Factors affecting the health-related quality of life of children with cerebral palsy in Indonesia: a cross-sectional study.

PURPOSE: Children with cerebral palsy (CP) and their parents experience various problems that can affect their quality of life. This study examined factors affecting the quality of life of children with CP. METHODS: A cross-sectional study was conducted in Yogyakarta, Indonesia, from January to August 2019. The participants were consecutively recruited children with CP aged 2 to 18 years and their parents. Ninety-eight children with CP and their parents, specifically their mothers, were recruited. Children's health-related quality of life (HRQoL) was measured using the Pediatrics Quality of Life Cerebral Palsy. Parental HRQoL and stress were measured using the WHOQOL-BREF and Parenting Stress Index (PSI). RESULTS: Functional level V was the most common category for both Gross Motor Function Classification System (GMFCS) and Bimanual Fine Motor Function (BFMF) (35% and 28%, respectively). Children's mean HRQoL was medium (49.81±20.35). The mean total PSI score was high (94.93±17.02), and 64% of parents experienced severe stress. Bivariate analysis showed that GMFCS, BFMF, number of comorbidities, presence of pain, and parental stress were significantly correlated with the total score for children's HRQoL (p<.05). Multiple linear regression analysis (p<.05) demonstrated that more severe GMFCS and parental stress were associated with lower mean HRQoL scores in children. CONCLUSION: Factors including the level of GMFCS and parental stress affected the HRQoL of children with CP. Parental stress management should be included in the comprehensive management of these children.

Dp71 and intellectual disability in Indonesian patients with Duchenne muscular dystrophy.

INTRODUCTIONS: Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive muscular disease marked by developmental delays due to mutations in the DMD gene, which encodes dystrophin. Brain comorbidity adds to the burden of limited mobility and significantly impacts patients' quality of life and their family. The changes of expression of dystrophin isoforms in the brain due to DMD gene mutations are thought to be related to the cognitive and neurobehavior profiles of DMD. OBJECTIVES: This cross-sectional study aimed to characterize cognitive and neurodevelopmental profiles of patients with DMD and to explore underlying genotype-phenotype associations. METHODS: Patients with DMD aged 5-18 years from Dr Sardjito Hospital and Universitas Gadjah Mada Academic Hospital from 2017-2022 were included. Multiplex ligation-dependent probe amplification and whole exome sequencing were used to determine mutations in the DMD genes. Cognitive function was measured by intelligence quotient testing using the Wechsler Intelligence Scale for Children and adaptive function tests with Vineland Adaptive Behavior Scales. The Autism Mental Status Exam and Abbreviated Conner's Rating Scale were used to screen for autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD), respectively. RESULTS: The mean total IQ score of DMD patients was lower than that of the general population (80.6 ± 22.0 vs 100 ± 15), with intellectual disability observed in 15 boys (29.4%). Of the 51 patients with DMD, the Dp71 group had the lowest cognitive performance with a total IQ score (46 ± 24.8; p = 0.003), while the Dp427 group and Dp140 group's total IQ scores were 83.0 ± 24.6 and 84.2 ± 17.5 respectively. There were no DMD patients with ASD, while 4 boys (7.8%) had comorbidity with ADHD. CONCLUSION: Boys with DMD are at higher risk of intellectual disability. The risk appears to increase with mutations at the 3' end of the gene (Dp71 disruption). Moreover, Dp71 disruption might not be associated with ADHD and ASD in patients with DMD.

Prevalence and associated factors of psychosocial and behavioral problems in Indonesian adolescent students during the COVID-19 pandemic.

Background: The COVID-19 pandemic and the subsequent measures to control it, such as social distancing, school closure, and online learning, put adolescent students at higher risk of psychosocial and behavioral problems (PSBP). The adverse potential is more concerning as the outbreak continues, especially in limited-resource countries, and requires further mitigation. Objective: To assess the prevalence and factors associated with PSBP in Indonesian adolescent students in the COVID-19 pandemic. Subject/methods: We conducted a cross-sectional study in Yogyakarta Province, Indonesia, involving junior high school students. An anonymous online questionnaire in google form format was used to collect demographic data and the potential variables and screen the PSBP with the Strengths and Difficulties Questionnaire (SDQ). Logistic regression was applied to determine the independent variables. Results: Six hundred seventy-six subjects participated, including 237 males (35.1%) and 439 females (64.9%). There were 34.6% subjects with PSBP, with a peer-relation problem as the most common one. The multivariable logistic regression showed that subjects with longer screen time duration and more family conflicts were more likely to have PSBP, with an adjusted odds ratio (OR) of 1.5 (95% CI: 1.1-2.1, p = 0.025) and 2.4 (95% CI: 1.5-3.8, p < 0.001), respectively, whereas whom with better family cohesion are less likely to have the problem with an adjusted OR of 0.4 (95% CI: 0.3-0.6, p < 0.001). Conclusions: There is a high prevalence of PSBP among Indonesian adolescent students during the COVID-19 pandemic. Longer screen time duration and more family conflict are associated with higher prevalence, whereas better family cohesion with lower prevalence of PSBP.

Indonesian mothers' beliefs on caring practices at home for preterm babies after hospital discharge: A qualitative study.

PURPOSE: Premature birth may be associated with infant health problems and frequently requires in-hospital and then at-home specialized care. Studies investigating home-caring experiences of mothers of preterm infants in developing countries are limited. This study was to explore preterm mothers' experiences of caring practices at home 1 month after their infant's discharge from a neonatal unit. DESIGN AND METHOD: A descriptive qualitative study using in-depth interviews with eight purposively sampled mothers who had been discharged home from neonatal unit in one city in Indonesia. All interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. RESULT: Three main themes emerged: (1) transition to independent motherhood, (2) focus on care of infant after discharge, and (3) barriers and enablers for care. The mothers managed their infant care at home by focusing on feeding and managing infant health problems. They faced on myth and culture as one of the barriers. CONCLUSIONS: Comprehensive discharge education for mothers of preterm infants and their families is required to enhance mothers' caring abilities and overcome barriers is sufficient. Nurses/midwives need to improve care related to the well-being of mothers and their infants in preparation for, and after, discharge from the neonatal unit.

Translation, Adaptation and Psychometric Validation of the Indonesian Version of the Readiness for Hospital Discharge Scale for Parents of Low Birth Weight Infants.

PURPOSE: Parental readiness is a requirement for discharge of the high-risk infant from the hospital. Currently, in Indonesia, there are no standard tools to measure parental readiness according to parents' perceptions. This study aimed to undertake cross-cultural adaptation and psychometric validation of the original version (English) of the Readiness for Hospital Discharge Scale (RHDS)-Parent into Bahasa Indonesia. DESIGN AND METHODS: The cross-cultural adaptation was comprised of seven steps: forward translation, forward translation review, blind-back translation, back translation review, pilot testing of the pre-final version with mothers of low birth weight (LBW) infants, expert panel for conceptual and content equivalence, and initial psychometric testing. In the fifth and sixth steps, content validity index was estimated. In the seventh step, exploratory factor analysis (EFA) and internal consistency reliability were conducted. In total, 146 mothers of LBW infants were included in the psychometric testing using convenience sampling. RESULTS: The 22 item Bahasa-RHDS-Parent emerged in a four-factor structure evident from EFA. This version has good reliability with Cronbach alpha values for knowledge and coping ability (0.92), physical-emotional readiness (0.89), pain and power (0.83), expected support (0.80) and 0.90 across the total Bahasa-RHDS-Parent. CONCLUSION: The Bahasa-RHDS-Parent presents good cross-cultural adaptation and initial psychometric properties for assessing parental readiness in parents with LBW infants before hospital discharge. PRACTICE IMPLICATIONS: This questionnaire can be used by nurses to measure readiness for discharge of parents of low birthweight babies. Further testing is needed with a larger sample and parents of children of other ages and conditions for instrument improvement.

Switch from oral to inactivated poliovirus vaccine in Yogyakarta Province, Indonesia: summary of coverage, immunity, and environmental surveillance.

BACKGROUND: Inactivated poliovirus vaccine (IPV) is rarely used in tropical developing countries. To generate additional scientific information, especially on the possible emergence of vaccine-derived polioviruses (VDPVs) in an IPV-only environment, we initiated an IPV introduction project in Yogyakarta, an Indonesian province. In this report, we present the coverage, immunity, and VDPV surveillance results. METHODS: In Yogyakarta, we established environmental surveillance starting in 2004; and conducted routine immunization coverage and seroprevalence surveys before and after a September 2007 switch from oral poliovirus vaccine (OPV) to IPV, using standard coverage and serosurvey methods. Rates and types of polioviruses found in sewage samples were analyzed, and all poliovirus isolates after the switch were sequenced. RESULTS: Vaccination coverage (>95%) and immunity (approximately 100%) did not change substantially before and after the IPV switch. No VDPVs were detected. Before the switch, 58% of environmental samples contained Sabin poliovirus; starting 6 weeks after the switch, Sabin polioviruses were rarely isolated, and if they were, genetic sequencing suggested recent introductions. CONCLUSIONS: This project demonstrated that under almost ideal conditions (good hygiene, maintenance of universally high IPV coverage, and corresponding high immunity against polioviruses), no emergence and circulation of VDPV could be detected in a tropical developing country setting.

A novel mutation at the N-terminal of SMN Tudor domain inhibits its interaction with target proteins.

Although most patients with spinal muscular atrophy (SMA) are homozygous for deletion of the SMN1 gene, some patients bear one SMN1 copy with a subtle mutation. Detection of such an intragenic mutation may be helpful not only in confirming diagnosis but also in elucidating functional domains of the SMN protein. In this study, we identified a novel mutation in SMN1 of two Japanese patients with type I SMA. DHPLC and sequencing analysis revealed that they harbored a point mutation in SMN1 exon 3, 275G > C, leading to tryptophan-to-serine substitution at amino acid 92 (W92S) at the Nterminal of SMN Tudor domain. In-vitro protein binding assays showed that the mutation severely reduced interaction of the domain with SmB protein and fibrillarin, suggesting that it impairs the critical function of SMN. In conclusion, we reported here that a novel mutation, W92S, in the Tudor domain affects the interaction of SMN with the target proteins.

Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry.

Mutations in the gene encoding UDP-glucuronosyltransferase 1A1 (UGT1A1) may reduce the glucuronidation of estradiol, bilirubin, etc. In the present study, we used a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to assay the activities of recombinant mutated UGT1A1 toward 17beta-estradiol (E2), by determining its glucuronide (E2G) content. Direct evidence for glucuronide formation was provided by E2G-specific ion peaks. The UGT1A1 activities of G71R (exon 1), F83L (exon 1), I322V (exon 2) and G493R (exon 5) mutants were 24, 30, 18 and 0.6% of the normal UGT1A1 activity, respectively. In conclusion, our study showed that LC/MS/MS enabled accurate evaluation of the effects of mutations on recombinant UGT1A1 activity towards E2.

Screening for G71R mutation of the UGT1A1 gene in the Javanese-Indonesian and Malay-Malaysian populations.

BACKGROUND: There are significant differences in the prevalence and severity of neonatal jaundice among various populations. Recently, it has been reported that a mutation of the UGT1A1 gene, glycine to arginine at codon 71 (G71R), is related to the development of neonatal jaundice in East Asian populations. However, whether the G71R mutation contributes to the high incidence of neonatal jaundice in different Asian populations remains unknown. The authors screened for this mutation in the Javanese-Indonesian and Malay-Malaysian populations. METHODS: One hundred and thirty-six subjects were enrolled in this study: 68 Javanese-Indonesian adults and 68 Malay-Malaysian newborns (32 with jaundice and 36 without jaundice). Denaturing high-performance liquid chromatography (DHPLC) was used to screen for the G71R mutation, and the results were confirmed by nucleotide sequencing analysis. RESULTS: With DHPLC, the authors easily and clearly detected seven subjects carrying the G71R mutation: two Javanese-Indonesian adults and five Malay-Malaysian newborns. In the 68 Javanese-Indonesian adults, the genotype distribution for G71R mutation was 66 G/G, two G/R and no R/R genotypes, and the mutated allele frequency was 0.015. In the 68 Malay-Malaysian newborns, genotype distribution for the mutation was 63 G/G, five G/R and no R/R genotypes, and the mutated allele frequency was 0.037. The genotype distributions did not differ significantly between the newborns with jaundice and those without jaundice. CONCLUSION: The G71R mutation is present, but very rare, in Javanese-Indonesians and Malay-Malaysians. Thus, G71R mutation may not contribute to the high incidence of the neonatal jaundice in South-east Asian populations. DHPLC analysis is a very useful method for detecting the G71R mutation.

C677T mutation in the MTHFR gene was not found in patients with frontoethmoidal encephalocele in East Java, Indonesia.

BACKGROUND: Frontoethmoidal encephalocele (FEE) is a neural tube defect (NTD) characterized by a congenital bone defect in the anterior cranium and herniation of the intracranial mass through the defect. The C677T mutation in the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) has been reported as a genetic risk factor for spina bifida. However, the role of the MTHFR in the pathogenesis of FEE remains to be clarified. METHODS: A hospital-based survey of FEE patients who were referred to the Department of Neurosurgery and Plastic Surgery, Malang General Hospital, East Java, Indonesia was conducted. Genetic screening of MTHFR substitutions in 13 patients and eight mothers from 11 affected families were performed using a combination of polymerase chain reaction (PCR), denaturing high-performance liquid chromatography (DHPLC), and direct sequencing. RESULTS: In total, 130 patients with FEE among 138 NTD patients (94.2%) were identified. The ratios of cranial encephalomeningocele to spinal meningocele (32 : 1) and of FEE to occipital encephalomeningocele (32 : 1) were higher than those in other populations. Five substitutions were detected in the MTHFR: C121T, C677T, C1060T, A1298C, and G1793A. No significant differences were found in the frequency of each nucleotide substitution between patients or mothers and controls. In addition, none of the subjects in this study were homozygous for T at nucleotide position 677. CONCLUSION: FEE is the most common form of NTD in East Java, Indonesia. Genetic analysis of 11 affected families suggests that the MTHFR gene is not associated with the development of FEE, although the number of FEE families analyzed in this study was very limited.

Deletion of the SMN1 and NAIP genes in Vietnamese patients with spinal muscular atrophy.

The SMN1 and NAIP genes are related to the development of spinal muscular atrophy (SMA), which is characterized by degeneration of motor neurons leading to progressive muscular weakness and atrophy. The SMN1 gene is homozygously deleted in most SMA patients, and now recognized as a responsible gene for SMA. The NAIP gene is often deleted in the SMA patients with the severest form of SMA, and now considered to be a modifying factor of the severity of SMA. Our previous study of five Vietnamese SMA patients showed that the SMN1 gene deletion was detected in one patient, although the NAIP gene deletion was not detected in any patients. In this study, we analyzed 12 Vietnamese SMA patients who were not enrolled in the previous study. The SMN1 gene was homozygously deleted in six out of 12 patients, and the NAIP gene deletion was detected in five patients. Taken together with our previous data, the SMN1 gene deletion was detected in seven out of 17 Vietnamese SMA patients and the NAIP gene deletion in five out of 17 Vietnamese SMA patients. These studies suggest that the SMN1 and NAIP gene deletions are not rare in Vietnamese SMA patients. Thus, the confirmation of SMA-related gene deletion will also be a useful tool for the diagnosis of SMA in Vietnam.

Correlation between SMN2 copy number and clinical phenotype of spinal muscular atrophy: three SMN2 copies fail to rescue some patients from the disease severity.

Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder that is characterized by degeneration of the anterior horn cells of the spinal cord, which leads to the axial and limb weakness associated with muscle atrophy. SMA is classified into three groups based on the clinical severity: type I (severe), type II (intermediate) and type III (mild). All three clinical subtypes of SMA are caused by mutations of the SMN1 gene. More than 95 % of SMA patients show homozygous deletion of SMN1. It is thought that SMN2, which is a highly homologous gene of SMN1, compensates for the SMN1 deletion to some degree. To clarify the relationship between SMN2 and the disease severity of SMA, we performed fluorescence-based quantitative polymerase chain reaction assay of the copy number of SMN2 in 27 patients (11 type I and 16 type II-III) homozygous for SMN1 deletion. The SMN2 copy number in type II-III patients was 3.1 +/- 0.3 (mean +/- SD), which is significantly higher than that observed in type I patients, 2.2 +/- 0.6 (P < 0.01). However, three of the 11 type I patients carried 3 SMN2 copies. A type I patient with 3 SMN2 copies was studied further. RT-PCR analysis of the patient showed a trace of full-length SMN2 mRNA species, but a large amount of the truncated SMN2 mRNA species lacking exon 7. In conclusion, SMN2 alleles are not functionally equivalent among SMA patients, although in general the SMN2 copy number is correlated with the severity of SMA. Genetic background influencing splicing mechanisms of the SMN2 gene may be more critical in some SMA patients.

No relationship exists between itai-itai disease and TA repeat polymorphisms of the estrogen receptor alpha gene.

Itai-itai (ouch-ouch) disease is a syndrome accompanied by bone mineral disorders that may be related to oral cadmium exposure. Itai-itai predominantly affects postmenopausal women with a history of multiple childbirth. In a previous study we have examined the genotype distributions of PvuII and XbaI restriction fragment length polymorphisms of the estrogen receptor alpha (ER alpha) gene in patients with itai-itai disease and compared them with those of controls. However, no significant differences were shown between the genotype distributions of the patients and controls. In the present study, we determined the TA repeat polymorphisms of the patients and controls. The distributions of the patients were: HH 25.0%, HL 50.0%, and LL 25.0%; where HH includes two alleles with a high number of TA repeats (TA> or =16), HL includes one high number allele and one low number allele (TA< or =15), and LL includes two alleles with a low number of TA repeats. These patients' distributions were not significantly different from those of the controls. Although our sample number was limited, we concluded that a polymorphism variant of the ER alpha gene is not a predisposing factor for itai-itai disease.

Novel missense mutation of the UGT1A1 gene in Thai siblings with Gilbert's syndrome.

BACKGROUND: Gilbert's syndrome is a common inherited disorder of bilirubin metabolism contributing to the development of neonatal jaundice and causing recurrent jaundice after the neonatal period. In the patients with Gilbert's syndrome, mutations have been reported in the promoter and exons of the uridine diphosphate-glucuronosyl transferase 1 (UGT1A1) gene on chromsome 2q37, which encodes bilirubin uridine diphosphate-glucuronosyltransferase. However, the genetic basis of Gilbert's syndrome, including its inheritance trait, remains to be clarified. METHODS: Patients 1 and 2 were Thai sisters with Gilbert's syndrome. They had a history of prolonged neonatal jaundice and showed recurrent jaundice after their infancy, while the parents showed no symptoms. To search for the mutation in the patients, all exons of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and sequenced directly. The frequency of the mutation in controls was studied by PCR-restriction enzyme digestion method. RESULTS: The patients were homozygous for a novel single transition of T to C at nucleotide position 247 (exon 1), which would predict a substitution of leucine for phenylalanine at codon 83 of the enzyme protein. No other mutation was detected in any regions except exon 1. The parents with no symptoms showed heterozygosity for the mutation. Among the 110 Japanese controls, no homozygous individuals and three heterozygous individuals for the mutation were identified, giving a mutated allele frequency of 0.0136. CONCLUSIONS: A novel missense mutation in the UGT1A1 gene was identified in two Thai siblings with Gilbert's syndrome. The affected family showed that homozygosity for the mutation may lead to apparent symptoms and that the syndrome was inherited as an autosomal recessive trait. The mutation does not explain a high incidence of neonatal jaundice in Japan, because it is very rare in the Japanese population.

The C677T mutation in the methylenetetrahydrofolate reductase gene among the Indonesian Javanese population.

The presence of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene has been regarded as a genetic risk factor for coronary artery diseases and neural tube defects. Although the prevalence of this mutation has been reported from various ethnic populations, few data concerning Indonesian populations are available. We have investigated the frequency of the mutation in 68 Indonesian Javanese (residents of Java Island) and compared it with the data from 244 Japanese (residents of Honshu Island). The frequencies of the three genotypes in Javanese were C/C 0.84, C/T 0.16 and T/T 0.00, whereas those in Japanese were C/C 0.39, C/T 0.48 and T/T 0.13. The rarity of the T/T genotype in the Indonesian Javanese population may be due to malnutrition in pregnant women, because insufficient intake of folate is considered to be a survival disadvantage for fetuses with the T/T genotype. In conclusion, homozygosity for the C677T mutation in the MTHFR gene does not constitute a genetic risk factor for coronary artery diseases and neural tube defects in the Indonesian Javanese population.