Self-efficacy affects blood sugar control among adolescents with type I diabetes mellitus.

BACKGROUND/PURPOSE: Self-management is crucial to diabetes control. To investigate the effectiveness of self-management in reaching target hemoglobin A1c (HbA1c) level, we conducted a study among Taiwanese adolescents with type 1 diabetes mellitus (DM). METHODS: Patients aged 12-20 years with type 1 DM participated in an annual integrated DM care clinic at a medical center in Taiwan. All patients completed a questionnaire that included demographic data and self-efficacy measured by the Perceived Diabetes Self-Management Scale (PDSMS) in February 2008. Laboratory tests were also done at the same visit. The target HbA1c was < 7.0% in accordance with the general standard of the American Diabetes Association for patients with type 1 DM. Logistic regression analysis was used to explore the relationship between age, sex, duration of diabetes, PDSMS score, and HbA1c level. RESULTS: Fifty-two patients were enrolled. The mean age was 16.0 +/- 2.4 years, and mean HbA1c level was 8.6 +/- 1.6%. Pearson correlation analysis showed a positive correlation between body mass index and preprandial blood sugar level (r = 0.297, p < 0.05). Negative correlations were found between PDSMS scores and duration of diabetes (r = -0.365, p < 0.01) as well as HbA1c level (r = -0.295, p < 0.05). Logistic regression analysis demonstrated that sex and PDSMS scores significantly influenced glycemic control. In multivariate logistic regression analysis, patients with higher PDSMS scores were 1.63 times (95% confidence interval = 1.03-2.59) more likely to reach target diabetes control after adjustment for other variables. Male patients also had a higher probability (odds ratio = 19.80, 95% confidence interval = 1.34-291.93) of reaching target diabetes control. CONCLUSION: This study demonstrates that adolescents with type 1 DM and higher self-efficacy, especially males, have a higher probability of reaching target diabetes control.

The gene founder effect of two spontaneous mutations in ethnic Chinese (Taiwanese) CAH patients with 21-hydroxylase deficiency.

CYP21A2 mutations resulting from microconversions of the CYP21A1P sequence in congenital adrenal hyperplasia (CAH) commonly appear in all populations. However, it has not often been described as being due to the gene founder effect. Herein, we investigated two spontaneous mutations of IVS2+1G>A and R316X in ethnic Chinese (Taiwanese) CAH patients to determine whether they share the same haplotype of ancient origin by the analysis of sequence-specific oligonucleotide (SSO) for HLA class I B and sequence-based typing (SBT) for HLA class II DRB1 gene-typing methods. From over 200 CAH families, eight unrelated CAH patients were found and examined: five had the IVS2+1G>A mutation and three had the R316X mutation. Based on HLA typing data, five alleles in five patients with the IVS2+1G>A mutation were consistent with a shared haplotype of the B *3909-DRB1 *160201 allele, and the three alleles in the three patients with the R316X mutation were all the B *460101-DRB1 *080302 allele. The evidence indicates that the haplotype of single-base substitutions of either the IVS2+1G>A or R316X mutation came from the same allele rather than a mutational hot spot, suggesting that the gene founder effect has occurred in the Taiwanese population. This is the first report of the gene founder effect of the CYP21A2 mutation occurring in ethnic Chinese (Taiwanese) CAH patients with 21-hydroxylase deficiency.

Noonan syndrome caused by germline KRAS mutation in Taiwan: report of two patients and a review of the literature.

Noonan syndrome is a highly variable disorder that has significant phenotypic overlap with Costello syndrome and cardio-facio-cutaneous syndrome. KRAS mutation was the second reported gene for Noonan syndrome. This study screened for mutation of the KRAS gene in 57 unrelated ethnic Chinese children suffering from Noonan syndrome without PTPN11 gene mutation in Taiwan. This work only identified two patients with different missense mutations (c.40G>A, p.Val14Ile; c.108A>G, p.Ile36Met) in the exon 1 of KRAS gene. This study also analyzed the characteristics of 34 reported cases involving KRAS mutations in the literature. All these patients presented with variable phenotypes, including Noonan syndrome (n = 19), cardio-facio-cutaneous syndrome (n = 7), Costello syndrome (n = 6), and Noonan/cardio-facio-cutaneous syndrome (n = 1). The phenotype of KRAS mutations was generally severe, including short stature, mental retardation, heart defects, etc. In conclusion, this investigation demonstrates that KRAS mutations are the cause in a minority of cases of Chinese patients with Noonan syndrome in Taiwan.

Early development in Williams syndrome.

BACKGROUND: The aim of the present study was to gain a better understanding of the motor performance in Williams syndrome for early intervention of rehabilitation programs. METHODS: Eleven Williams syndrome patients were evaluated from the pediatric clinics. Seven patients younger than 42 months were evaluated with the Bayley II Test for mental development index (MDI) and psychomotor development index (PDI). Four patients older than 42 months were evaluated with the Bruininks-Oseretsky Test (short form) of motor profile. The raw scores were measured and converted to the standard scores for comparison. RESULTS: A significantly mental and psychomotor development delay of 6.1 and 5.7 months individually was found compared to that of the mean age (P > 0.0047 and 0.0053). Juvenile Williams syndrome patients were apparently retarded (<10 per thousand rank) in motor development in comparison with persons of the same age. The results showed that motor performance was severely delayed not only in Williams syndrome children but also in Williams syndrome juveniles. CONCLUSION: It is important for clinicians to work out a comprehensive plan to help the motor development of patients with Williams syndrome in addition to treating their medical problems, and upper limb dexterity may be the goal for training.

Anthropometric and intellectual evaluation of individuals with Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a rare, multifaceted genetic disorder resulting from the absence of normally active paternally expressed genes from the 15q11-q13 chromosome region. Due to a lack of anthropometric and intellectual data in Taiwan, we attempted these evaluations. Twenty patients (14 males/6 females) aged 7-23 years with molecularly confirmed PWS were enrolled with parental consent. Their mean height standard deviation score (SDS) was -1.26 +/- 1.89 (from -4.3 to +2.16); mean weight SDS was +1.77 +/- 2.00 (from -0.44 to +5.89); mean body mass index SDS was +3.84 +/- 10.54 (from -0.08 to +10.48); and mean body fat tissue SDS was 39.4 +/- 10.54% (14.7-57.8%) by an InBody 3.0 analyzer. All were hypogonadal. Nine of them had once been given growth hormone therapy, and were taller and slimmer than the rest. Their intelligence tests showed full intelligence quotient = 52.0 +/- 7.6; verbal intelligence quotient = 55.9 +/- 8.77; performance intelligence quotient = 53.2 +/- 9.0. Chronic health status revealed that diabetes was prevalent among the older population. Their IQ was in the range of those with moderate retardation.

Bone mineral density and correlation factor analysis in normal Taiwanese children.

BACKGROUND: Our aim was to establish reference data and linear regression equations for lumbar bone mineral density (BMD) in normal Taiwanese children. Several influencing factors of lumbar BMD were investigated. METHODS: Two hundred fifty-seven healthy children were recruited from schools, 136 boys and 121 girls, aged 4-18 years were enrolled on a voluntary basis with written consent. Their height, weight, blood pressure, puberty stage, bone age and lumbar BMD (L2-4) by dual energy x-ray absorptiometry (DEXA) were measured. Data were analyzed using Pearson correlation and stepwise regression tests. RESULTS: All measurements increased with age. Prior to age 8, there was no gender difference. Parameters such as height, weight, and bone age (BA) in girls surpassed boys between ages 8-13 without statistical significance (p> or =0.05). This was reversed subsequently after age 14 in height (p<0.05). BMD difference had the same trend but was not statistically significant either. The influencing power of puberty stage and bone age over BMD was almost equal to or higher than that of height and weight. All the other factors correlated with BMD to variable powers. Multiple linear regression equations for boys and girls were formulated. CONCLUSIONS: BMD reference data is provided and can be used to monitor childhood pathological conditions. However, BMD in those with abnormal bone age or pubertal development could need modifications to ensure accuracy.

Seventeen alpha-hydroxylase deficiency.

Seventeen alpha-hydroxylase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia in which defects in the biosynthesis of cortisol and sex steroid result in mineralocorticoid excess, hypokalemic hypertension and sexual abnormalities such as pseudohermaphroditism in males, and sexual infantilism in females. The disease is inherited in an autosomal recessive pattern, and is caused by mutations in the gene encoding cytochrome P450c17 (CYP17), which is the single polypeptide that mediates both 17alpha-hydroxylase and 17,20-lyase activities. We report the case of a 15-year-old patient with 17OHD who had a female phenotype but male karyotype (46,XY). The diagnosis was made based on classical clinical features, biochemical data and molecular genetic study. Two mutations were identified by polymerase chain reaction amplification and sequencing, including a S106P point mutation in exon 2 and a 9-bp (GACTCTTTC) deletion from nucleotide position 1519 in exon 8 of CYP17. The first of these mutations was found in the father and the second in the mother, and both have been previously reported in Asia. The patient's hypertension and hypokalemia resolved after glucocorticoid replacement and treatment with potassium-sparing diuretics. Sex hormone replacement was prescribed for induction of sexual development and reduction of the final height. Prophylactic gonadectomy was scheduled. In summary, 17OHD should be suspected in patients with hypokalemic hypertension and lack of secondary sexual development so that appropriate therapy can be implemented.

Pseudohypoparathyroidism: report of seven cases.

Pseudohypoparathyroidism (PHP) is a rare inherited syndrome with several types. We reviewed the cases of 7 PHP patients seen between 1990 and 2003, and analyzed their clinical, biochemical data and long-term medical outcomes. Six boys and one girl were included. Two siblings showed Albright's hereditary osteodystrophy (AHO) and PHP Ia was impressed. The rest were suspected of PHP Ib. Their mean diagnosed age was 10.8 years and most had symptoms onset for several years before diagnosis. The most frequent initial presentations were seizure, followed by extremity muscle spasm, short stature, learning disability and psychomotor retardation. Mild thyrotropin elevation was noted in two patients of PHPIa. Early puberty onset, combined with bone age advancement was noted in the boy with PHP Ia, who had the shortest predicted adult height (PAH) (139.5 cm). The other 5 boys had normal PAH, mean 171.42 cm, and 4 male patients reached final height with a mean of 163.25 cm, close to their target heights. During treatment, 2 patients developed nephrocalcinosis. In conclusion, subtypes of PHP present heterogeneous phenotypes. Non-Ia subtypes might not be rare in Taiwan. Therefore, in hypocalcemic patients with mild high or normal parathyroid hormone (PTH), even in the absence of AHO, PHP should be ruled out. Regular renal sonography follow-up is recommended during therapy.

Maple syrup urine disease in the Austronesian aboriginal tribe Paiwan of Taiwan: a novel DBT (E2) gene 4.7 kb founder deletion caused by a nonhomologous recombination between LINE-1 and Alu and the carrier-frequency determination.

Maple syrup urine disease (MSUD) is an autosomal recessive inborn error disorder derived from the accumulation of the branched-chain amino acids (BCAAs) leucine, isoleucine and valine. Either the E1alpha, E1beta or DBT (E2) genes are responsible for this neurometabolic disease. Here, we report the identification and characterization of a novel E2 gene 4.7 kb deletion as a rare nonhomologous recombination of the long interspersed nuclear elements 1 (LINE-1) in intron 10 and the Alu in the 3' UTR of the E2 gene from three classic MSUD patients of the Austronesian aboriginal tribe Paiwan in Taiwan. The E2 gene 4.7 kb deletion accounted for five out of six alleles in the three unrelated Paiwanese MSUD patients, indicating a founder effect. Carrier-frequency study revealed one deleted heterozygote out of 101 normal Paiwanese. As the nine Taiwanese Austronesian aboriginal tribes share a common origin, this E2 4.7 kb deletion may be preserved in some of the other Austronesian aboriginal tribes of Taiwan. This is the first comprehensive genetics study of MSUD in the Austronesian tribal groups as well as in Taiwan.

Wolfram syndrome: phenotype and novel mutation in two Taiwanese siblings.

Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder. The responsible gene, WFS1, was identified in 1998 and over 66 mutations have been reported since then. We report 2 siblings in a Taiwanese family with WS. They had similar clinical courses, including successive development of diabetes mellitus, optic atrophy, diabetes insipidus, hearing impairment, and urological complications from age 5 to 15 years. Rapid progression of systemic and neurological symptoms was noted in the elder brother. Mutation analysis of the 2 probands revealed compound heterozygotes of 1 novel and 1 previously reported mutation. Their parents and an asymptomatic sibling were carriers of 1 mutation.

A mucolipidosis III patient presenting characteristic sonographic and magnetic resonance imaging findings of claw hand deformity.

Mucolipidosis III (ML-III), or pseudo-Hurler polydystrophy, is an autosomal recessive Hurler-like disorder without mucopolysacchariduria. The diagnosis is challenging for rheumatologists since the musculoskeletal presentation is similar to some rheumatic diseases. We report a case of ML-III in a 16-year-old Taiwanese boy. The characteristic findings of sonography and magnetic resonance imaging (MRI) of claw hand deformity are described. A 16-year-old boy was referred to our rheumatologic clinic because of progressive claw hand deformity, multiple joint stiffness and tightness of the skin over the fingers at the age of 6 years. Sonography and MRI examination disclosed tendon sheath thickening over extensor tendons of both wrists and fingers without features of active inflammation over tendons or joints nor thickening of skin. Urinary glycosaminoglycans were normal. The diagnosis of ML-III was confirmed by the presence of elevated activities of beta-glucuronidase (2141.99 nmol/mg protein/hour), arylsulfatase A (1237.7 nmol/mg protein/hour) and alpha-fucosidase (52.95 nmol/mg protein/hour) in his plasma and decreased activity of these lysosomal enzymes in cultured skin fibroblasts. Sonography and MRI screening for claw hand deformity may offer important clues enabling early diagnosis of ML-III.

Type I glutaric aciduria: phenotypes and genotypes in 5 Taiwanese children.

We describe the clinical characteristics of 5 Taiwanese children with glutaric aciduria type I treated in a single medical center. Macrocephaly was present in 5 of these patients, psychomotor retardation in 4, and neurological regression in 2. Diagnosis was made prenatally in 1 patient due to an affected sibling. Low lysine/tryptophan formula, carnitine, and vitamin B2 were given to all patients. All patients disliked and could not adhere to the special formula and medications. Four older patients had neurological deficits prior to the start of the regimen. Among them, 1 died of sepsis and malnutrition. Only the prenatally diagnosed child did well at age 22 months. Mutational analysis, performed by polymerase chain reaction and sequencing, revealed an IVS10-2A>C defect in all 5 patients, and 2 siblings were homozygous. In addition, 2 novel mutations were detected. We conclude that GA I might not be as rare in Taiwan as previously thought. IVS10-2A>C is a common mutation in the Taiwanese population, whose genotypes are quite different from those of Caucasians.

Detection of novel CFTR mutations in Taiwanese cystic fibrosis patients.

BACKGROUND AND PURPOSE: Cystic fibrosis (CF) in Asian populations is very rare. We performed molecular genetic analysis in 2 Taiwanese CF patients for detection of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. METHODS: Temporal temperature gradient gel electrophoresis (TTGE) was used for mutation detection, and direct sequencing was used for identification of mutations. RESULTS: In one patient, 2 novel mutations, E7X and 989-992insA, were identified and the carrier status of his parents was confirmed. In the other patient, 3 mutations, S895N, 2215insG, and 1898+5G>T, were found. The 2215insG and S895N were found cis in the same chromosome. These splice site, frameshift, and nonsense mutations produce severely truncated CFTR polypeptides which lack a transmembrane domain, nucleotide binding folds, and the regulatory region, and are predicted to be null in CFTR function. CONCLUSIONS: These cases underscore the importance of comprehensive mutation analysis of Taiwanese CF patients. Definitive molecular findings can confirm the clinical diagnosis and facilitate patient management, carrier testing, and genetic counseling. Furthermore, there is an urgent need to understand the mutation spectrum and the clinical features of the CFTR gene in Asian patients in order that a mutation panel can be established for effective screening of CF chromosomes.

Unstratified chemotherapy for non-metastatic osteosarcoma of the extremities in children.

BACKGROUND AND PURPOSE: The superiority of changing postoperative chemotherapy of osteosarcoma based on histological response of the primary tumor over non-tailored chemotherapy has not been confirmed. This multicenter study evaluated the effectiveness of an intensive unstratified chemotherapy regimen in Taiwanese children with osteosarcoma. METHODS: Fifty patients younger than 18 years of age with previously untreated non-metastatic osteosarcoma of the extremities were enrolled. Patients were treated with pre- and postoperative chemotherapy, and surgery. Definitive surgery was scheduled in week 7 and postoperative chemotherapy was uniform without stratification regardless of histologic response. RESULTS: Chemotherapy toxicities were considerable, but manageable. Treatment delay and decreased dose-intensity were common. There was one treatment-related mortality. Forty three patients (86%) received limb salvage surgery and 14 patients (33%) had a good histologic response to preoperative chemotherapy. With a median follow-up of 47.1 months, the 7-year event-free and overall survival rates were 51.6% and 67.6%, respectively. CONCLUSIONS: This was the first multicenter study on the treatment of osteosarcoma from Taiwan. The results suggest that a non-tailored regimen may serve as an alternative treatment strategy in the management of osteosarcoma, particularly when histologic assessment of the tumor response is not available.

Epidemiology, clinical features and treatment outcome of Wilms' tumor in Taiwan: a report from Taiwan Pediatric Oncology Group.

BACKGROUND AND PURPOSE: Taiwan Pediatric Oncology Group (TPOG)-W-91 is the first multi-institutional Wilms' tumor study for children in Taiwan. This clinical trial used a multidisciplinary approach, based on and similar to the National Wilms' Tumor Study 4. The study was conducted to evaluate the epidemiological characteristics and analyze the outcome of Wilms' tumor patients treated with this protocol. METHODS: Ninety eight children with Wilms' tumor (WT) were analyzed for distributions of age, gender, associated congenital anomalies, tumor sites, histology, tumor weights, and clinical stages. Patients received individualized multimodality treatment based upon the histology of the tumor and clinicopathologic stage. The treatment included surgery, radiotherapy and 2-, 3-, and 4-agent active chemotherapeutic agents. Seventy patients were eligible for analysis of treatment outcome. The endpoints were progression-free and overall survival (PFS, OS). Patients were divided into various subgroups according to the chemotherapy regimen used, tumor stage, age at diagnosis, gender, and tumor weight. The prognostic factors were evaluated and the survival rates of various clinical subgroups were compared using log-rank test. RESULTS: The average annual incidence rate of WT was 2.9 per million children under 15 years of age. The M/F ratio was 1.04. The mean age at diagnosis was 3.7 years. All bilateral tumors occurred in females. Congenital anomalies were present in 17.3% of patients. Anaplastic histology was found in 6 of 98 cases (6.1%). The stage distribution was: I, 43.2%; II, 19.3%; III, 23.9%; IV, 6.8%; and V, 6.8%. The median follow-up time was 89.1 months (range, 1.8 to 128.1 months). The 5-year PFS rate was 0.7841 (SE, 0.0494; 53 of 70 patients) and the 5-year OS rate was 0.886 (SE, 0.038; 63 of 70 patients). Gender was found to be the only significant prognostic variable. CONCLUSIONS: This study evaluated the epidemiological characteristics, clinical features, multimodality therapy regimens, and treatment outcome of WT in Taiwan. Data obtained from this study may lead to further improvement in the prognosis of pediatric malignant solid tumor.

Spondyloepiphyseal dysplasia tarda: report of one case.

We report the clinical assessment and mutational analysis of one boy with spondyloepiphyseal dysplasia tarda (SEDT). His short stature manifested between age 5 and 10. As his growth slowed, his height fell from the mean for his age at 5 to the 2nd percentile at age 10.5. His bone age was retarded at 8 years, thus his predicted adult height was 164.9 cm, not far from his target height of 170cm. However, upon physical examination, he presented markedly short trunk. We suspected SEDT and X-ray finding of his spine supported this diagnosis. We performed DNA analysis on the SEDL gene and detected a 5-bp deletion in exon 5 which has been previously reported by Mumm et al. and Gedeon et al. in cases of SEDT.

Clinical evaluation of short children referred by school screening: an analysis of 655 children.

A national screening and referral program of short school children was launched in Taiwan in 2000. We analyzed 655 referrals (boys 303, girls 352) from this program whose heights were below--2 standard deviation score (SDS) for age and gender. Evaluation included: detailed medical history, physical examination and laboratory tests such as blood count, thyroid function, growth hormone screening, bone age and chromosome tests. The results were compared with worldwide data. Normal variations accounted for 64.9% of all etiologies for reasons such as constitutional delay 37.4%, familial short stature 16.5%, and a combination of above two 11.0%. The rest were of pathological short stature for reasons such as: idiopathic short stature 7.9%, growth hormone deficiency 7.9%, precocity 3.2%, skeletal dysplasia 2.3%, intrauterine growth retardation 1.4%, Turner syndrome 1.4%, other chromosomal anomaly 0.8%, and others 5.0%. We conclude that the majority of short stature in Taiwanese children is due to normal variation although potentially treatable causes account for at least 12.8% of cases, such as GHD, Turner syndrome, hypothyroidism and precocity. The inexpensive screening program therefore seems to be beneficial in identifying children with short stature of potentially treatable etiology.

Outcome of antithyroid medication and radioiodine therapy in pediatric Graves' disease.

Graves' disease is a significant medical condition in children. The optimal therapy is controversial. We reviewed 40 pediatric patients with Graves' disease, 5.0-17.7 yrs of age (mean 10.2 yrs), treated for at least one yr from 1990 to 2002 to assess the outcome of antithyroid medication and radioiodine therapy. The follow-up duration was 1.1-11.8 yrs (mean 5.1 yrs). Clinical variables were also analyzed to identify the prognostic factors. The 40 patients were divided into 3 groups according to their therapeutic options to analyze outcome. To identify predictors, patients who achieved remission after antithyroid drugs within 2 yrs (n = 7) were compared with those who received more than 2 yrs of medication but did not enter remission (n = 25). In group 1, 28 patients received antithyroid drugs for 0.7-10 yrs (mean 3.4 yrs). Fourteen (50%) achieved remission after 0.7-6.6 yrs (mean 2.6 yrs). In group 2, 9 patients received subsequent radioiodine therapy (10-15 mCi) after antithyroid drugs for 1.1-9.2 yrs (mean 4.4 yrs). Remission was achieved after 1-11 months (mean 3.1 months) in 8 (89%). In group 3, initial 131I (12-15 mCi) was used in 3 patients. All of them (100%) attained remission within 2 months. The overall remission rate of patients receiving medical therapy (group 1 and 2) was 38% (14/37). Of the 11 patients who achieved remission after radioiodine, 10 had hypothyroid status and required thyroxine replacement. There were no significant differences with any of the clinical variables that might predict remission after medication within 2 yrs, possibly because of the small number of patients. Our data demonstrate that radioiodine is an efficient and effective therapy for pediatric Graves' disease as first-line treatment or subsequent therapy for those with relapsed disease after medical therapy, although most patients develop hypothyroidism after treatment.

Characteristics of hospitalizations among adolescents in Taiwan: population-based data.

To understand the adolescent health status in Taiwan, we collected hospitalization data of Taiwanese adolescents in 1997 under the execution of National Health Insurance (NHI). Then 5% of the data was selected with systematic sampling method by National Health Research Institute (NHRI) and was categorized according to age, gender, disease pattern and specialty. The results showed there were totally 160, 120 adolescent admissions in 1997, about 6.81% of total population admissions. There were more female than male admissions and more late adolescent than early adolescent admissions. In clinical disorders, injury was the leading cause of hospitalization for male adolescent and female early adolescent admissions. Delivery was the leading cause of hospitalization for female late adolescent admissions. The most common specialty admissions among early adolescents were for pediatrics, followed by surgery, and then general medicine. Among late adolescents, the most common specialty admissions were for surgery, followed by obstetrics and gynecology, and then general medicine. In conclusion, the most common reasons of adolescence hospitalization were related to behavioral factors rather than disease processes, and adolescent admissions by specialty were mostly non-professional.