氨酸(Tyr),化学发光免疫分析技术检测甲状腺功能五项(TSH、T₃、T₄、FT₃、FT₄)而确诊。结果 2010-2016年全省助产机构活产数共2 751 268例,接受筛查2 329 335例,筛查率84.67%;确诊轻度HPA 131例,发病率1/17 781;确诊苯丙酮尿症(PKU) 300例,发病率1/7 764; 确诊CH 966例,发病率1/2 411。确诊后即建立病历档案,分别给予低苯丙氨酸饮食及口服左旋甲状腺素片(L-T₄)替代治疗。通过Gesell发育量表监测发育情况,发现6月龄内开始接受治疗的PKU患儿智商(IQ)水平明显优于6月龄后开始治疗的患儿(P<0.01),筛查确诊后即坚持治疗随访的CH 患儿,其IQ与正常同龄儿无明显差异(P>0.05)。结论 全面开展新生儿疾病筛查,提高筛查覆盖率,尽早规范化开始治疗及长期随访监测,可使PKU、CH患儿避免体格和智力不可逆损害,对改善其预后和生存质量意义重大。     

高苯丙氨酸血症1 066例随访分析

【目的】 了解高苯丙氨酸血症(hyperphenylalaminemia, HPA)患者治疗随访及预后。 【方法】 对在本院诊断治疗的1 066例HPA的治疗随访结果进行回顾性分析。 【结果】 1)在1 066例HPA患儿中,共有1 016例为苯丙氨酸羟化酶缺乏症,即经典型苯丙酮尿症(phenylketonuria, PKU),50例为四氢生物蝶呤缺乏症(tetrahydrobiopterin deficiency, BH₄D)。在这些PKU患者中,有369例(34.62%)患儿在新生儿筛查时被确诊并在3个月内开始规律治疗,241例(22.61%)在生后3～12个月内确诊, 456例(42.78%)在1岁后才确诊。2)3个月内筛查治疗的患儿智力发育明显高于非筛查确诊的患儿(96±15, 69±11;t=14.19,P＜0.01﹚。3)3个月后才确诊的经治疗后智力水平也有明显提高﹙46±15,69±11,t=7.13,P＜0.05﹚。4)氢质子磁共振波谱(¹HMRS)检测22例HPA患儿的脑苯丙氨酸(phenylalanine, Phe)浓度表明患儿血、脑Phe浓度与智商均呈负相关关系(r_血=0.505,r_脑=0.647,P<0.01)。 【结论】 对所有HPA患者均应进行鉴别诊断,尽早确诊和治疗, 控制血、脑苯丙氨酸浓度是减少智能落后的有效措施。     

连云港市新生儿筛查疾病的临床流行病学研究

目的研究连云港地区新生儿筛查疾病——先天性甲状腺功能减退症（CH）和苯丙酮尿症（PKU）的临床流行病学特征。方法对2000年9月—2005年8月出生的共139604名新生儿，采集其出生72h后的足跟血于干血滤纸片上。采用测血苯丙氨酸（Phe）作为PKU的筛查指标，用盖氏细菌抑制法测定：采用促甲状腺素（TSH）作为CH的筛查指标，用酶联免疫吸附试验（ELISA）或时间分辨荧光免疫法（TRFIA）。结果确诊CH病儿58例，发病率41.54／10万（1／2407）；经甲状腺核素显像40例，其中甲状腺异常22例（55％）；临床流行病学调查58例病儿分布在全市的4县3个城区的43个乡镇（街道），男女性别无差异，农村发病率高于城区（P〈0．05），发现1对双胞胎CH病儿；确诊苯丙酮尿症病儿15例，发病率为10．74／10万（1／9307）；以上病儿父母未见近亲结婚和显性遗传家族史，母孕期正常，经干预治疗。病儿身体与智力发育与同龄儿比较无明显差异。结论CH、PKU在连云港地区呈散发性分布，发病率属国内平均水平，进行新生儿筛查是发现CH、PKU的唯一有效手段，使病儿得到早诊治，是提高我国人口素质的重要手段。     

惠州市新生儿PKU、CH、G6PD缺陷筛查结果分析

目的:了解惠州市新生儿PKU、CH、G6PD缺陷的发病率及新生儿疾病筛查的情况。方法:对惠州市2004年度新生儿筛查资料及惠州市各区人口出生情况进行回顾性分析。结果:CH的发病率是4/3157,G6PD缺陷的发病率是415/12629,PKU的检出率是1/12629;惠州市的新生儿总筛查率是27.60%。结论:新生儿筛查是早期发现PKU、CH、G6PD缺陷患儿,使其得到早期诊治,避免发生体格和智能发育障碍的有效手段,是提高人口素质的重要措施。     

Antioxidant and thyroid hormone status in selenium-deficient phenylketonuric and hyperphenylalaninemic patients

BACKGROUND: Subjects consuming protein-restricted diets, such as patients with phenylketonuria (PKU) or milder hyperphenylalaninemias (HPAs) are at risk of selenium deficiency. Selenium is a cofactor of the antioxidant enzyme glutathione peroxidase and of the thyroid hormone converting enzyme thyroxine deiodinase. OBJECTIVE: Our goal was to investigate the effects of low plasma selenium on antioxidant and thyroid hormone status. DESIGN: We assessed plasma selenium, plasma total antioxidant status and the individual components thereof, erythrocyte antioxidant status, and plasma thyroid hormones in 24 PKU and 10 HPA patients and in 42 age-matched control subjects. RESULTS: Selenium was significantly lower in both PKU and HPA patients than in control subjects and the PKU patients had lower values than did the HPA patients. Total antioxidant status was lower in both patient groups than in the control group, whereas alpha-tocopherol, albumin, and uric acid were not significantly different among groups. Plasma selenium correlated well (r = 0.76) with erythrocyte glutathione peroxidase. PKU patients had lower glutathione peroxidase activity than did HPA patients and control subjects and lower glutathione concentrations than did control subjects. Both patient groups had lower superoxide dismutase activity than did control subjects. Free triiodothyronine was higher in both patient groups than in control subjects, whereas free thyroxine was higher in the PKU patients only. Free thyroxine and reverse triiodothyronine were inversely correlated with selenium. CONCLUSION: Supplementation with selenium seems to be advisable for patients consuming diets low in natural protein.     

南京市学龄前儿童发育性眼动评估本土化常模的研究

目的 建立南京市学龄前儿童发育性眼动评估本土化常模，为阅读障碍的早期筛查、诊断和干预提供帮助。方法 本研究通过分层随机抽样的方法，利用发育性眼动评估工具对南京市区8所幼儿园的375名5~6岁学龄前儿童进行调查。结果 1)样本的代表性:抽样方法、样本量、样本的基本特征以及数据的收集方式都符合常模建立的要求;2)眼动评估各项结果经统计分析显示，每个年龄段男女之间差异无统计学意义;3)纵向时间、横向时间、纵横时间比、总错误数随着年龄的增长呈逐渐下降或减少的趋势;4)具有良好的效度和信度。结论 眼动评估各指标有显著的年龄梯度，符合正常眼动的发育规律，可作为南京市5~6岁组儿童眼动指标常模。     

Physical functioning and mental health in patients with chronic medical conditions

There is evidence to suggest that a decline in physical functioning with advancing age is independent of mental health, which appears to remain relatively stable. There is additional evidence to suggest that those with a chronic disease also experience a decline in physical function while the mental health remains relatively stable. Using a cross-sectional design, data from the US population norms for the Medical Outcomes Study SF-36 are examined and compared to SF-36 data collected for four patient groups. Patient groups include kidney dialysis patients, multiple sclerosis patients, kidney transplant patients and patients with severe osteoarthritis of the hip prior to total hip replacement. Overall scores and scores within 10-year age groupings are examined in order to compare the physical functioning and mental health scores of the general population with those of the four patient groups. Results support the hypothesis that physical functioning declines with advancing age and with the development of chronic disease, but mental health remains remarkably stable regardless of chronic disease and/or advancing age. This observation suggests a process of psychological adjustment or adaptation to the physical difficulties encountered with advanced age or disability, and implies that this adjustment process may in fact be quite strong.     

EQ-5D-3L Norms for the European Older Population: Country-Specific Norms for 15 European Countires Based on the Survey of Health,Ageing, and Retirement in Europe

ObjectivesThis study presents a country-specific 3-level version of EQ-5D population norms for the European older population.MethodsNorm data were obtained from the fourth wave of the Survey of Health, Ageing and Retirement in Europe, and determined, for each EQ-5D dimension, the EQ–visual analog scale (EQ-VAS) and EQ-5D index values by 7 age groups and sex for 15 European countries. The EQ-5D index values were calculated using the European VAS value set for all countries.ResultsData resulting from 50 013 older respondents (mean age 65.9 years, range 50-111 years, 55.6% women) revealed an increasing number of self-reported health problems on EQ-5D dimensions and decreasing EQ-VAS scores with increasing age and for women compared with men. There are notable differences between countries in terms of the age gradient, the proportion of respondents in full health, and sex. Across all age groups, problems with pain & discomfort are the most frequent (36%-73% any problems), whereas problems with self-care are the least frequent (3%-31% any problems). The mean EQ-VAS score is 71.2 and the mean European VAS score is 0.79.ConclusionsGiven the growing number of older adults and elderly people in Europe, these population norms provide a valuable source of reference data that can be used to compare older adults or patient subgroups to the average of the general elderly population in a similar age or sex group in 15 European countries. The index value results may be further used to assess the burden of disease across older European populations and to identify the unmet needs of targeted older patient populations.     

新生儿苯丙酮尿症综合干预效果的初步评价

评价新生儿苯丙酮尿症(PKU)综合干预的效果,减少PKU患儿生后智力残疾的发生率,提高人口素质。方法:应用Guthrie细菌抑制法进行大样本初筛,对血苯丙氨酸(Phe)浓度高于2mg/dl者复采血片应用该法确诊病例;对确诊病例给以低苯丙氨酸饮食长期治疗,进行定期化验血液Phe浓度及体格检查和智力测试,对家长进行饮食治疗指导,根据化验结果随时调整饮食谱。同时给予免费保偿诊治6年。结果:1999年6月～2004年4月筛查284373例新生儿,确诊PKU41例,其中经典PKU32例,中度高Phe血症5例,四氢生物喋呤缺乏症(BH4D)4例。除了4例BH4D应用药物治疗外,对其他37例患儿采取了综合干预措施,治疗效果良好,体格及智力发育正常率97.30%。社会效益良好,家庭负担明显减轻。结论:对新生儿疾病筛查出的PKU患儿采取综合干预的方法使PKU患儿诊治率明显提高,治疗效果显著,有良好的社会、经济效益,并提高了出生人口素质。而新生儿疾病筛查实行保偿制度是保证综合干预效果良好的关键。     

新生儿苯丙酮尿症筛查结果分析

目的:了解中山地区苯丙酮尿症的发病率、临床类型以及治疗情况。方法:取出生72h后并喂足高蛋白奶6次以上的95471例新生儿足跟血,应用荧光定量法测定血苯氨酸(phe)水平,对PKU患儿给予低phe饮食。结果:在95471例新生儿中检出phe增高(phe≥2mg/dl)的可疑者15例,经血清氨基酸分析,确诊PKU患儿2例,均为经典型PKU,总发病率为1/47736。PKU患儿经治疗后智力明显提高,临床各项指标恢复正常。结论:中山地区PKU发病率低于全国平均水平,对PKU采用的治疗方法适用、有效。     

Normative scores for the Timed Up & Go in a Spanish sample of community-dweller adults with preserved functionality

Our aim was to calculate the ‘Timed Up & Go’ (TUG) normative scores in a Spanish sample composed of functional older adults. The TUG test provides a measure of global ambulation skills and its total score has been successfully related with functionality and other important health variables in older adults. Reliable norms are needed for adults 50 years and older that allow the early identification and intervention in motor disturbances. The study was carried out with adults from Galicia and Valencia living in the community. A total of 314 Spanish community-living participants, aged from 50 to 90 years and functionality preserved were assessed through the implementation of a cross-sectional design. Health, comorbidity, physical activity, cognitive status, functionality measures and TUG test scores were obtained. TUG scores were successfully predicted by age and gender, and significantly correlated with cognitive status and comorbidity. TUG norms were calculated by age-group for women and men. TUG normative scores were below 13 s and slightly lower in men. Normative scores for women and men were lower than those proposed in studies carried-out in our context. Our norms showed risk reference scores close to those obtained by meta-analytical procedures.     

北京市苯丙酮尿症新生儿筛查状况分析

目的 分析和总结北京市苯丙酮尿新生儿筛查状况.方法婴儿出生喂奶72小时后采取足跟血,滴渗在规定的滤纸片上.采用Guthrie细菌抑制法测定血苯丙氨酸含量.结果 北京市自1993年开展苯酮尿症新生儿筛查,筛查率逐年提高,截止到1997年8月达 89.1%.几年来共筛查250 227名新生儿,确诊苯丙酮尿症患儿24名,检出率1:11 705.24名患儿中有17名积极配合治疗智能发育正常、有4名出现不同程度智力异常、另有3名放弃治疗.结论 新生儿筛查能使苯丙酮尿症患儿得到早期诊断和治疗,防止智力低下的发生,     

Validity of the cognitive screening tests and the mini-mental status examination in a group of elderly hospital patients

OBJECTIVE. To study the validity of the cognitive screening test (CST) and of the mini-mental state examination (MMS). DESIGN. Prospective administration of both CST and MMS (in balanced order) by laymen as well as by experienced users, and retrospective comparison of the scores with the clinical diagnosis and with the degree of functioning in activities of everyday life. SETTING. Clinical and outpatient departments of Geriatrics and Neurology of the Slotervaart Hospital, Amsterdam. PATIENTS AND METHOD. Ninety-five patients of the clinical and nine patients of the outpatient departments, with an acute somatic diagnostic problem and multiple pathology attending the above-named departments in the period from September 1989 to February 1990: 20 patients (group SOM) were found not to have a dementia syndrome; 25 patients (group DEM) had a dementia syndrome as the main diagnosis; 14 patients (group CVA) had a cerebrovascular accident as the main diagnosis without clinical signs of dementia; 45 patients were excluded from the comparison (30 because of main diagnosis from several groups and 15 because of pathology that might influence the test scores to an unpredictable degree). The data were analysed statistically by means of analyses of confidence and of variance. RESULTS. The CST was found to be more reliable and less time-consuming than the MMS. The sensitivities of the two tests with regard to the distinction between dementia and somatic pathology were similar (80%). However, specificity of the CST was better than that of the MMS (80% and 60%, respectively). CONCLUSION. For the screening of older patients for dementia, the CST constitutes a good alternative to the MMS.     

张掖市2010—2016年 新生儿代谢性疾病筛查和防治现状分析

目的 探讨张掖市2010—2016年新生儿代谢性疾病筛查和防治现状。方法 依据卫生部《新生儿疾病筛查技术规范》对张掖市妇幼保健院2010年9月30日—2016年10月1日产科新生儿实施疾病筛查,主要筛查项目为苯丙酮尿症（phenylketonuria,PKU)和先天性甲状腺功能减低症（congenital,hypothyroidism,CH）浓度。结果 本次研究共筛选79249例新生儿参与IMD疾病筛查,PHE阳性率为1.60％、复查率为78.91％;CH阳性率为0.49％、复查率为69.15％;79249例新生儿经过筛查确诊PKU 28例,确诊率：28/49249;确诊CH 15例,确诊率：15/49249。28列PKU确诊患儿中,经鉴别诊断确诊1例BH4缺乏症。确诊的28列PKU患儿在筛查中心接受治疗,治疗率96.15%。14例CH患儿得到较好的治疗,1例放弃治疗,其余2例患儿在随访中。GROWTH儿童体格发育测评：1例-2s,3例 -(1S~2S),9例+1S,13例+(1S~2S),2例+2S,无+2S以上患儿。经NDP儿童神经心理发育评价,发现1例中上智能、18例中等智能、5例中下智能、2例低智能。结论 通过筛查得出张掖市2010年-2016年新生儿代谢性疾病筛查具体情况,为疾病防治措施的制定提供科学的依据。     

SF‐6D POPULATION NORMS

The derivation of population norms using simple generic health‐related quality of life measures to inform policy has been recommended in the literature. This letter illustrates the derivation of population norms for the SF‐6D in the United Kingdom. It uses a sample of 22,166 respondents from the 2010 wave of the study Understanding Society. Understanding Society is a national representative sample of British citizens. The survey of this study contains the SF‐12. It is possible to derive health state utilities from the SF‐12 (and from the SF‐36) using a relatively new instrument, the SF‐6D. The SF‐12 and the SF‐36 belong to the most widely used generic health‐related quality of life measures. Mean SF‐6D utility scores for males and females are 0.81 and 0.79, respectively. Especially the older age categories have lower utility scores. The younger age categories have slightly higher utility scores. From a list of 17 conditions, people with congestive heart failure had the lowest (0.60) and people with diabetes the highest (0.76) SF‐6D scores. This letter encourages the health economics research community to derive SF‐6D population norms to inform policy. Copyright © 2012 John Wiley & Sons, Ltd.