OBJECTIVE—To study the effect of birth weight on risk of type 2 diabetes in the schoolchildren in Taiwan. RESEARCH DESIGN AND METHODS—From 1992 to 1997, all schoolchildren aged 6–18 years were screened for diabetes in Taiwan Province. This cohort consisted of 1,966 patients with diabetes and 1,780 randomly selected subjects with normal fasting glycemia (NFG). Questionnaire interviewing was designed to classify diabetes. The birth weight was obtained from the Taiwan’s Birth Registry. After merging the data, there were 978 subjects, including 429 with type 2 diabetes and 549 with of NFG enrolled in the present analyses. RESULTS—The odds ratios (95% CI) for type 2 diabetes, after adjusting age, sex, BMI, family history of diabetes, and socioeconomic status, were 2.91 (1.25–6.76) for children with low birth weight (<2,500 g) and 1.78 (1.04–3.06) for those with high birth weight (≥4,000 g) when compared with the referent group (birth weight 3,000–3,499 g). The risk of diabetes was still 64% higher in the high birth weight group [odds ratio (OR) 1.64 (95% CI 0.91–2.96)], even after adjustment for gestational diabetes mellitus (GDM). Patients with type 2 diabetes who were born with high birth weight were more likely to have a higher BMI and diastolic blood pressure as well as a higher family history of diabetes compared with those with low birth weight. CONCLUSIONS—A U-shaped relationship between birth weight and risk of type 2 diabetes was found in the schoolchildren aged 6–18 years in Taiwan. Schoolchildren with type 2 diabetes who were born with low birth weight had different metabolic phenotypes compared with those born with high birth weight.

Context Despite a disturbing trend of increasing prevalence of type 2 diabetes mellitus (DM) in childhood, little is known about the epidemiology of childhood type 2 DM, especially in the Taiwanese population.Objective To study the rate and risk factors for childhood type 2 DM based on a nationwide screening program in Taiwan.Design, Setting, and Participants Screening in 1999 for type 2 DM using urine and blood testing and confirmed by follow-up telephone survey among schoolchildren aged 6 to 18 years in Taiwan, followed by a nested case-control study conducted in 2002 comparing 137 children with type 2 DM with 1000 randomly selected children without diabetes chosen to represent the age and sex distribution of the whole student population.Main Outcome Measures Rate and identification of risk factors associated with childhood type 2 DM. ResultsThe rate of newly identified diabetes was 9.0 per 100000 for boys and 15.3 per 100000 for girls. Follow-up at 3 years revealed that, of 253 children with newly diagnosed diabetes, 24 (9.5%) had type 1 DM, 137 (54.2%) had type 2 DM, and 22 (8.7%) had secondary diabetes. Compared with children aged 6 to 9 years, the odds ratios (ORs) and 95% confidence intervals (CIs) of type 2 DM increased to 6.59 (3.23-13.4) for those aged 13 to 15 years and to 4.59 (2.07-10.2) for those aged 16 to 18 years. The OR (95% CI) of type 2 DM in children with a body mass index in the 95th percentile or higher (obesity) was 18.8 (9.22-38.5) compared with those with a body mass index in less than the 50th percentile. Other factors significantly associated with type 2 DM were hypercholesterolemia (OR, 1.80; 95% CI, 1.04-3.23), blood pressure greater than the 85th percentile (OR, 1.70; 95% CI, 1.07-2.70), and positive family history of diabetes (OR, 3.95; 95% CI, 2.01-7.78). ConclusionsOur mass screening program showed that type 2 DM is the leading cause of childhood DM in Taiwan. Obesity is a major risk factor for the development of type 2 DM in children.

In Taiwan, during the period March 2000 to June 2009, 1,495,132 neonates were screened for phenylketonuria (PKU) and homocystinuria (HCU), and 1,321,123 neonates were screened for maple syrup urine disease (MSUD), methylmalonic academia (MMA), medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) deficiency, isovaleric academia (IVA), and glutaric aciduria type 1 (GA-1) using tandem mass spectrometry (MS/MS). In a pilot study, 592,717 neonates were screened for citrullinemia, 3-methylcrotonyl-CoA carboxylase deficiency (3-MCC) and other fatty acid oxidation defects in the MS/MS newborn screening. A total of 170 newborns and four mothers were confirmed to have inborn errors of metabolism. The overall incidence was approximately 1/5,882 (1/6,219 without mothers). The most common inborn errors were defects of phenylalanine metabolism [five classic PKU, 20 mild PKU, 40 mild hyperphenylalaninemia (HPA), and 13 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency]. MSUD was the second most common amino acidopathy and, significantly, most MSUD patients (10/13) belonged to the Austronesian aboriginal tribes of southern Taiwan. The most frequently detected among organic acid disorders was 3-MCC deficiency (14 newborns and four mothers). GA-1 and MMA were the second most common organic acid disorders (13 and 13 newborns, respectively). In fatty acid disorders, five carnitine transport defect (CTD), five short-chain acyl-CoA dehydrogenase deficiency (SCAD), and two medium-chain acyl-CoA dehydrogenase (MCAD) deficiency were confirmed. This is the largest case of MS/MS newborn screening in an East-Asian population to date. We hereby report the incidences and outcomes of metabolic inborn error diseases found in our nationwide MS/MS newborn screening program.

The aim of this study was to: (a) analyze the results of a large-scale newborn screening program for Pompe disease, and (b) establish an effective diagnostic protocol to obtain immediate, valid diagnosis of infantile-onset Pompe disease (IOPD) to promote earlier treatment and better outcomes. In this study, 402,281 newborns were screened for Pompe disease from January 1, 2008 to May 1, 2012. Infants with low acid α-glucosidase (GAA) activity were referred to Taipei Veterans General Hospital for diagnostic confirmation. Physical examination, biochemical parameter (creatine kinase [CK], alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase), and echocardiogram assessments were performed immediately to effectively differentiate IOPD from suspected late-onset Pompe disease (LOPD) or false-positive cases with pseudodeficiency mutation. Six infants with IOPD all presented with hypotonia, extremely low GAA enzyme activity (≤0.5 µmol/L/hr) in initial dried blood spot analysis, high CK (≥250 U/L), and high left ventricular mass index (LVMI, ≥80 g/m(2)). By analyzing these parameters, IOPD was distinguished effectively and immediately from suspected LOPD and false-positive cases. Except for the first referred case, five of the infants with IOPD received first-time enzyme replacement therapy (ERT) within 4 hr of admission and exhibited marked improvement. Our findings indicate that certain clinical manifestations (hypotonia, high CK, enlarged LVMI, and extremely low GAA enzyme activity in initial dried blood spot analysis) can help in the rapid and effective differentiation of patients with IOPD from other patient with low GAA activity. Such differentiation allows for the early application of first-time ERT and leads to better outcomes.

BackgroundMucopolysaccharidoses (MPS) are lysosomal storage diseases in which mutations of genes encoding for lysosomal enzymes cause defects in the degradation of glycosaminoglycans (GAGs). The accumulation of GAGs in lysosomes results in cellular dysfunction and clinical abnormalities. The early initiation of enzyme replacement therapy (ERT) can slow or prevent the development of severe clinical manifestations. MPS I and II newborn screening has been available in Taiwan since August 2015. Infants who failed the recheck at recall were referred to MacKay Memorial Hospital for a detailed confirmatory diagnosis.MethodsFrom August 2015 to November 2017, 294,196 and 153,032 infants were screened using tandem mass spectrometry for MPS I and MPS II, respectively. Of these infants, 84 suspected cases (eight for MPS I; 76 for MPS II) were referred for confirmation. Urinary first-line biochemistry examinations were performed first, including urinary GAG quantification, two-dimensional electrophoresis, and tandem mass spectrometry assay for predominant disaccharides derived from GAGs. If the results were positive, a confirmative diagnosis was made according to the results of leukocyte enzymatic assay and molecular DNA analysis. Leukocyte pellets were isolated from EDTA blood and used for fluorescent α-iduronidase (IDUA) or iduronate-2-sulfatase (IDS) enzymatic assay. DNA sequencing analysis was also performed.ResultsNormal IDS and IDUA enzyme activities were found in most of the referred cases except for four who were strongly suspected of having MPS I and three who were strongly suspected of having MPS II. Of these infants, three with novel mutations of the IDS gene (c.817C > T, c.1025A > G, and c.311A > T) and four with two missense mutations of the IDUA gene (C.300-3C > G, c.1874A > C; c.1037 T > G, c.1091C > T) showed significant deficiencies in IDS and IDUA enzyme activities (< 5% of mean normal activity), respectively. Urinary dermatan sulfate and heparan sulfate quantitative analyses by tandem mass spectrometry also demonstrated significant elevations. The prevalence rates of MPS I and MPS II in Taiwan were 1.35 and 1.96 per 100,000 live births, respectively.ConclusionsThe early initiation of ERT for MPS can result in better clinical outcomes. An early confirmatory diagnosis increases the probability of receiving appropriate medical care such as ERT quickly enough to avoid irreversible manifestations. All high risk infants identified in this study so far remain asymptomatic and are presumed to be affected with the attenuated disease variants.