Agustini Utari

Side Effects of Minocycline Treatment in Patients With Fragile X Syndrome and Exploration of Outcome Measures

Minocycline can rescue the dendritic spine and synaptic structural abnormalities in the fragile X knock-out mouse. This is a review and preliminary survey to document side effects and potential outcome measures for minocycline use in the treatment of individuals with fragile X syndrome. We surveyed 50 patients with fragile X syndrome who received minocycline for at least 2 weeks and found that the most common reported side effect is gastrointestinal difficulty, including loss of appetite. The families reported an improvement in language and behavioral areas. Outcome measures in the design of future randomized clinical trials should include both behavioral and language measures. As with any other treatments, we emphasize that randomized clinical trials are needed to determine the efficacy of minocycline in fragile X syndrome.

Clinical involvement in daughters of men with fragile X-associated tremor ataxia syndrome

Chonchaiya W, Nguyen DV, Au J, Campos L, Berry‐Kravis EM, Lohse K, Mu Y, Utari A, Hervey C, Wang L, Sorensen P, Cook K, Gane L, Tassone F, Hagerman RJ. Clinical involvement in daughters of men with fragile X‐associated tremor ataxia syndrome.

Broad Clinical Involvement in a Family Affected by the Fragile X Premutation

The mutations in the FMR1 gene have been described as a family of disorders called fragile X-associated disorders including fragile X syndrome, fragile X-associated tremor/ataxia syndrome, primary ovarian insufficiency, and other problems associated with the premutation, such as hypothyroidism, hypertension, neuropathy, anxiety, depression, attention-deficit hyperactivity disorders, and autism spectrum disorders. The premutation is relatively common in the general population affecting 1 of 130 to 250 female individuals and 1 of 250 to 800 male individuals. Therefore, to provide appropriate treatment and genetic counseling for all of the carriers and affected individuals in a family, a detailed family history that reviews many of the disorders that are related to both the premutation and the full mutation should be carried out as exemplified in these cases. To facilitate the integration of this knowledge into clinical practice, this is the first case report that demonstrates only premutation involvement across 3 generations.

The role of uncoupling protein 2 and 3 genes polymorphism and energy expenditure in obese Indonesian children.

Abstract Aim: Uncoupling protein (UCP) genes, which may contribute to energy metabolism in mitochondria, may be involved in the pathogenesis of obesity. We analyzed the differences in energy expenditure between single nucleotide polymorphisms (SNPs) UCP3-55C/T, UCP3 Y210Y, and UCP2 A55V among Indonesian children. Methods: The study included 76 schoolchildren (36 obese and 40 healthy; mean age, 12.8 years) in Semarang, Indonesia. Body composition was measured by bioelectrical impedance analysis; resting energy expenditure (REE) by indirect calorimetry; physical activity by uniaxial accelerometer; and total energy expenditure (TEE) by the equations extrapolated from REE and physical activity. UCP3-55C/T, UCP3 Y210Y, and UCP2 A55V were examined by restriction length fragment polymorphism analysis. Results: The TEE of the subjects with the T/T genotype at UCP3-55C/T after adjusting for fat-free mass (63.2±7.2 kcal/kg/day) and T/T at UCP2 A55V (62.8±5.6 kcal/kg/day) was lower than that of the subjects with the C/C and C/T genotypes (p<0.05). The REE of the subjects with these T/T genotypes tended to be lower than that of the subjects with C/C and C/T (p≥0.05). No significant differences in REE or TEE were found between the UCP3 Y210Y genotypes. Conclusions: The subjects with the T/T genotypes of UCP3-55C/T or UCP2 A55V had lower TEE than those with other genotypes.

Identification of Expanded Alleles of the FMR1 Gene Among High-Risk Population in Indonesia by Using Blood Spot Screening

The prevalence of Fragile X Syndrome (FXS) is 1 in 4000 in males and 1 in 2500 in males and females, respectively, in the general population. Several screening studies aimed at determining the prevalence of FXS have been conducted in individuals with intellectual disabilities (IDs) with a prevalence varying from 1.15% to 6.3% across different ethnic groups. A previous study in Indonesia showed an FXS prevalence of 1.9% among the ID population. A rapid, effective, and inexpensive method for FMR1 screening, using dried blood spots capable of detecting an expanded FMR1 allele in both males and females, was recently reported. We used this approach to screen 176 blood spots, collected from Central Java, Indonesia, for the presence of expanded FMR1 gene alleles. Samples were collected from high-risk populations: 112 individuals with ID, 32 obtained from individuals with diagnosis of autism spectrum disorders, and 32 individuals with a known family history of FXS. Fourteen subjects carrying an FMR1 expanded allele were identified including 7 premutations (55-200 CGG repeats) and 7 full mutations (>200 repeats). Of the seven subjects identified with a full mutation, one subject was from a non-fragile X family, and six from were families with a history of FXS.

Fragile X syndrome: clinical, cytogenetic and molecular screening among autism spectrum disorder children in Indonesia

Fragile X testing is a priority in the evaluation of autism spectrum disorders (ASD) cases because identification of the FMR1 mutation leads to new treatment options. This study is focused on determining the prevalence of the FMR1 gene mutation among ASD cases in Indonesia. DSM‐IV‐TR criteria were administered to diagnose ASD; symptom severity was classified using the Childhood Autism Rating Scale. Cytogenetic analysis, polymerase chain reaction, and Southern blot for FMR1 gene analysis were carried out to confirm the diagnosis of fragile X syndrome. The fragile X site and FMR1 full mutation allele were identified in 3 out of 65 (4.6%) and 4 out of 65 (6.15%) children aged 3–17 years (57 boys and 8 girls), respectively. The Fragile X laboratory workup is essential in the evaluation of patients with ASD. Molecular analysis is most accurate, while cytogenetic documentation of the fragile X site can also be useful if molecular testing is not available.

Pesticide Exposure and Thyroid Function in Elementary School Children Living in an Agricultural Area, Brebes District, Indonesia

Background: Children living in agricultural areas are at risk of exposure to pesticides due to their involvement in agricultural activities. Pesticides are one of the chemicals classified as endocrine disrupting chemicals. Objective: To examine the association between exposure to organophosphate pesticides and the occurrence of thyroid dysfunction in children. Methods: This cross-sectional study was conducted on 66 children in two elementary schools located in an agricultural area in Brebes District, Indonesia, in 2015. To determine the pesticide exposure history, we analyzed urine samples and completed a questionnaire. Meanwhile, thyroid function tests were performed. Results: Organophosphate pesticide metabolites were detected in urine samples of 15 (23%) of 66 children. Thyroid stimulating hormone (TSH) levels >4.5 μIU/mL were detected in 24 (36%) children. Free thyroxine (FT4) levels of all participants were normal. The mean TSH level in children with positive urinary organophosphate pesticide metabolites (7.74 µIU/mL) was significantly (p=0.005) higher than that in those who were negative (4.34 µIU/mL). The prevalence of hypothyroidism in children with positive urinary organophosphate pesticide metabolites (67%) was significantly higher than that in those who were negative (27%; PR 2.4, 95% CI 1.4 to 4.3). Conclusion: A history of pesticide exposure could be used as a risk factor for the occurrence of thyroid dysfunction in children living in agricultural areas.

Phenotypic Variation of 46,XX Late Identified Congenital Adrenal Hyperplasia among Indonesians

Objectives To describe the phenotype variation in Indonesian 46,XX late-identified congenital adrenal hyperplasia (CAH) and the correlation between 17-hydroxyprogesterone (17-OHP) and genital virilization. Methodology Retrospective study of 39 cases with five salt-wasting (SW) and 34 simple virilizing (SV) types. Results The median age of the patients was 9.83 years (range, 0.58 to 44 years) with Prader score 2 to 5. Clitoromegaly (100%) and skin hyperpigmentation (87%) were the most common features. Lack of breast development (Tanner 1 to 2) and menstrual disorders occurred in 9 patients (teenagers and adults). Short stature (6), low voice (14), prominent Adam’s apple (9) and hirsutism (4) were found only in SV types. Rapid growth (7) and precocious puberty (8) were identified in children. Male gender on admission was found in 13 patients. The mean of 17-OHP level was 304.23 nmol/L [standard deviation (SD) 125.03 nmol/L]. There was no correlation between 17-OHP levels and virilization (r=0.19, p>0.05). Conclusion Late-identified CAH showed severe virilization and irreversible sequelae, with clitoromegaly and skin hyperpigmentation as the most commonly seen features. Masculinization of CAH females created uncertainty with regard to sex assignment at birth, resulting in female, male and undecided genders. There is no significant correlation between 17-OHP levels with the degree of virilization in CAH females.

Adolescents’ Anxiety in the Coastal Region of Central Java, Indonesia

Background: Emotional problems are commonly reported among children, adolescents, and adults. It is known that emotional problems in children who are not treated properly can continue to cause disorder in adolescence and adulthood. This study aimed to investigate anxiety on adolescents, particularly high school and undergrad-uate students, and to compare different subscales of anxiety across educational level. Method: A total of 378 adolescents (286 high school students and 99 undergraduate students; Mage = 16.75; SD = 1.547) participated in this study. Data were collected using the Indonesian version of the Screen for Child Anxiety Disorders (SCARED; 26 items; = .880). Total score and subscale scores were compared between high school students with under-graduate students. Results: The results of independent samples t-test showed that anxiety disorder and panic disorder/school avoidance were more frequently reported by undergraduate students than high school students. However, no significant differences were found in view of generalized anxiety disorder (GAD) and social anxiety. Conclusion: The study findings indicate different profile of anxiety reported by students in the higher level of education that warrant earlyIP: prevention182.255.and1.5interventionOn:Wed,program02Maytailored2018to03:25:39theeducational setting. Awareness on early referral of anxiety problemsCopyright:amongAmericanstudentsshouldScientificberaisedPublishersamongschool principals as well as dean faculties prior to the escalated emotional problemsDelivered.ThebystudyIngentafindings also recommend the need to design a psycho-educational program to reduce anxiety on the undergraduate as well as high school students. Keywords: Anxiety, Adolescents, Emotional Problems, Undergraduate, High School, Students, Coastal Region

Sociocultural aspects of disorders of sex development

Disorders of sex development (DSD) is a congenital condition in which the development of chromosomes, gonads, hormones, and reproductive structures are atypical. DSD brings with it a psychological impact on the affected individual and their families. The consensus statement on management of DSD strongly advised an integrated and multidisciplinary approach in providing care to the affected individuals. Studies have been conducted focusing on medical intervention, and more recently, there is increasing attention paid to psychological aspects of DSD. However, studies reporting cultural aspects of DSD are lacking. This review provides an overview on how culture impacts the affected individuals in coping with DSD and making decisions with regard to gender assignment or reassignment, help-seeking behavior for medical treatments, attitudes toward medical treatment, religious beliefs, and values concerning marriage and fertility. The involvement of social scientists is needed to study sociocultural aspects of DSD from more diverse cultures, to help affected individuals and their families in gaining better social acceptance. Birth Defects Research (Part C) 108:380-383, 2016.