Risk factors for recurrent respiratory tract infection in preschool-aged children.

BACKGROUND: We aimed to identify potential risk factors for recurrent respiratory tract infection among Chinese preschool-aged children, and further to construct a nomogram prediction model. METHODS: This is a cross-sectional survey conducted in Beijing. Utilizing a stratified cluster random sampling strategy, a total of 7222 children from 20 kindergartens were enrolled. Data are analyzed by STATA software and R language. RESULTS: Five independent factors were identified to be significantly associated with recurrent respiratory tract infection risk overall and by pathogenic sites. The significant odds of recurrent respiratory tract infection was 8.31 (95% confidence interval [CI]: 5.69-12.12, P < 0.001), 2.31 (2.06-2.58, P < 0.001), 1.72 (1.48-1.99, P < 0.001), 1.24 (1.08-1.43, P = 0.002), and 1.19 (1.09-1.31, P < 0.001) for asthma, allergy, initial use of antibiotics <6 months, breastfeeding duration <6 months, and maternal body mass index, respectively. Besides the leading role played by asthma, allergy, initial use of antibiotics, and breastfeeding might exert a graded, dose-dependent effect on recurrent respiratory tract infection susceptibility. CONCLUSIONS: We have identified five potential risk factors for the risk of recurrent respiratory tract infection from 7222 preschool-aged Chinese children. Notably, asthma plays a leading role, and allergy, initial use of antibiotics, and breastfeeding might exert a graded, dose-dependent effect on recurrent respiratory tract infection susceptibility. IMPACT: This is the first report of examining the joint contribution of multiple potential risk factors to recurrent respiratory tract infection among Chinese preschool-aged children. We have identified five potential risk factors for the risk of recurrent respiratory tract infection via analyzing survey data from 7222 preschool-aged Chinese children. Asthma plays a leading role, and allergy, initial use of antibiotics, and breastfeeding might exert a graded, dose-dependent effect on recurrent respiratory tract infection susceptibility.

The first study of successful pregnancies in Chinese patients with Phenylketonuria.

BACKGROUND: Since the inception of newborn screening programs in China in the 1990s, pregnancy among patients with inherited, metabolic disorders has become more common. This study explores the management and outcomes of planned, full-term pregnancies in patients with phenylketonuria (PKU). METHOD: Married patients with PKU from 2012 to 2017 were enrolled to receive prenatal counseling and regular health assessments. Study-related assessments included the timing of Phe-restricted diets, maternal weight gain, gestational age, pregnancy complications, and blood Phe concentrations (both pre-conception and during pregnancy), obstetrical data, and offspring outcomes(e.g. anthropomorphic measurements and developmental quotients [DQs]). RESULTS: A total of six offspring were successfully delivered. The mean ± SD (range) age of the mother at delivery was 26.3 ± 4.7 (range: 21.1-32.5) years. The mean duration of Phe control before pregnancy was 5.5 ± 1.3(range: 3.1-6.5) months. During pregnancy, the proportion of blood Phe concentrations within the clinically-recommended target range (120-360 µmol/L) ranged from 63.2-83.5%. Low birth weight (< 2500 g) offspring occurred in two women who experienced suboptimal metabolic control. In addition, offspring DQ was related to the proportion of blood Phe levels per trimester that were within the recommended range (r = 0.886, p = 0.016). CONCLUSION: This is the first report of women in China with PKU who successfully gave birth to clinically healthy babies. Infant outcomes were related to maternal blood Phe management prior to and during pregnancy. In maternal PKU patients with poor compliance to dietary treatment, sapropterin dihydrochloride (6R-BH4) may be an option to improve the management of blood Phe levels.

Household financial burden of phenylketonuria and its impact on treatment in China: a cross-sectional study.

BACKGROUND: Phenylketonuria (PKU) is a rare inborn disease, which, untreated, leading to severe neurobehavioral dysfunction. Considering its complexity, the management of PKU may bring a formidable economic burden to parents and caregivers. It is still unknown what the out-of-pocket expenses are for a patient with PKU in China. This paper explores the household financial burden of classical PKU and its impact on Chinese families in a quantitative manner for the first time. METHODS: A non-interventional and observational study was conducted at the China-Japan Friendship Hospital, one of the national centers for inherited metabolic disorders in China. The medical and non-medical household financial burdens were consolidated into a questionnaire to evaluate the out-of-pocket costs (OOPCs) of PKU treatment and follow-up. FINDINGS: The total OOPCs were USD$3766.1 (0y), USD$3795.2 (1-2 ys), USD$4657.7 (3-4 ys), USD$5979.9 (5-8 ys), and USD$5588.7 (9 ys and older) for PKU patients of different age groups. The median economic burden of classical PKU was 75.0 % of total annual family income (range 1.0-779.1 %), and 94.4 % of the families exceeding the threshold considered as catastrophic expenditure. There was a negative correlation between the financial burden and the proportion of time when Phe concentrations were in the desired target range (120-250 µmol/L) in 0-4-ys group (r = -0.474, p = 0.026). CONCLUSIONS: The management of PKU is associated with a severe financial burden on patients' families, which may lead to insufficient treatment or variation of blood Phe concentration. The current reimbursement policies are as yet inadequate. A national reimbursement system targeting treatment practices for PKU patients and other rare diseases across China is imperative.

Down-regulation of miR-133a-3p protects lung tissue against sepsis-induced acute respiratory distress syndrome by up-regulating SIRT1.

Introduction: MicroRNA-133a-3p (miR-133a-3p) is a potential gene regulator having an important role in the process of inflammation and lung injury. The present work studied the role of miR-133a-3p in sepsis-mediated acute respiratory distress syndrome (ARDS) and the mechanism involved. Material and methods: C57BL/6 mice were selected for the study. Protein expression of Bcl-2, cleaved caspase-3 and Bax was assessed by western blot analysis. Expression of mRNA was assessed by RT-PCR. Effects of inflammation were studied by myeloperoxidase (MPO) activity. Quantification of albumin was done by measuring the albumin conjugated with Evan's blue. The alveolar macrophages were separated from the lungs of mice by the bronchoalveolar lavage procedure and were submitted to sepsis challenge in vitro; the macrophages were treated with lipopolysaccharide (LPS). Results: Treatment of LPS resulted in upregulation of miR-133a-3p in alveolar macrophages. Suppression of miR-133a-3p halted the over-expression of inflammatory cytokines in macrophages and caused remission of histopathologic changes. The ARDS lungs showed a decrease in levels of proinflammatory cytokines and an increase in levels of apoptotic protein, establishing the protective role for miR-133a-3p. The results suggested sirtuin 1 (SIRT1) as a potential target of miR-133a-3p in the macrophages, also showing that expression of SIRT1 was inversely associated with expression of miR-133a-3p. The protective effect of miR-133a-3p down-regulation in LPS-mediated alveolar macrophages and sepsis-induced ARDS could be corrected by a SIRT1 inhibitor. Conclusions: Down-regulation of miR-133a-3p may exert a protective effect on lung tissue against sepsis-mediated ARDS by up-regulating the levels of SIRT1 via suppressing the inflammatory response and inhibiting the cellular apoptosis in lung tissues.

[Electroencephalogram evaluation of hyperphenylalaninemia patients on dietetic treatments].

OBJECTIVE: To explore the electroencephalographic changes of patients with hyperphenylalaninemia (HPA) after dietetic treatments. METHODS: From July 2005 to February 2010, 34 HPA patients with abnormal electroencephalograms were recruited from China-Japan Friendship Hospital. Their electroencephalographic results and clinical features were compared before and after dietetic and antiepileptic treatments. There were 16 males and 18 females with an age range of 2 months to 8 years. All electroencephalographic results were abnormal. Among them, there were epileptic discharges (n = 17), atypical sharp-slow wave complex (n = 1) and slow wave background (n = 16). All patients received a low intake of phenylalanine at 13-50 mg·kg(-1)·d(-1). Twenty patients had antiepileptic drug therapy. Before and after treatment for 3 months, 6 months, 1 year and 2 years, blood phenylalanine concentration, electroencephalogram, convulsion and other clinical parameters were observed. Before and after 1 year treatment, the tests of developmental quotient (DQ) or intelligence quotient (IQ) were performed. RESULTS: The phenylalanine concentrations of the same patient group decreased significantly after 3 months, 6 months, 1 and 2 years after dietetic treatment ( (0.51 ± 0.39) , (0.50 ± 0.29), (0.59 ± 0.42), (0.53 ± 0.27) vs (1.33 ± 0.64) mmol/L, all P = 0.000). Among 19 epileptic cases, 16 ceased after treatment. And 14 stayed convulsion-free within 3 months post-treatments, 2 cases had intermittent tonic-clonic seizures while there was 1 case of focal seizures. Fourteen cases withdrew antiepileptic medications or reduced their doses. After treatment, the electroencephalographic results became totally normal in 8 of the 19 epileptic cases. Electroencephalographic results improved in 5 cases versus pre-treatment. Spikes were controlled in 10 cases including 5 patients with hyperarrhythmia in the abnormal electroencephalographic group with epilepsy. Six cases continued abnormal electroencephalogram. In the abnormal electroencephalographic group without epilepsy (n = 15) , electroencephalograms were normal (n = 3), improved (n = 6) and continued mild abnormal waves (n = 2). However, there were 4 cases with deteriorated electroencephalogram and 3 of them showed spikes. DQ (IQ) was evaluated in 16 cases. And variable mental retardation was observed in all of them. After, year treatment, 7 cases were evaluated DQ (IQ), and their results showed improved (57 ± 16 vs 50 ± 16, t = -5.42, P = 0.002). CONCLUSIONS: Etiological treatment for HPA patients is important for controlling epilepsy and improving brain function. And electroencephalogram is useful for monitoring brain functions and evaluating treatment outcomes.

[Efficacy and safety of glucocorticoids in addition to intravenous immunoglobulin in the initial treatment of Kawasaki disease: a meta-analysis of randomized trials].

OBJECTIVE: To evaluate the efficacy and safety of glucocorticoids (GC) plus intravenous immunoglobulin (IVIG) in the initial treatment of Kawasaki disease. METHODS: Fourteen electronic databases and 3 Japanese magazines were searched. Randomized controlled trials (RCT) describing the use of GC plus IVIG in the initial treatment of Kawasaki disease in children were collected. The data of methodological quality and trial information were extracted by two independent researchers. Cochrane review methodology was used for assessing the trial quality and efficacy. Each dichotomous outcome was measured in terms of odds risk (OR) while continuous outcomes shown as weighted mean differences (WMD). And a meta-analysis was made with RevMan5.0.23.0 software. RESULTS: A total of 416 cases in 3 trials were included. There were 209 cases in GC + IVIG group and 207 cases in IVIG group. The incidence of coronary artery lesion (CAL) was not different between GC + IVIG and IVIG groups within 1 month or 1 month post-treatment (OR: 0.74, 0.69; 95%CI: 0.23 - 2.40, 0.35 - 1.38; P = 0.62, 0.30]. The fever duration was shorter in GC + IVIG group than that in IVIG group (WMD: -0.93 d, 95%CI: -1.15 - -0.70, P = 0.00). The treatment failure rate was less in GC + IVIG group than IVIG group (9.09% vs 17.48%, OR: 0.49, 95%CI: 0.28 - 0.86, P = 0.01). No difference in adverse events was found between two groups (OR: 0.81, 95%CI: 0.22 - 3.03, P = 0.76). CONCLUSION: There is no evidence to support that GC plus IVIG can further reduce the CAL risk of KD patients. But it may lower the treatment failure rate in KD patients.

Risk factors for allergic diseases: a cross-sectional survey of 9,501 Chinese preschool-aged children.

BACKGROUND: Childhood allergic diseases are increasing worldwide with unprecedented complexity and severity, and they cause a major burden on health and healthcare costs. We aimed to identify potential factors, both in isolation and in combination, associated with allergic diseases among preschool-aged children, and to construct a nomogram prediction model based on significant factors. METHODS: We cross-sectionally recruited 9,501 preschool-aged children from 30 kindergartens in Beijing and Tangshan. Allergic diseases were ascertained according to the "International Study of Asthma and Allergies in Childhood" questionnaire. Risk for allergic diseases is quantified by odds ratio (OR) with 95% confidence interval (CI). RESULTS: Four factors were identified to be independently, consistently, and significantly associated with the risk for allergic diseases overall and by four clinical manifestations separately, including bedtime (per 1 hour late) (taking asthma/wheezing as an example, OR, 95% CI, P: 1.21, 1.08 to 1.35, 0.001), outdoor activities ≤1.5 h per day (1.45, 1.26 to 1.68, 3.77E-07), family history of allergic diseases (2.23, 1.92 to 2.60, 0.00E+00), and antibiotic use during childhood (3.64, 2.44 to 5.42, 1.66E-10). Further analyses revealed that family history of allergic diseases acted with antibiotic use during childhood in an additive manner. For practical reasons, risk prediction nomogram models were constructed for allergic diseases respectively in Beijing and Tangshan based on significant and conventional factors, and the prediction accuracy was good, with the C-index 69% in Tangshan and 68% in Beijing (both P=0.00E+00). CONCLUSIONS: Our findings identified four factors in significant association with the risk for allergic diseases, and in particular family history of allergic diseases and antibiotic use during childhood acted additively.

Identification and Characterization of Influential Factors in Susceptibility to Attention Deficit Hyperactivity Disorder Among Preschool-Aged Children.

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder. Currently, increasing amounts of attention have been focused on the epidemiologic profiling of ADHD in children, viewed as a continuously distributed risk dimension throughout the whole lifespan. This study aimed to identify and characterize potential influential factors susceptible to ADHD-related symptoms among preschool-aged children. A comprehensive questionnaire was self-designed for both children and their parents or guardians and was distributed to 30 kindergartens from Beijing and Hebei, collecting potential influential factors in susceptibility to ADHD. ADHD was assessed by the Conner's Abbreviated Symptom Questionnaire (C-ASQ), and 7,938 children were analyzed. Least absolute shrinkage and selection operator (LASSO) regression and hierarchical degree of adjustment were used to control possible covariates. Five factors, namely, children's secondhand smoking exposure, breastfeeding duration, sleep mode, maternal pregnancy smoking exposure, and parental self-rating for patience, were identified to be independently and significantly associated with ADHD susceptibility. Meanwhile, dose-response relationships were observed between breastfeeding duration, parental self-rating for patience, and ADHD-related symptoms. Finally, a nomogram model was created for predicting ADHD susceptibility based on significant and conventional attributes under each criterion.

Identification of contributing predictors for short stature and pre-shortness among 7310 Chinese preschool-aged children.

PURPOSES: We aimed to identify the contributing predictors for short stature and pre-shortness in Chinese preschool-aged children, and further to construct nomogram prediction models. METHODS: A large cross-sectional, kindergarten-based study was conducted during September-November, 2019 in Beijing. Utilizing a stratified random sampling method, total 20 kindergartens with 7310 children with complete data were eligible for analysis. RESULTS: The prevalence of short stature and pre-shortness was 3.0% (n = 222) and 11.6% (n = 848), respectively. Six contributing predictors were significantly associated with short stature, including parental height (odds ratio, 95% confidence interval, P: 0.773, 0.69-0.86, <0.001), maternal height (0.723, 0.64-0.82, <0.001), birthweight (0.826, 0.74-0.92, 0.001), birth height (0.831, 0.69-1.00, 0.046), children body mass index (1.204, 1.43-1.82, <0.001), and maternal age at menarche (1.614, 1.43-1.82, <0.001). Seven significant contributing predictors were found for pre-shortness, including parental height (0.805, 0.76-0.85, <0.001), maternal height (0.821, 0.77-0.87, <0.001), birthweight (0.881, 0.83-0.93, <0.001), birth height (0.86, 0.78-0.95, 0.003), gestational weight gain (0.851, 0.77-0.94, 0.002), children body mass index (1.142, 1.05-1.24, 0.002), and chronic disease (4.016, 1.66-9.70, 0.002). The nomogram models for short stature and pre-shortness had descent prediction accuracies. CONCLUSIONS: Our findings indicate that short stature is predominantly determined by inherited and natal factors, and pre-shortness is additionally by modifiable factors.

Meta-analysis of metabolic changes in children with idiopathic growth hormone deficiency after recombinant human growth hormone replacement therapy.

PURPOSES: We aimed to assess the effects of recombinant human growth hormone (rhGH) replacement therapy on metabolic changes by synthesizing data from clinical trials involving children with idiopathic growth hormone deficiency (IGHD). METHODS: Two investigators independently completed literature search, quality assessment, and data extraction. Effect-size estimates are expressed as weighted mean difference (WMD) with 95% confidence interval (CI). RESULTS: A total of 16 clinical trials involving 1319 children were eligible for analysis. Overall analyses showed that total cholesterol was significantly decreased after rhGH replacement therapy (WMD: -0.20 mmol/l; 95% CI: -0.30 to -0.10; p < 0.001), and high-density lipoprotein was significantly increased (WMD: 0.29 mmol/l; 95% CI: 0.24 to 0.33; p < 0.001). Marginal increase was noted for low-density lipoprotein (WMD: -0.22 mmol/l; 95% CI: -0.47 to 0.22; p = 0.092). Subsidiary and meta-regression analyses revealed that length of intervention and sample size were possible causes of heterogeneity. There was a low probability of publication bias. CONCLUSIONS: Our findings indicate an obviously favorable role of rhGH replacement therapy in lipid metabolism in children with IGHD, and this role might be dependent on length of intervention.

Case Report: De novo KLHL24 Gene Pathogenic Variants in Chinese Twin Boys With Epidermolysis Bullosa Simplex.

Objectives: The aim of this study was to determine the molecular etiology and clinical manifestations of a pair of Chinese twins affected with epidermolysis bullosa simplex. Pediatricians should pay attention to the early genetic diagnosis of this disease. Methods: Histopathological examination of HE-stained skin, electron microscopy of biopsied normal skin, and whole-exome sequencing was performed to assess pathogenicity and conservation of detected mutations. Two years later, the cutaneous and extracutaneous manifestations of the twins were comprehensively evaluated. Results: A de novo pathogenic variant c.2T>C (p.M1T) in KLHL24 (NM_017,644) was identified in both twins. The characteristics of extensive skin defects on the extremities at birth and the tendency to lesson with increasing age were confirmed. No positive sensitive markers, such as B-type natriuretic peptide, cardiac troponin I, for cardiac dysfunction were detected. Conclusions: The de novo pathogenic variants c.2T>C (p.M1T) in KLHL24 (NM_017,644) contributes to the development of epidermolysis bullosa. Genetic diagnosis at birth or early infancy can better predict the disease prognosis and guide the treatment.

Factors Associated With Childhood Asthma and Wheeze in Chinese Preschool-Aged Children.

This study was prepared to identify and characterize potential factors associated with childhood asthma and wheeze in Chinese preschool-aged children. A comprehensive questionnaire was designed for children aged 3-6 years and their parents or guardians in Beijing and Tangshan from September to December 2020. The least absolute shrinkage and selection operator (LASSO) model was used to identify factors in a significant association with childhood asthma and wheeze, respectively. The LASSO model was internally validated using bootstrap resampling with 100 replications. A total of 9,529 questionnaires were certified as eligible for inclusion after stringent quality control. The prevalence of doctor-diagnosed childhood asthma and parent-reported wheeze was 2.8 and 6.2%, respectively. Factors simultaneously associated with childhood asthma and wheeze were children with a history of allergic rhinitis, hay fever, eczema, initial age of using antibiotics, body mass index category, and family history of asthma. Specifically, children's vitamin D supplement duration was significantly associated with childhood asthma, whereas the association with childhood wheeze was significant for intake frequency of night meals for children and their screen time. Modeling of significant factors in nomograms had decent prediction accuracies, with C-index reaching 0.728 and 0.707 for asthma and wheeze, respectively. In addition, internal validation was good, with bootstrap C-statistic of being 0.736 for asthma and 0.708 for wheeze. Taken together, our findings indicated that the development of asthma and wheeze among preschool-aged children was probably determined by the joint contribution of multiple factors including inherited, nutritional, unhealthy lifestyles, and history of allergic disease. Further validation in other groups is necessary.

Interaction effects of significant risk factors on overweight or obesity among 7222 preschool-aged children from Beijing.

OBJECTIVES: We aimed to identify potential risk factors, both individually and interactively, associated with overweight and obesity among preschool-aged children, and further to create a risk prediction nomogram model. RESULTS: After graded multivariable adjustment, maternal body mass index (BMI) (odds ratio, 95% confidence interval, P under China criteria: 1.07, 1.05 to 1.10, <0.001), maternal pre-pregnancy BMI (1.08, 1.05 to 1.10, <0.001), breastfeeding duration (0.86, 0.76 to 0.98, 0.019), and sleep duration (0.95, 0.90 to 1.00, 0.042) were found to be independently and consistently associated with the significant risk of childhood overweight or obesity under three different growth criteria. Further analyses revealed the four significant factors acted in an additive manner, especially for the interaction between maternal obesity, sleep duration, and breastfeeding. Finally, a risk prediction nomogram model was created for childhood overweight or obesity based on significant and conventional attributes under each criterion. CONCLUSIONS: Our findings provide evidence that the four significant factors are associated with the risk of childhood overweight or obesity in an additive manner. METHODS: Using a stratified cluster random sampling strategy, 7222 preschool-aged children were analyzed. Childhood overweight and obesity are defined according to the China criteria and two widely-used international growth criteria.

Pre-pregnancy Maternal Weight and Gestational Weight Gain Increase the Risk for Childhood Asthma and Wheeze: An Updated Meta-Analysis.

Background: Mounting evidence suggests that childhood asthma is closely associated with maternal weight before pregnancy and gestational weight gain (GWG), yet the results are not often reproducible. Objectives: We conducted a comprehensive meta-analysis, aiming to evaluate the association of pre-pregnancy maternal obesity or overweight and high GWG with the risk for childhood asthma and wheeze. Methods: Literature search, quality assessment, and data extraction were completed independently and in duplicate. Effect-size estimates are expressed as odds ratio (OR) with 95% confidence interval (CI). Results: Twenty-two observational studies involving 145,574 mother-child pairs were meta-analyzed. In overall analyses, maternal obesity or overweight in pre-pregnancy significantly increased the risk of both childhood asthma and wheeze (adjusted OR: 1.41 and 1.13, 95% CI: 1.26-1.59 and 1.07-1.20, both p < 0.001). Per 1 kg/m2 increment in maternal body mass index was associated with a significantly increased risk of childhood asthma and wheeze (adjusted OR: 1.03, 95% CI: 1.02-1.03, p < 0.001). Compared with normal GWG, very high GWG (adjusted OR: 1.24, 95% CI: 1.04-1.47, p: 0.018), moderate high GWG (adjusted OR: 1.12, 95% CI: 1.04-1.21, p: 0.004), and very low GWG (adjusted OR: 1.26, 95% CI: 1.08-1.47, p: 0.004) increased the risk of childhood asthma and wheeze. There was a low probability of publication bias. Conclusions: Our findings indicate that both pre-pregnancy maternal obesity or overweight and very to moderate high or low GWG render their offspring susceptible to a significantly increased risk of having childhood asthma and wheeze.

Fibrinogen is a promising biomarker for chronic obstructive pulmonary disease: evidence from a meta-analysis.

BACKGROUNDS: Some studies have reported association of circulating fibrinogen with the risk of chronic obstructive pulmonary disease (COPD), and the results are conflicting. To yield more information, we aimed to test the hypothesis that circulating fibrinogen is a promising biomarker for COPD by a meta-analysis. METHODS: Data extraction and quality assessment were independently completed by two authors. Effect-size estimates are expressed as weighted mean difference (WMD) with 95% confidence interval (95% CI). RESULTS: Forty-five articles involving 5586/18604 COPD patients/controls were incorporated. Overall analyses revealed significantly higher concentrations of circulating fibrinogen in COPD patients than in controls (WMD: 84.67 mg/dl; 95% CI: 64.24-105.10). Subgroup analyses by COPD course showed that the degree of increased circulating fibrinogen in patients with acute exacerbations of COPD (AECOPD) relative to controls (WMD: 182.59 mg/dl; 95% CI: 115.93-249.25) tripled when compared in patients with stable COPD (WMD: 56.12 mg/dl; 95% CI: 34.56-77.67). By COPD severity, there was a graded increase in fibrinogen with the increased severity of COPD relative to controls (Global Initiative for Obstructive Lung Disease (GOLD) I, II, III, and IV: WMD: 13.91, 29.19, 56.81, and 197.42 mg/dl; 95% CI: 7.70-20.11, 17.43-40.94, 39.20-74.41, and -7.88 to 402.73, respectively). There was a low probability of publication bias. CONCLUSION: Our findings indicate a graded, concentration-dependent, significant relation between higher circulating fibrinogen and more severity of COPD.

Reduced bone mineral density in Chinese children with phenylketonuria.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive metabolic disorder. Dietary control of classic PKU needs restriction of natural proteins. The diet results in unbalanced nutrition, which might affect the physical development of the patients. Our aim was to evaluate bone mineral density (BMD) in children with PKU. METHODS: To investigate the BMD of children with PKU, 41 children with PKU and 64 healthy controls were recruited (all 3-4 years of age). Body weight and height, BMD, Phe blood levels, thyroid function, calcium, phosphorus, iron metabolism markers, and vitamin D3 were measured. RESULTS: Body height and BMD of patients were lower than in controls. The BMD of controls was positively associated with age, body weight and height. In patients, BMD was positively associated with body weight. There was no correlation between Phe blood levels and BMD in patients. Blood levels of alkaline phosphatase were higher in patients compared to controls. Blood calcium levels were higher in 4-year-old patients, while the body weight was lower compared to controls. Thyroid function, iron metabolism markers, vitamin D3 levels and IGF-1 levels were normal. CONCLUSIONS: Reduced BMD was observed in children with phenylketonuria, but the exact reasons for this remain to be elucidated.

[Quantification of phenylalanine in the brain of patients with hyperphenylalaninemia by (1)H magnetic resonance spectroscopy].

OBJECTIVE: Hyperphenylalaninemia (HPA) is an inborn error of metabolism in which the hydroxylation of phenylalanine (Phe) to tyrosine is disturbed. Accumulation of Phe leads to severe mental and psychomotor retardation. (1)H magnetic resonance spectroscopy ((1)HMRS) is a novel non-invasive method to quantitate the brain metabolites besides Phe concentration in HPA patients. And it could be acquired conveniently on clinical MRI routine scanners. This study aimed to investigate the correlation between blood Phe ([Phe](blood)) and [Phe](brain), the characteristics of blood-brain Phe metabolism and its impacts on mental retardation. METHOD: Totally 32 untreated patients diagnosed with HPA were studied, including 18 boys and 14 girls (age ranging from 33 days to 13 years). The patients were divided into two groups: elder than 4 months old (n = 22) and younger than 4 months old (n = 10). (1)HMRS were performed in all patients. [Phe](brain) were measured by absolute [Phe](brain) using Creatinine as an internal reference. [Phe](blood) were measured and developmental quotient (DQ) or intelligence quotients (IQ) were evaluated. RESULT: (1) [Phe](brain) measured by (1)HMRS ranged from 0.0640 to 0.6296 (M = 0.1542) while the [Phe](blood) was from 0.3804 to 2.5140 mmol/L (M = 1.5210 mmol/L) in all the 32 cases of HPA patients. (2) There was a positive linear correlation (r = 0.6103 (P < 0.01)) between [Phe](blood) and [Phe](brain). And there were interindividual differences in [Phe](brain) in several patients. (3) Variable mental retardation were observed in 23/32 cases in this study. (4) There was a negative correlation between [Phe](blood) and [Phe](brain) to the mental retardation (r(blood) = -0.5045, r(brain) = -0.6471 (P < 0.01)) in 22 cases of the HPA patients older than 4 months. And [Phe](brain) had more significant correlation with mental development than [Phe](blood). CONCLUSION: The [Phe](blood) could correspondingly represent the [Phe](brain) in most HPA patients. The Phe concentration could reflect the degree of mental retardation substantially in 22 cases with HPA older than 4 months. And the [Phe](brain) could more accurately illustrate it. (1)HMRS can be used to quantitate intracerebral Phe concentrations non-invasively in HPA patients. Preliminary findings suggest that interindividual variations in the kinetics of Phe uptake and metabolism do exist. (1)HMRS has great clinical significance in understanding the mechanism of HPA patient's mental retardation, providing proper objective standards for better diagnosis and treatment of HPA patients.