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Background Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is one of the most common autoimmune encephalitis in children. Most children recovered well after anti-NMDA receptor encephalitis. However, the NMDA receptor network functions are critical for the developing brain in children. The long-term consequences in pediatric patients of anti-NMDA receptor encephalitis are very infrequently reported. Methods This case series study retrospectively enrolled 10 children aged below 18 years old with antibody-proved anti-NMDA receptor encephalitis in a tertiary medical center from 2010 to 2019. Long-term neurological consequences of anti-NMDA receptor encephalitis in children were followed. Results One boy and nine girls were enrolled with a median onset age of 3.6 years. The most common initial presentation was verbal reduction and psychiatric symptoms soon after some flu-like prodromal symptoms. Nearly all patients then developed decreased level of consciousness, mutism, seizures and orofacial-lingual dyskinesia. Autonomic instability occurred in 5 patients, particularly in pre-pubertal children. Only one adolescent patient had ovarian teratoma. All patients survived after immunotherapy and were followed for 5.8 ± 3.3 years after discharge. Four had epilepsy within 2 years after encephalitis, four had a cognitive deficit, one had mild psychiatric symptoms of hallucination, and none had residual involuntary movements. Moreover, two pre-pubertal children developed central precocious puberty about 3 years after encephalitis, and one required gonadotropin-releasing hormone agonist treatment. Conclusion Central precocious puberty could be a consequence of anti-NMDA receptor encephalitis in the pre-pubertal children. The pediatrician should pay attention to its occurrence at follow-up.

Previous studies have shown hypothyroidism was independently associated with nonalcoholic fatty liver disease (NAFLD) in adults, but few studies examined their relationships in pediatric populations. This study aimed to investigate the prevalence of NAFLD in pediatric congenital hypothyroidism (CHT) patients and to identify the association between CHT and NAFLD. This study enrolled pediatric CHT patients receiving levothyroxine treatment at one medical center from 2013 to 2014. Euthyroid subjects (ET) and transient hypothyroidism (THT) patients weaned off medication successfully after age 3 were selected for further comparison. Laboratory data including thyroid functions, liver functions, and metabolic profiles were obtained. The major outcome was the occurrence of NAFLD, diagnosed based on the findings of abdominal ultrasonography. One‐hundred and twenty‐nine subjects (47 in CHT, 47 in THT, and 35 in ET groups) were enrolled. The analysis showed higher fasting serum glucose, insulin, thyroxine (T4), and mean thyroid‐stimulating hormone (TSH) levels in the CHT group. NAFLD prevalence was higher in the CHT (23.4%) group than in the THT (8.5%) and the ET (5.7%) groups, demonstrating an increasing trend across three strata (X2linear‐by‐linear = 5.9, P

Background: Silver–Russell syndrome (SRS) is a clinically and genetically heterogeneous disorder characterized by severe intrauterine growth retardation, poor postnatal growth, characteristic facial features, and body asymmetry. Hypomethylation of the imprinted genes of the chromosome 11p15.5 imprinting gene cluster and maternal uniparental disomy of chromosome 7 (mUPD7) are the major epigenetic disturbances. The aim of this study was to characterize the epigenotype, genotype, and phenotype of these patients in Taiwan. Methods: Two hundred and six subjects with clinically suspected SRS were referred for diagnostic testing, which was performed by profiling the methylation of H19-associated imprinting center (IC) 1 and the imprinted PEG1/MEST region using methylation-specific multiplex ligation-dependent probe amplification and high-resolution melting analysis with a methylation-specific polymerase chain reaction assay. We also applied a whole genome strategy to detect copy number changes and loss of heterozygosity. Clinical manifestations were recorded and analyzed according to the SRS scoring system proposed by Bartholdi et al. Results: Among the 206 referred subjects, 100 were classified as having a clinical diagnosis of SRS (score ≥ 8, maximum = 15) and 106 had an SRS score ≤ 7. Molecular lesions were detected in 45% (45/100) of the subjects with a clinical diagnosis of SRS, compared to 5% (5/106) of those with an SRS score ≤ 7. Thirty-seven subjects had IC1 hypomethylation, ten subjects had mUPD7, and three subjects had microdeletions. Several clinical features were found to be statistically different (p &lt, 0.05) between the “IC1 hypomethylation” and “mUPD7” groups, including relative macrocephaly at birth (89% vs. 50%), triangular shaped face (89% vs. 50%), clinodactyly of the fifth finger (68% vs. 20%), and SRS score (11.4 ± 2.2 vs. 8.3 ± 2.5). Conclusions: The SRS score was positively correlated with the molecular diagnosis rate (p &lt, 0.001). The SRS subjects with mUPD7 seemed to have fewer typical features and lower SRS scores than those with IC1 hypomethylation. Careful clinical observation and timely molecular confirmation are important to allow for an early diagnosis and multidisciplinary management of these patients.

Background: Beckwith-Wiedemann syndrome (BWS, OMIM 130650) is a rare overgrowth syndrome with tumor predisposition resulting from the abnormal expression or function of imprinted genes of the chromosome 11p15.5 imprinting gene cluster. The aim of this study was to identify the epigenotype-phenotype correlations of these patients using quantitative DNA methylation analysis. Methods: One hundred and four subjects with clinically suspected BWS were enrolled in this study. All of the subjects had been referred for diagnostic testing which was conducted using methylation profiling of H19-associated imprinting center (IC) 1 and KCNQ1OT1-associated IC2 in high-resolution melting analysis and methylation quantification with the MassARRAY assay. Correlations between the quantitative DNA methylation status and clinical manifestations of the enrolled subjects were analyzed. Results: Among the 104 subjects, 19 had IC2 hypomethylation, 2 had IC1 hypermethylation, and 10 had paternal uniparental disomy (pUPD). The subjects with IC2 hypomethylation were characterized by significantly more macroglossia but less hemihypertrophy compared to the subjects with pUPD (p &lt, 0.05). For 19 subjects with IC2 hypomethylation, the IC2 methylation level was significantly different (p &lt, 0.05) between the subjects with and without features including macroglossia (IC2 methylation level: 11.1% vs. 30.0%) and prenatal or postnatal overgrowth (8.5% vs. 16.9%). The IC2 methylation level was negatively correlated with birth weight z score (p &lt, 0.01, n = 19) and birth height z score (p &lt, 0.05, n = 13). For 36 subjects with clinically diagnosed BWS, the IC2 methylation level was negatively correlated with the BWS score (r = −0.592, p &lt, 0.01). The IC1 methylation level showed the tendency of positive correlation with the BWS score without statistical significance (r = 0.137, p &gt, 0.05). Conclusions: Lower IC2 methylation and higher IC1 methylation levels were associated with greater disease severity in the subjects with clinically diagnosed BWS. Quantitative DNA methylation analysis using the MassARRAY assay could improve the detection of epigenotype-phenotype correlations, which could further promote better genetic counseling and medical care for these patients.

Background and Objectives: Insulin treatment may be initially required to stabilize patients presenting with metabolic crisis at type 1 and 2 diabetes mellitus (DM) onset. Some patients with type 2 DM may need persistent insulin treatment. This study aimed to examine the predictive performance of non-stimulated C-peptide level at the time of diagnosis for future insulin use in pediatric diabetic patients. Materials and Methods: We reviewed the medical charts of diabetic patients aged 18 years or younger in a medical center in southern Taiwan from January 2000 to December 2019. Clinical and individual data were collected at the time of DM diagnosis. Outcomes were persistent insulin use at the time of diagnosis, as well as at one and two years after diagnosis. Results: The final analysis included a total of 250 patients. The best cut-off point of non-stimulated C-peptide was 0.95 ng/mL, and the predictive indices for the insulin use were 0.84 for sensitivity and 0.94 for specificity at two years after DM diagnosis. Incorporating age at onset and presence of GAD antibodies can further increase the predictive power of non-stimulated C-peptide. Conclusions: The value of non-stimulated C-peptide at diabetic onset was feasible and effective for predicting future insulin treatment up to the time point of two years after diagnosis.

Collagenopathy is a rare genetic condition characterized by abnormality in either collagen structure or metabolism. Variations in its clinical presentations highlight diversity in the genetic causes and potential existence of concurrent mutations. Through whole exome sequencing (WES) complemented with multiplex ligation-dependent probe amplification, we identified the genetic etiologies for six cases with osteogenesis imperfecta (OI) in COL1A1 (p.T1298N, p.Q1280Pfs∗51, and p.G557Vfs∗23) and COL1A2 (c.1-1677_133-441del) as well as three cases with spondyloepiphyseal dysplasia congenita in COL2A1 (p.G1041S, p.G654S, and p.G441A). Co-occurrence of COL1A1 and WNT1 mutations was found in a patient with a mild OI phenotype but severe osteoporosis. These findings extended the pathogenic variant spectrum of COL1A1, COL1A2, and COL2A1 for type I and type II collagenopathies. Although WES provides a fast and accurate method to identify the genetic causes in most of the patients with type I and type II collagenopathies, its limitation of detecting CNVs because of variable capturing uniformity should be kept in mind when interpreting the results. Taken together, we demonstrate that multiple genetic characterizing technologies can provide an accurate and efficient molecular diagnostic of new genetic variants in disease-causing genes that are compatible with clinical phenotypes.

Primary congenital hypothyroidism is a disease associated with low serum thyroxine and elevated thyroid-stimulating hormone (TSH) levels. The processes of screening and treating congenital hypothyroidism, in order to prevent neurodevelopmental impairment (NDI) in newborns, have been well investigated. Unlike term infants, very preterm infants (VPIs) may experience low thyroxine with normal TSH levels (&lt, 10.0 μIU/mL) during long-stay hospitalization. In the current literature, thyroxine treatment has been evaluated only for TSH-elevated VPIs. However, the long-term impact of low thyroxine levels in certain VPIs with normal TSH levels deserves more research. Since July 2007, VPIs of this study unit received screenings at 1 month postnatal age (PNA) for serum TSH levels and total thyroxine (TT4), in addition to two national TSH screenings scheduled at 3–5 days PNA and at term equivalent age. This study aimed to establish the correlation between postnatal 1-month-old TT4 concentration and long-term NDI at 24 months corrected age among VPIs with serial normal TSH levels. VPIs born in August 2007–July 2016 were enrolled. Perinatal demography, hospitalization morbidities, and thyroid function profiles were analyzed, and we excluded those with congenital anomalies, brain injuries, elevated TSH levels, or a history of thyroxine treatments. In total, 334 VPIs were analyzed and 302 (90.4%) VPIs were followed-up. The postnatal TT4 concentration was not associated with NDI after multivariate adjustment (odd ratios 1.131, 95% confidence interval 0.969–1.32). To attribute the NDI of TSH-normal VPIs to a single postnatal TT4 concentration measurement may require more research.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is a rare mitochondrial disease caused by biallelic mutations in COQ4. Here we report the largest cohort of COQ10D7 to date, with 11 southern Chinese patients confirmed with biallelic COQ4 mutations. Five of them have the classical neonatal-onset encephalo-cardiomyopathy, while the others have infantile onset with more heterogeneous clinical presentations. We also identify a founder mutation COQ4 (NM_016035.5): c.370G>A, p.(Gly124Ser) for COQ10D7, suggesting a higher chance of occurrence in the southern Chinese. This study helps improve understanding of the clinical spectrum of this disorder.

Background Information regarding the long-term outcome of enzyme replacement therapy (ERT) with recombinant human N-acetylgalactosamine 4-sulfatase (rhASB, galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.) for Taiwanese patients with mucopolysaccharidosis (MPS) VI is limited. Methods Nine Taiwanese patients with MPS VI (4 males and 5 females; age range, 1.4 to 21.1 years) treated with weekly intravenous infusions of galsulfase (1.0 mg/kg) in 5 medical centers in Taiwan were reviewed. A set of biochemical and clinical assessments were evaluated annually. Results After 6.2 to 11.2 years of galsulfase treatment, 6 patients experienced improvement over baseline in the 6-minute walk test by a mean of 150 m (59% change over time), and 3 patients also increased the 3-minute stair climb test by a mean of 60 steps (46%). In a manual dexterity test, 3 patients decreased the time required to pick up 10 coins and put the coins into a cup by 15 s (33%). Shoulder range of motion in all 9 patients improved, and Joint Pain and Stiffness Questionnaire scores improved by 0.42 points (21%). Four patients showed improved pulmonary function. Five patients had positive effects on cardiac-wall diameters. Four patients had improved cardiac diastolic function. Liver and spleen sizes as measured by abdominal ultrasonography remained the same or decreased in all 9 patients. However, the severity degree of valvular stenosis or regurgitation did not show improvement despite ERT. A mean overall 69% decrease in urinary glycosaminoglycan (GAG) excretion indicated a satisfactory biomarker response. Conclusions Long-term ERT was beneficial and safe for Taiwanese patients with MPS VI. This treatment reduced urinary GAG and had positive effects on a wide range of clinical functional assessments including endurance, mobility, joint function, pulmonary function, liver and spleen size, cardiac hypertrophy and diastolic dysfunction., Highlights • Nine Taiwanese MPS VI patients treated with weekly intravenous infusions of galsulfase for 6.2 to 11.2 years were reviewed. • Long-term ERT was beneficial and safe for Taiwanese patients with MPS VI. • Long-term ERT reduced urinary GAG and had positive effects on a wide range of clinical functional assessments.

Alström syndrome (AS) is a rare autosomal recessive disorder that shares clinical features with other ciliopathy-related diseases. Genetic mutation analysis is often required in making differential diagnosis but usually costly in time and effort using conventional Sanger sequencing. Herein we describe a Taiwanese patient presenting cone-rod dystrophy and early-onset obesity that progressed to diabetes mellitus with marked insulin resistance during adolescence. Whole exome sequencing of the patient's genomic DNA identified a novel frameshift mutation in exons 15 (c.10290_10291delTA, p.Lys3431Serfs*10) and a rare mutation in 16 (c.10823_10824delAG, p.Arg3609Alafs*6) of ALMS1 gene. The compound heterozygous mutations were predicted to render truncated proteins. This report highlighted the clinical utility of exome sequencing and extended the knowledge of mutation spectrum in AS patients.

Background Hyperglycemia is common during treatment for pediatric acute lymphoblastic leukemia (ALL). Several risk factors have been proposed, but emergence of new evidence suggests conflicting results. In view of ethnic differences in the propensity for diabetes, this study aims to delineate the characteristics of pediatric patients at risk for hyperglycemia during chemotherapy in Taiwan. Methods This retrospective study involved chart review of consecutive patients younger than 18 years with diagnosis of ALL in a medical center in Taiwan from 1997 to 2008. Hyperglycemia was defined by random plasma glucose levels ≥200 mg/dL or fasting glucose levels ≥126 mg/dL in at least two separate samplings. Risk factors for hyperglycemia were described with crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) in the univariate and multivariate regression analysis. Results A total of 133 patients were included for analysis. Overall, 22 patients (16.5%) experienced hyperglycemia during ALL treatment. Most hyperglycemic episodes occurred within the first 8 days after prednisolone use. Age older than 10 years was the most important predictor of hyperglycemia (adjusted OR = 10.88, 95% CI 2.40–49.37). Patients with fasting glucose concentration ≥100 mg/dL were also 5.7-fold (95% CI 1.63–19.93) more likely to develop hyperglycemia, whereas the predictive significance of obesity was attenuated after adjustment. Conclusion Assessment of glucose concentration should be vigilant in the 1st week after prednisolone use during ALL treatment. Clinicians should be alert to the patient at risk of hyperglycemia, particularly obese adolescents with disarranged glucose homeostasis.

Prader-Willi syndrome (PWS) is a genetic disorder with obesity, developmental delay, short stature, and behavioral abnormalities. The study aimed to assess the functional independence in children with PWS. The Functional Independence Measure for Children (WeeFIM) was used to evaluate 81 children with PWS (44 boys and 37 girls) with a median age of 11 years 1 month (range 2 years 8 months to 20 years 2 months) were recruited between January 2013 and December 2016. The mean total WeeFIM score was 103.8 (maximum 126). Sixty-five patients (80%) had deletion type PWS, 16 (20.0%) had nondeletion type. The scores were 103.6 ± 18.5 for deletion and 104.8 ± 18.3 for nondeletion type (p = .405), 104.8 ± 19.3 in boys and 102.6 ± 17.3 in girls (p = .293). The mean self-care, mobility, and cognition scores were 47 (maximum 56), 33 (maximum 35), and 24 (maximum 35), respectively. All total scores and 18 subscores in the three functional domains were positively correlated with age (p < .05). Most children required assistance in problem-solving, comprehension, and expression. The WeeFIM identified the strengths and limitations of children with PWS and confirmed that support and supervision were needed in cognitive and self-care tasks.

Background Little is known about the metabolic factors associated with the health-related quality of life (HRQOL) among obese youths. The aim of this study is to assess metabolic correlates of HRQOL in a clinical sample of Taiwanese overweight and obese (OW/OB) adolescents. Methods OW/OB adolescents (age 11–19 years) were recruited and compared to their normal-weight counterparts in a tertiary hospital. HRQOL was assessed by the Pediatric Quality of Life Inventory (PedsQL). Student t tests and Cohen’s d were used to compare the differences in the PedsQL scores between normal-weight and OW/OB participants who were stratified by their cumulative number of cardiometabolic risk factors (CRF). Pearson’s correlation and multivariate linear regression analyses were applied to identify predictors of PedsQL. Results OW/OB adolescents (n = 60) reported lower PedsQL scores than those of normal-weight peers. The negative effects were even larger in OW/OB participants with more than one CRF. Body mass index z-scores and serum alanine aminotransferase (ALT) levels were negatively correlated with overall and subscales of PedsQL (r = − 0.283 to − 0.431). Multivariate linear models showed ALT to be the most salient factor associated with poor obesity-related HRQOL. Conclusion Taiwanese OW/OB adolescents, particularly those having additional CRF, reported worse HRQOL. Impaired liver functions may predispose OW/OB subjects to even worse HRQOL.

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is characterized by conjugated hyperbilirubinemia and increased plasma bile acid concentrations. However, the underlying mechanisms remain unclear. We established a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneously quantifying plasma bile acids and examined bile acid profiles in NICCD infants.We measured 15 bile acids within 15min and found a wide linear range for individual bile acids.The within-run and run-to-run CV of all bile acids was 1.2-10.9% and 3.1-10.8%, respectively, with a mean recovery of 90.5-112.6%. Compared to infants with citrullinemia without mutations in SLC25A13 (non-NICCD), NICCD infants showed increased plasma total bile acid concentrations (mean: 201 vs. 42μM, p0.001), with a distinct bile acid profile characterized by increased conjugated primary bile acid concentrations. The calculated ratios, including primary/secondary bile acid (714 vs. 235, p0.05) and conjugated/free bile acid (371 vs. 125, p0.05) ratios, were higher in NICCD infants. The area under receiver operating characteristic curve for conjugated/free bile acid ratio to identify infants with NICCD was 0.871 (95% confidence interval, 0.713-1.0).Together, our findings indicated plasma bile acid profile as a potential noninvasive diagnostic biomarker for NICCD.

study question: Is there an association between exposure to phthalates and the timing of female puberty? summaryanswer: Our study suggests that the early onset of puberty is related to increased kisspeptin secretion. what is known already: Girls are maturing earlier than in past decades and the quantity of phthalates used in consumer products has concurrently risen. The hypothesis that exposure to phthalates may increase kisspeptin secretion and thereby cause early-onset puberty is unexplored. studydesign,size,duration: This case– control study ran from 2006 to 2009. We enrolled 104 girls. Girls in the central precocious puberty (CPP) (case) group were recruited from a pediatric endocrinology policlinic in Taiwan; prepubescent controls were recruited from local elementary schools and all were categorized based on a pediatrician’s diagnosis. participants/materials, setting, methods: The physical characteristics of puberty were assessed and levels of LH, FSH estradiol and kisspeptin-54 in blood samples were evaluated using radioimmunoassay. Reversed-phase high-performance liquid chromatography-tandem mass spectrometry was used to analyze seven urinary phthalate metabolites. Non-parametric analyses, trend tests and linear regressions were performed on the data. main results and the role of chance: All seven urinary phthalate metabolites in the CPP group were significantly (P , 0.05) higher than in prepubescent controls. Serum kisspeptin-54 levels were higher (P ¼ 0.022) in the CPP group than controls and were still significantly higher after adjusting for age (P ¼ 0.03). There was a significant increasing trend (Ptrend ¼ 0.005) between levels of kisspeptin and the stages of puberty. The concentration of kisspeptin-54 did not change in girls treated with leuprorelin acetate. There was a significant positive correlation between kisspeptin-54 and urinary mono-n-butyl phthalate (ng/ml: R 2 ¼ 0.251, P , 0.001; mg/g-creatinine: R 2 ¼ 0.109, P ¼ 0.024). limitations, reasons forcaution: The study duration was short and the sample size relatively small; therefore, we were unable to collect sufficient evidence to support the temporality between exposure to phthalates and the subsequent occurrence of PP. wider implications of the findings: Kisspeptin may promote the onset of puberty in girls who are exposed to a high level of phthalates, especially di-n-butyl phthalate. These data suggest that developing a kisspeptin antagonist might be an alternative strategy for treating PP.

Background Earlier adiposity rebound (AR) is correlated with obesity. Our goal is to examine rates of obesity and AR in congenital hypothyroidism (CHT) and analyze the risk factors of obesity. Methods We retrospectively reviewed the cases with abnormal newborn screens of thyroid-stimulating hormone (TSH) from 1990 to 2005 and enrolled permanent CHT patients who continued to receive treatment after the 3 rd year of life. We determined subgroups of obesity/being overweight and normal body mass index (BMI) by the latest BMI at 6–7 years of age. BMI at each age and the age of AR were compared with the general population in Taiwan. The statistical correlation of obesity with the age and BMI at both AR and first peak, and thyroid function was calculated. Results A total of 90 cases of CHT were enrolled. The prevalence of obesity/being overweight was 32.2%. The age of AR was 4.94 ± 1.81 and 4.58 ± 1.86 years old in boys and girls, respectively. The age of AR in the girls with CHT was earlier than in girls in general, but no statistical significance was found in boys with CHT compared to the general population. Obesity was correlated with earlier age of AR, higher BMI at first peak and AR, and lower T4 after treatment, but not with the age of first peak of BMI, T4/TSH at diagnosis and AR, and TSH after treatment. Conclusion Children with CHT have a higher risk of obesity due to earlier age of AR. We recommend that supervision and intervention on weight control should be provided to prevent the occurrence of obesity later.

Campomelic dysplasia (CD) is a rare autosomal dominant skeletal malformation with or without sex reversal. About 10% of cases that present with milder skeletal features are referred to as acampomelic campomelic dysplasia (ACD). CD and ACD are caused by mutations in SOX9. We report a patient of homozygous SOX9 deletion with minimal skeletal anomaly and female external genitalia in the presence of a male karyotype. The mechanisms explaining the homozygous deletion include a de novo mutation followed by gene conversion, uniparental disomy, or somatic crossing over. Our report highlights the possibility of ACD in XY sex-reversed patients with minimal skeletal presentation.

Monosomy 9p syndrome, also known as Alfi syndrome, has been described as a contiguous syndrome characterized by mental retardation, developmental delay, and facial dysmorphisms. Males with monosomy 9p often express variable degrees of feminization, although the genitalia of females will be normal. In the present report, we describe a case of ambiguous genitalia and intra-abdominal testicular development, with a derivative chromosome 9 arising from a translocation between 9p23 and Yq heterochromatin. Pathologic examination of the testes showed germ cell hypoplasia of the seminiferous tubules. fluorescence in situ hybridization, spectral karyotyping, and array comparative genomic hybridization were used to characterize the genetic changes.

Phthalates are developmental and reproductive toxicants for the fetus in pregnant rodents, and the ability of phthalates to penetrate the placenta have been reported. The aims of this study were to evaluate the association between maternal urine excretion, the exposure of fetus to phthalates in amniotic fluid, and the health of newborns. Amniotic fluid and urine samples from pregnant women were collected to measure five phthalate monoesters using liquid chromatography/tandem mass spectrometry (LC/MS-MS) and the newborns' birth weight, gestational age, and anogenital distance (AGD) were collected. The median levels of three phthalate monoesters in urine and amniotic fluid were 78.4 and 85.2 ng/mL monobutyl phthalate (MBP); 24.9 and 22.8 ng/mL mono-(2-ethylhexyl) phthalate (MEHP); 19.8 and Not Detected monoethyl phthalate (MEP). We found a significant positive correlation only between creatinine adjusted urinary MBP and amniotic fluid MBP (R2=0.156, p

Background Propionyl-CoA carboxylase (PCC) is a mitochondrial enzyme involved in the catabolism of several essential amino acids and odd chain fatty acids. Previous PCC assays have involved either a radiometric assay or have required mitochondria isolation and/or enzyme purification. Methods We developed an enzymatic method to analyze PCC activity in phytohemagglutinin (PHA) stimulated lymphocytes that involves high performance liquid chromatography. Results The method shows good linearity and sensitivity. PCC activity was unaffected even when lymphocytes were isolated and PHA stimulated after a whole blood sample had been stored at 4 °C for 5 days. This indicates that this method is suitable for analyzing samples from distant medical centers. The PCC activity of patients with propionic acidemia was found to be much lower than that of normal individuals and carriers. However, this PCC assay is significantly affected by the red blood cell contamination. In conclusion, this is a reliable method for performing PCC assays and only requires 0.5 to 1.0 ml of whole blood from newborns. Conclusions The PCC assay established in this study is useful for the confirmation of PA in individuals, and prenatal diagnosis and genetic counseling for the affected families.

521.59 per 100,000 enrollees (95% CI 514.89-528.59) and 3.24 per 100,000 enrollees (95% CI 2.71-3.77), respectively. No remarkable sexual difference in the annual incidence of type 1 DM was noted, whereas a male/female ratio of 0.85 (95% CI 0.82-0.88) in the prevalence was observed. The annual incidence of type 1 DM decreased with age and remained stable over these 10 years; while the prevalence remained constant through adolescence and varied from year to year. Meanwhile, the adjusted prevalence and mean annual incidence of type 2 DM were 834.14/100,000 (95% CI 825.64-842.63) and 120.19/100,000 (95% CI 116.96123.43), respectively. No remarkable sexual predominance in the prevalence of type 2D M was noted, whereas am ale/ female ratio of 0.86 (95% CI 0.79-0.92) was observed in the prevalence. The annual incidence of type 2 DM increased with age and decreased gradually over the recent 10 years; while the prevalence was still on the increase in this age group.

Human exposure to phthalates, which are endocrine disrupting chemicals (EDCs), is ubiquitous in the human environment because of their wide use in plastics and other common consumer products. General populations are exposed to phthalates via ingestion, inhalation, dermal absorption, and medical treatment. The potential consequences of human exposure to phthalates have raised concerns in the general population and have been widely studied in susceptible subjects, such as pregnant women, infants, and children. In vitro studies showed that phthalate esters may disrupt our endocrine system via interaction with estrogen receptor-α and -β and androgen receptor. Animal studies showed that phthalate esters interfere with development of the male reproductive system of rodents when administered during a critical window in gestation and cause a syndrome similar to testicular dysgenesis syndrome. Some phthalate esters alter the onset of puberty in prepubertal female rodents and change ovarian function in adult female rodents. In human studies, evidence showed that phthalates may cause changes in gestational age and birth weight after prenatal exposure in humans. Prenatal exposure to phthalates may change the anogenital distance and reproductive hormones in humans through anti-androgenic effects on the fetus. Moreover, phthalates may play a role in pubertal development of adolescent females. Since children and infants may be more susceptible to phthalates, it is suggested that parents buy toys and use personal products that are labeled phthalate free. More studies to investigate the underlying mechanism and the impact of phthalate esters on children’s growth and development should be done.

Background Citrin, encoded by SLC25A13 gene, is a mitochondrial solute transporter with a crucial role in urea, nucleotide and protein synthesis. SLC25A13 mutations cause two phenotypes, adult-onset type II citrullinemia and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). This study aimed to develop a high resolution melting (HRM) analysis for SLC25A13 mutation scanning and determine the carrier rate in Taiwan. Methods DNAs from healthy subjects (n = 479), and patients with hepatocellular carcinoma (HCC, n = 100) and NICCD (n = 5) were scanned in exons 6, 9, 11, 16, and 17 and parts of introns of SLC25A13 using HRM analysis. All mutations detected by HRM analysis were further confirmed by TaqMan method and/or direct sequencing. Results In healthy subjects, seventeen carriers with mutants c.851_854del (n = 10), c.1638_1660dup, c.615 + 5G > A (n = 4), and two novel mutants, c.475C > T and c.1658G > A, were detected. The frequency of carriers was about 1/28. In patients with HCC, there were only 2 carriers with c.851_854del mutant. Patients with NICCD (n = 5) diagnosed during 2007 and 2008, harbored compound heterozygous mutations c.851_854del/c.1177 + 1G > A, c.851_854del/c.1638_1660dup (n = 2), c.851_854del/c.615 + 5G > A, and c.1638_1660dup/c.615 + 5G > A. Conclusions HRM analysis is a simple, rapid and robust method for detecting SLC25A13 mutations in clinical laboratories. SLC25A13 mutations may not be a major contributor to the pathogenesis of HCC in Taiwan.

The aim of this study was to determine the levels of phthalate ester metabolites in girls in early puberty, and the associated environmental factors for phthalate exposure. A case-control study was conducted in which we recruited girls in early puberty, including 30 girls with premature thelarche (PT) and 26 with central precocious puberty (CPP), and 33 normal controls. The mean urine levels of monomethyl phthalate (MMP) were significantly higher in the PT group (96.5 +/- 134.0 ng/ml) than in the control group (26.4 +/- 30.0 ng/ml; p = 0.005). The levels of monobutyl phthalate (MBuP) correlated with the intake of seafood, drink and the use of plastic cups. The levels of mono-(2-ethylhexyl) phthalate (MEHP) correlated with the intake of seafood and meat and exposure plastic handi-wrap. Significantly higher MMP in the PT girls revealed that phthalate may be one of the environmental causes of early puberty in Taiwanese girls.

This report presents the case of a 7-year-old girl with gonadotrophin-independent precocious puberty treated with cetrorelix [gonadotrophin-releasing hormone (GnRH) antagonist] after poor response to GnRH agonist therapy was observed in the endocrinology outpatient clinic. Uterine and ovarian morphology returned to within the normal prepubertal range after GnRH antagonist was injected subcutaneously. Vaginal bleeding stopped completely. The effects of GnRH antagonist treatment were comparable to those of GnRH agonist. The potential advantage of GnRH antagonists would be a clinically significant direct effect on the ovary, if it exists, and GnRH antagonists should be available for use in such children.

The association of hypophosphatemic rickets and epidermal nevus or giant hairy nevus is rare. We report two patients with hypophosphatemic rickets, one associated with epidermal nevus syndrome and the other with giant hairy nevus, and describe their clinical features and variable response to treatment. The abnormal nevus tissue may have contributed to the pathogenesis of hypophosphatemic rickets. We did not find a PHEX gene mutation in these two patients, and the mechanism for their rickets may be different from that in X-linked hypophosphatemic rickets.

Objectives To promote adolescent health care in Taiwan, we conducted a national questionnaire-based survey to assess experience and training needs in adolescent medicine among pediatricians in Taiwan. Materials and Methods A 13-item questionnaire was mailed to all physicians registered in the Taiwan Pediatric Association. Perceived importance, necessity, skill, and training needs for main adolescent health issues were reported anonymously on a 5-point scale. We also analyzed their experience and competence in management of these adolescent health issues compared with management of two common pediatric diseases, respiratory tract infections and gastrointestinal disease. Data were analyzed using descriptive statistics, the χ 2 test, paired t test, Spearman correlation, and logistic regression analysis. Results A total of 226 questionnaires were included in the final analysis. Pediatricians’ perceived competence in adolescent health problems was lower than that for common pediatric diseases. The analysis showed a positive correlation between competence and experience in medical practice. A higher likelihood of case referral was associated with lower perceived competence. Most respondents rated these adolescent issues “very important” or “important” (60–88%), whereas few of them reported being “very knowledgeable” or “knowledgeable” (11–36%). Nevertheless, most doctors were “very interested” or “interested” (44–71%) in receiving further training. Adolescent health issues related to “obesity, nutrition counseling, and eating disorders;” “growth and development during puberty and endocrine disorders;” and “mental health” were perceived to be of highest importance, whereas the medical topics “obesity, nutrition counseling, and eating disorders;” “dermatologic disorders;” and “growth and development during puberty and endocrine disorders” were considered top priorities for further training. Conclusion Taiwanese pediatricians, perceiving suboptimal experience and competence in managing many adolescent health problems, consistently expressed strong interest in receiving further adolescent medicine training. We identified and prioritized their training needs for a wide variety of adolescent health issues. These findings are expected to help guide the development of integrative educational programs for pediatricians in Taiwan.

Background Mucopolysaccharidosis type II (MPS II) is an X-linked recessive, multisystemic lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase. MPS II has a variable age of onset and variable rate of progression. In Asian countries, there is a relatively higher incidence of MPS II compared to other types of MPS. Methods A retrospective analysis was carried out of 34 Taiwanese MPS II patients who died between 1995 and 2012. The clinical characteristics, medical records, age at death, and cause of death were evaluated to better understand the natural progression of this disease. Results The mean age at death of 31 of the patients with a severe form of the disease with significant cognitive impairment was 13.2 ± 3.2 years, compared with 22.6 ± 4.3 years in the three patients with a mild form of the disease without cognitive involvement (n = 2) or the intermediate form (n = 1) (p