Comparison of 25-hydroxy vitamin D serum levels among children with epilepsy in therapy with single versus multiple antiseizure medications.

Objective: Treatment with antiseizure medications (ASMs) for more than 6 months requires monitoring of side effects, one of which is a decreased level of serum vitamin D. This study aimed to compare the influence of therapies with one versus multiple ASMs on 25-hydroxy vitamin D (25-OHD) levels among children with epilepsy. Methods: Our cross-sectional comparative study was conducted in the Paediatric Neurology Clinic at Soetomo Academic Hospital. Epileptic children aged 2-18 years who had been using ASMs for at least 6 months were enrolled and grouped according to whether they had been taking single or multiple ASMs. The mean 25-OHD levels of both groups were compared using a Welch t-test (95% confidence interval). Results: Among the 60 children enrolled, vitamin D deficiency was identified in 13% of children taking a single ASM and in 53% of ones taking multiple ASMs; mean 25-OHD levels were 26.6 (SD 5.29) ng/mL and 20.2 (SD 4.25) ng/mL, respectively. There was a significant difference between the groups (p = 0.001). Conclusions: Patients taking single and multiple ASMs have lower 25-OHD levels than expected for their age, with those taking multiple ASMs having the lowest 25-OHD levels.

Selenium level correlates negatively with antibodies but positively with thyroid function in children with down syndrome: an Indonesian study.

Background: Children with Down syndrome (DS) are prone to developing autoimmune thyroid disease (AITD). Previous studies found lower selenium (Se) levels in children with AITD. Glutathione peroxidase-3 (GPx3) and selenoprotein-P (SePP) are widely used to measure Se levels. DS children tend to have lower Se levels, the main contributor to hypothyroidism in this population. This study aimed to analyze the Se's role in AITD in Indonesian children with DS. Methods: This cross-sectional study was conducted between February 2021-June 2022 at the Pediatric Outpatient Clinic of Dr Soetomo Hospital. DS children aged 1 month to 18 years were enrolled using consecutive sampling. Thyroid-stimulating hormone, free thyroxine, thyroid peroxidase (TPO-Ab) and thyroglobulin (Tg-Ab) autoantibody, GPx3, and SePP levels were measured in plasma samples using enzyme-linked immunosorbent assays. Statistical analyses used Chi-square, Mann-Whitney, and Spearman's rank correlation (r s). All results with p<0.05 were considered statistically significant. Results: Among 62 children with DS, SePP and GPx3 levels were significantly lower in those with AITD than those without AITD (p=0.013 and p=0.018, respectively). SePP and GPx3 levels correlated significantly with lower TPO-Ab (r s=-0.439 with p=1×10-5 and r s=-0.396 with p=0.001, respectively) and Tg-Ab (r s=-0.474 with p=1×10-5 and r s=-0.410 with p=0.001, respectively) levels. SePP levels correlated significantly with lower thyroid dysfunction incidence (r s=-0.252, p=0.048) in the AITD group. Conclusion: Selenium deficiency contributes to autoimmune process in the thyroid and to thyroid dysfunction in children with Down syndrome. Our findings recommend increasing Se levels through Se-containing foods to reduce the risks of AITD and thyroid dysfunction in DS children with AITD.

The association between PTPN22 C1858T gene polymorphism and type 1 diabetes mellitus: an Indonesian study.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is disease caused by the destruction of ß pancreatic cells. The activation of T-lymphocyte and proliferation inhibitor are induced by protein tyrosine phosphatase non-receptor type 22 (PTPN22). However, the link between PTPN22 C1858T gene polymorphism and T1DM is still controversy. This study aimed to analyse the C1858T gene polymorphism in Indonesian children with T1DM. MATERIALS AND METHODS: This case-control study was conducted from March 2021 to May 2022 in the Endocrinology Outpatient Clinic at Dr. Soetomo Hospital and Tropical Disease Center Universitas Airlangga. Patients with controlled T1DM during the study period were included. The PTPN22 analysis used polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Sixty-two children voluntarily participated in this study, and were equally divided into the T1DM and control groups. Most of the patients (94%, 58/62) are Javanese. This study revealed a more frequent CC genotype (9.4%) and allele-C (54.6%) polymorphism in the T1DM group, while more frequent CT genotype (100%) and allele-T (50%) polymorphism were in the control group. The C- and T-allele frequency was 54.6% and 45.4% in the T1DM group, respectively. The T1DM and control groups did not significantly differ (p= .2381). CONCLUSIONS: PTPN22 homozygous genotype-CC and allele-C polymorphisms are more frequent in patients with T1DM. However, the PTPN22 C1858T gene polymorphism did not significantly correlate to T1DM children in this study.Key Messages:The PTPN22 C1858T gene polymorphism does not significantly affect the susceptibility of T1DM in Indonesian children.PTPN22 homozygous genotype-CC polymorphism was more observed in the T1DM group; thus, this genotype may play as a risk factor for T1DM children in the Indonesian population.

Cytotoxic T-lymphocyte-associated protein 4 +49A/G polymorphism in Down syndrome children with Hashimoto's thyroiditis.

Thyroid dysfunction is the most common endocrine disorder in Down syndrome (DS) children. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is one of the immune regulatory genes that correlates with Hashimoto's thyroiditis (HT). However, studies on CTLA-4 +49A/G in DS children with HT are still limited. We aimed to evaluate CTLA-4 +49A/G gene polymorphism in DS children with HT. This case-control study, conducted from February 2020 to February 2022 at Dr. Soetomo General Hospital, Surabaya, enrolled 40 DS children with HT and 50 healthy children. The DNA sequencing was performed to identify the polymorphism (Sanger sequencing). Thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels were analyzed by enzyme-linked immunosorbent assay (ELISA). The mean age of DS children with HT was 1.78 years. Males predominated in the study population. Subjects with GG genotype were diagnosed earliest with hypothyroidism (8 months) compared with other studies. The most common thyroid dysfunction was central hypothyroidism, with TgAb positivity present in all patients. The AA genotype (odds ratio [OR] 0.265, 95% confidence interval [CI] 0.094-0.746; P = 0.012) and A allele (OR 0.472, 95% CI 0.309-0.721; P = 0.0002) were significantly more frequent in the control group. The AG genotype (OR 2.65, 95% CI 0.094-0.746; P = 0.003) and G allele (OR 2.116, 95% CI 1.386-3.23; P = 0.003) were more frequent in the DS with HT group. The age of the subjects in this study was younger than in previous studies. The AG genotype and the G allele were more prevalent in the DS with HT group and may be a risk factor in HT development in DS children. Furthermore, the AA genotype may act as a protective factor against HT in DS children.

Protein tyrosine phosphatase non-receptor type 22 C1858T gene polymorphism in children with down syndrome and autoimmune thyroid diseases.

Autoimmune Thyroid Disease (AIT) is a frequent comorbidity in Down Syndrome (DS). Protein Tyrosine Phosphatase Non- Receptor Type 22 C1858T (PTPN-22 C1858T) gene polymorphisms have a role in the progression of AIT. The study on PTPN- 22 C1858T gene polymorphism as the risk factor of AIT in DS children is still limited. This study aims to evaluate PTPN-22 C1858T polymorphism in Indonesian DS children. A cross-sectional study involving 31 DS children with hypothyroidism (19 boys/12 girls) was conducted for ten months from February to November 2020 at Dr. Soetomo General Hospital Surabaya. The PTPN-22 C1858T gene polymorphism was analyzed using Polymerase Chain Reaction-Restriction-Fragment-Length Polymorphism (PCR-RFLP). Anti-Thyroid Peroxidase (Anti- TPO) and Anti-Thyroglobulin (Anti-TG), FT4, T3, and TSH levels were analyzed using Enzyme-Linked-Immunosorbent-Assay (ELISA). The mean age of the subjects was 19.45±17.3 months. The CT variant of PTPN-22 C1858T was observed in all subjects. The mean level of T3, FT4, and TSH were 1.59±0.45 ng/mL, 0.81±0.57 ng/mL, 0.22±0.21 µU/mL, respectively. Around 83.9% of patients suffered from central hypothyroidism, 12.9% from primary hypothyroidism, and 3.2% from subclinical hypothyroidism. The positive anti-TG and anti-TPO were observed in 96.8% and 58.1%, respectively. CT variant was observed in Indonesian DS children who suffered from hypothyroidism.

The correlation between vitamin D and levels of IFN-γ, NF-κB, thyroid antibodies in down syndrome: study in Indonesian children.

BACKGROUND AND AIM: Vitamin D (VD) reduces interferon-gamma (IFN-γ) production and prevents nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, impacting the inhibition of the autoimmunity process such as autoimmune thyroiditis (AITD). Children with Down syndrome (DS) are reported to have a higher risk of autoimmunity and lower VD levels than non-DS. Therefore, this study aimed to evaluate VD levels in Indonesian DS children and their relationship with marker of AITD. METHODS: This study was conducted on DS children at Dr Soetomo Hospital between February 2021-June 2022. Socio-demographic status, amount of milk, fish and meat consumption, and duration of sun exposure were obtained using a self-report questionnaire. Thyroid hormone (TSH and FT4), thyroid antibody (TPO-Ab and Tg-Ab), 25 (OH)D, IFN-γ, and NF-κB levels were measured using ELISA. RESULTS: Of the 80 participants, 53.75% had sufficient (50.829±17.713 ng/ml) and 46.25% had non-sufficient (20.606±5.974 ng/ml) VD levels. Daily milk consumption, meat and fish consumption were risk factors contributing to VD levels in multivariate analysis [p=0.003, OR=1.007(1.003-1.012); p=0.004, OR=1.816(1.209- 2.728), respectively]. Participants with sufficient VD had significantly higher TPO-Ab (p=0.007) and Tg-Ab (p=0.016). Mean of VD levels were significantly negatively correlated with IFN-γ levels (r =-0.262, p=0.037) and positively correlated with TPO-Ab (r= 0.432, p=1x10-5,) and Tg-Ab (r= 0.375, p=0.001). CONCLUSIONS: Majority of subjects had sufficient VD levels. VD suppresses IFN-g, but is unable to affect NF-κB levels, presumably causing high levels of TPO-Ab and Tg-Ab in sufficient VD patient.

CTLA-4 CT-60 A/G and CTLA-4 1822 C/T Gene Polymorphisms in Indonesians with Type 1 Diabetes Mellitus.

Introduction: CTLA-4 gene polymorphism plays an important role in children with type 1 diabetes mellitus (T1DM). However, data on this subject vary among different races and ethnics. Purpose: To analyze CTLA-4 CT-60 A/G and CTLA-4 1822 C/T gene polymorphism among children with T1DM compared to control. Patients and Methods: The CTLA-4 CT-60 A/G and CTLA-4 1822 C/T gene polymorphism in children with T1DM using polymerase chain reaction-restriction fragment length polymorphism in 25 T1DM and 25 controls. The inclusion criteria were patients regularly controlled at the Pediatric Endocrine Outpatient Clinic of Dr. Soetomo Hospital, aged 4-18 years and willing to join this study and the exclusion criteria were T1DM patients hospitalized in the pediatric intensive care unit. In the control group, the inclusion criteria were healthy children, aged 4-18 years and willing to join this study. The exclusion criteria included children with ongoing infection, history of other autoimmune diseases, allergies, or malignancy. Results: The mean age was 12.48 years old, and the mean of T1DM onset was 9.28 years old. The CTLA-4 1822 T allele observed in 62% T1DM and 56% in control (p = 0.388, OR = 0.78, 95% CI = 0.44-1.37) and CTLA-4 CT-60 G allele observed in 52% T1DM and 58% in control (p = 0.393, OR = 1.27, 95% CI = 0.73-2.22). The C/T genotypes was significantly higher in control group (p = 0.045, OR = 3.27, 95% CI = 1.00-10.62). The A/G genotypes was commonly found in control group (p = 0.765, OR = 1.20, 95% CI = 0.37-3.86). The Javanese was the dominant ethnic group in our study. Conclusion: The frequency of CTLA-4 CT-60 A/G polymorphism almost equivalent in T1DM and control group. However, CTLA-4 1822 C/T polymorphism was more prevalent in the control group; thus, this genotype may have a protective effect against T1DM.

HLA-DQA1 and HLA-DQB1 Gene Polymorphism in Indonesian Children with Type I Diabetes Mellitus.

BACKGROUND: More than 40 genes influence the progression of type 1 diabetes mellitus (T1DM), including human leukocyte antigen (HLA) alleles. Different HLA genotype patterns result in diverse rates of T1DM development. HLA class II DR, DQ, and DP vary among different populations and ethnicities. Data on HLA polymorphism in T1DM in Indonesia are lacking. Therefore, this study was designed to evaluate the gene polymorphism of HLA-DQA1 and HLA-DQB1 in Indonesian children with T1DM. PATIENTS AND METHODS: In this study, 31 patients with T1DM and 31 controls were enrolled from April 2020 to April 2021. This study was conducted at Dr. Soetomo Hospital, Indonesia. We evaluated the gene polymorphism of HLA-DQA1 and HLA-DQB1 using polymerase chain reaction-restriction fragment length polymorphism. The primers used were as follows: for HLA-DQA1, DQAS34: 5'-GGTGTAAACTTGTACCAG-3' (forward) and DQAA261: 5'-ATTGGTAGCAGCGGTAGA-3' (reverse); for HLA-DQB1, DQBS43: 5'-TGCTACT- TCACCAA(C/T)GGG-3' (forward) and DQBA249: 5'-GTAGTTGTGTCTGCA (C/T)AC-3' (reverse). RESULTS: The most common HLA-DQA1 subtype in the T1DM group was 0101/0102 accounting for 67.6%, and 01/03 and 02/03 were found in the T1DM group only. Meanwhile, the most common HLA-DQB1 subtype in the T1DM group was 0301, accounting for 54.8%. Most subjects in this study were Javanese. CONCLUSION: HLA-DQA1 0101/0102 and HLA-DQB1 0301 were commonly found in Indonesian children with T1DM.

Quality of Life Differences in Pre- and Post-Educational Treatment in Type 1 Diabetes Mellitus During COVID-19.

PURPOSE: The coronavirus-19 (COVID-19) pandemic requires the use of online media to ensure monitoring of type 1 diabetes mellitus (T1DM) in children. Thus, this study aims to determine whether online education effectively improves the quality of life (QoL) in children with T1DM during the coronavirus-19 pandemic. PATIENTS AND METHODS: The study, conducted from March to October 2020, utilized the paired t-test before and after online education. Moreover, it adopts the recommended Pediatric Quality of Life Inventory (PedsQL) 3.2 diabetes module for the 33 patients registered in the Pediatric Endocrine Outpatient Clinic of Dr. Soetomo Hospital, Surabaya, Indonesia. RESULTS: The QoL of all children (p = 0.011), parents (p = 0.001), and both children and parents (overall; p = 0.002) have shown significant improvement after the treatment. The QoL of parents, as a subcriterion, improved after the treatment. However, the improvement in the children in subcriterion treatment II (p = 0.186) was not significant. CONCLUSION: Online education has proven to create a better QoL almost in all children with T1DM during the coronavirus-19 pandemic.

Zinc transporter 8 autoantibody in the diagnosis of type 1 diabetes in children.

BACKGROUND: Type 1 diabetes (T1D) is an organ-specific autoimmune disease related to the autoimmune response against pancreatic ß-cells. Zinc transporter 8 (ZnT8), an islet-specific gene product localized to the ß-cell insulin granule, was recently identified as an autoantigen in T1D. PURPOSE: To evaluate the use of ZnT8 autoantibody (ZnT8A) for diagnosing T1D. METHODS: This case-control study was conducted at Dr. Soetomo General Hospital, Surabaya, Indonesia, from March to May 2019. Children younger than 18 years of age with T1D based on the International Society for Pediatric and Adolescent Diabetes guideline and healthy controls were included. We measured ZnT8A level using enzyme-linked immunosorbent assay (cutoff value, 0.315). RESULTS: There were 30 children with T1D (50.0% boys; mean age, 11.3±3.7 years) and 18 healthy controls (44.4% boys; mean age, 8.3±3.1 years); 1 patient in each group was Madurese, while the others were Javanese. Twenty-two of 30 subjects with T1D (73.3%) tested positive for ZnT8A compared to 5 of 18 controls (27.8%) (P=0.02; odds ratio, 7.15; 95% confidence interval, 1.93-26.52). When ZnT8A-positive and -negative T1D cases were compared, no differences were detected in age at diagnosis, duration of diabetes, presence of ketoacidosis, body mass index, glycosylated hemoglobin concentration, or C-peptide concentrations. CONCLUSION: ZnT8A may be useful in the diagnosis of T1D.