北京市通州区2002至2011年新生儿疾病筛查回顾

目的：分析2002至2011年北京市通州区先天性甲状腺功能减低症（ CH）、苯丙酮尿症（ PKU）的新生儿疾病筛查情况。方法采用回顾性研究的方法,统计分析2002至2011年在通州区各助产机构出生的新生儿先天性甲状腺功能减低症和苯丙酮尿症的数据。结果10年间通州区活产106683人,筛查103531人,随着活产数增加筛查人数逐年增多,平均筛查率为97．05％。全区筛查率呈逐年上升趋势（χ2＝535．748,P＜0．01）。检出先天性甲状腺功能减低症43例,发病率占41．53/10万;检出苯丙酮尿症10例,发病率9．66/10万。10年间可疑病例复查率为83．91％,其中未复查的可疑病例中流动人口占82．80％。结论新生儿疾病筛查是先天性甲状腺功能减低症、苯丙酮尿症三级预防的有效方法,应提高流动人口对新生儿疾病筛查的认识,加强管理,提高新生儿疾病筛查率和复查率。     

Phenotypic variability,neurological outcome and genetics background of 6‐pyruvoyl‐tetrahydropterin synthase deficiency

Leuzzi V, Carducci Ca, Carducci Cl, Pozzessere S, Burlina A, Cerone R, Concolino D, Donati MA, Fiori L, Meli C, Ponzone A, Porta F, Strisciuglio P, Antonozzi I, Blau N. Phenotypic variability, neurological outcome and genetics background of 6‐pyruvoyl‐tetrahydropterin synthase deficiency. This study aimed to investigate the clinical variability and factors implied in the outcome of 6‐pyruvoyl‐tetrahydropterin synthase deficiency (PTPSd). Biochemical and clinical phenotype, treatment variables, and 6‐pyruvoyl‐tetrahydropterin synthase (PTS) genotype, were explored retrospectively in 19 Italian patients (12 males and 7 females, aged 4 months to 33 years). According to the level of biogenic amines in cerebrospinal fluid (CSF) at the diagnosis, the patients were classified as mild (6) (normal level) or severe (13) (abnormal low level) form (MF and SF, respectively). Blood Phe ranged from 151 to 1053 µmol/l in MF (mean ± SD: 698 ± 403) and 342–2120 µmol/l in SF (mean ± SD: 1175 ± 517) (p = 0.063). Patients with MF showed a normal neurological development (a transient dystonia was detected in one), while all SF patients except one presented with severe neurological impairment and only four had a normal neurological development. The outcome of the SF was influenced by the precocity of the treatment. Serial CSF examinations revealed a decline of 5‐hydroxyindolacetic acid in MFs and an incomplete restoration of neurotransmitters in SFs: neither obviously affected the prognosis. PTS gene analysis detected 17 different mutations (seven so far unreported) (only one affected allele was identified in three subjects). A good correlation was found between genotype and clinical and biochemical phenotype. The occurrence of brain neurotransmitter deficiency and its early correction (by the therapy) are the main prognostic factors in PTPSd.     

PKU: high plasma phenylalanine concentrations are associated with increased prevalence of mood swings

In phenylketonuria, knowledge about the relation between behavior and plasma phenylalanine is scarce. The aim of this study was to determine whether high phenylalanine is associated with disturbed behavior noticed by the patient and or close environment (parents or partners). 48 early treated PKU patients (median age 8.5, range 0–35 years) participated (median phenylalanine concentration in total sample 277 (range 89–1171) μmol/l; and in patients < 12 years 238 (range 89–521) μmol/l). After sending blood samples, patients or close environment were interviewed with a standardized questionnaire whether they noticed hyperactivity, annoying behavior, mood swings and introvert or extravert behavior. The interviewer as well as the respondents were blinded with regard to the phenylalanine concentration. Results: Patients reported less deviant behavior compared to close environment. Mood swings were positively associated with phenylalanine concentrations in the total group (P = 0.039) and patients < 12 years (P = 0.042). The relationships between temporary high phenylalanine concentrations and hyperactivity, annoying behavior, introvert and extravert behavior were not statistically significant. Conclusion: there is a positive association between phenylalanine concentrations and mood swings.     

2006年～2010年辽宁省新生儿苯丙酮尿症筛查结果分析

目的分析辽宁省苯丙酮尿症（PKU）筛查情况,提供流行病学基础数据。方法以2005年10月～2010年9月在辽宁省全部新生儿疾病筛查中心进行PKU筛查的139万例新生儿作为分析对象,在出生后72h并充分哺乳后,采足跟血,滴在特定滤纸上,统一寄送筛查中心,进行血苯丙氨酸水平测定,对筛查阳性者进行确诊。结果辽宁省5年来PKU筛查率为88.5%,139万例新生儿中,共确诊PKU217例,PKU检出率为1∶6403,治疗率为90.8%。结论辽宁省近5年PKU的筛查率逐年提高,PKU检出率和治疗率高于全国平均水平。     

Family Social Status and Dietary Adherence of Patients with Phenylketonuria

Objective

There are several problems associated to the management of patients with phenylketonuria (PKU). Social status could be one of the affecting factors on dietary adherence in these patients. The aim of this study was to evaluate family social status and dietary adherence of PKU patients in Iranian population.

Methods

In a cross-sectional study, we studied 105 Iranian PKU patients (born 1984 to 2010), treated and followed at Mofid Children''s Hospital, Tehran. Social status was defined by number of children in family, number of affected children in family, maternal and paternal education, marital and employment status of the parents. Age at diagnosis and duration of treatment were also recorded. Mean plasma phenylalanine level was considered as a sign of dietary adherence in PKU patients and was calculated considering the phenylalanine measurements throughout at least one year.

Findings

Mean plasma phenylalanine concentration was 5.9±3.6 mg/dl in patients <12 years old and 13.1±3.9 mg/dl in patients >12 years old. Blood phenylalanine concentrations in 47.6% of patients were in normal age-related reference range. There was a significant association between divorced and unemployed parents, and higher levels of blood phenylalanine concentration (P=0.02 and P=0.03 respectively). There was a significant positive correlation between number of affected children in the family (r=0.43, P<0.001), age at diagnosis (r=0.2, P=0.03), treatment duration (r=0.7, P=<0.001) and blood phenylalanine concentrations. There was no significant relation between parental education, family size and dietary adherence.

Conclusion

Social status affects dietary adherence to some extent. We suggest exploring care-givers dietary knowledge as the next step to improve dietary compliance in these patients.     

Incidence of phenylketonuria (PKU) in Iran

To find the incidence of PKU in Iran, 8633 neonates from different hospitals in Tehran were screened. Seven of these neonates had minor hyperphenylalaninemia (5 with 6 mg% and 2 with 8 mg%). Only one case with hyperphenylalaninemia (more than 20 mg%) was detected.     

福建省新生儿苯丙酮尿症筛查状况分析

目的：分析和总结1998－2001年福建省新生儿苯丙酮尿症（PKU）筛查状况。方法：新生儿出生后72h采足跟血，滴在规定的滤纸上。采用细菌抑制法（BIA法）或荧光法测定苯丙氨酸（Phe）浓度。结果：福建省1998年起开展新生儿苯丙酮尿症筛查，筛查率达10％。共筛查131402各新生儿，确诊苯丙酮尿症患儿4名（发病率1／32850万），其中1例为BH4缺乏（发病率为1／131402）。对确诊的4例PKU患儿中，3例典型PKU患儿用低苯丙氨酸饮食治疗；1例恶性PKU用四氢生物蝶呤（BH4）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。     

Pattern-reversal visual evoked potentials in phenylketonuric children

Pattern-reversal visual evoked potentials (PR-VEPs) and EEG were recorded in 14 phenylketonuric (PKU) children on a low-phenylalanine (phe) diet; the data obtained were correlated with metabolic parameters, namely, the actual phe plasma level, the mean phe plasma level in the last year, an the beginning of the diet. PR-VEPs seem to be more sensitive than EEG in detecting neurophysiological derangements in these subjects; in fact PR-VEPs were pathological in six patients while EEG detected three; no significant alterations were found in the neurophysiological tests among the children with good metabolic control, and only one child was abnormal among the six on an early dietetic regimen; in contrast, six of the nine subjects presenting with high mean phe plasma levels (>10 mg/100 ml) and five of the eight whose diet started after the 2nd month of life showed pathological PR-VEPs.     

Experimental hyperphenylalaninemia: dendritic alterations in cerebellum of rat

A quantitative analysis was made of the morphology of the cerebellar vermis in rats rendered hyperphenylalaninemic by daily injections on postnatal days 3 through 82 of the phenylalanine hydroxylase inhibitor, p-chlorophenylalanine (60 mg/kg), in combination with phenylalanine (300 mg/kg). This treatment resulted in a significant hyperphenylalaninemia (HPA) compared with saline-injected controls. In HPA animals there was a reduction in the cerebellar cross-sectional areas and in molecular layer thickness of midsagittal sections. Utilization of a classification strategy showed no specific qualitative changes in Purkinje cell structure between groups, but did indicate a hetereogeneity in Purkinje cell morphology between specific lobular sites of both HPA and control groups. Areas encompassed by Golgi-Cox-stained Purkinje cell dendritic trees were significantly smaller in HPA animals than in controls. The changes produced by HPA were of lesser degree in the nodulus than in the remaining lobes of the vermis. It is proposed that the decreased effect of HPA in the nodulus is related to normal differences in monoaminergic innervation between the nodulus and the other regions of the cerebellum.