Enzyme Replacement Therapy for Lysosomal Storage Disease in Indonesia

Sjarif, Damayanti Rusli,Hafifah, Cut Nurul Association for Research of MPS and Rare Diseases 2018 Journal of mucopolysaccharidosis and rare disease Vol.4 No.1

Rare diseases are life threatening or chronically debilitating diseases with a low prevalence (less than 2,000 people in a population), which includes lysosomal storage diseases. These diseases are often seen as unimportant especially in developing countries, such as Indonesia, due to small number of patients. National Rare Disease Center in Indonesia was pioneered almost 20 years ago and officially established in 2017 by the Indonesian Minister of Health. Lysosomal storage disease become the most commonly found inborn errors of metabolism (IEM) in Indonesia due to easily accessible diagnostic facilities. Currently there are 7 patients receiving ERT in this mixed-donation scheme, one patient with Gaucher disease and 6 patients with MPS type II. Few challenges for ERT in Indonesia include importation through special access scheme, preparation of ERT infusion in intensive care settting, and cost of treatment. Even with limited resources, healthcare professionals in Indonesia have been giving the best care possible for rare disease patients, especially to provide diagnostic facilities through collaboration and treatment options for treatable rare diseases. Improvements in care for rare disease patients are still needed.

Regurgitation and Gastroesophageal Reflux Disease in Six to Nine Months Old Indonesian Infants

Hegar, Badriul,Satari, Debora Hindra I.,Sjarif, Damayanti R.,Vandenplas, Yvan The Korean Society of Pediatric Gastroenterology 2013 Pediatric gastroenterology, hepatology & nutrition Vol.16 No.4

Purpose: Regurgitation is known to peak at the age of 3-4 months, with a sharp decrease around the age of 6 months. Little is known about the natural evolution of infants who still regurgitate after the age of 6 months. Methods: Hundred thirty-one infants older than 6 months regurgitating more than once a day were followed for a period of 3 months. Results: According to our data, gastroesophageal reflux disease (GERD) is seldom at this age. Most of the infants regurgitated 3 or more times/day and spit up an estimated volume of more than 15 mL. Eighty-five parents were educated regarding frequency of feeding. There were only 6 infants that still had frequent regurgitation (>3 times/day) despite an appropriate feeding schedule. The Infant GER Questionnaire score reached a score of 0 in 50% of the infants after one month of follow-up and in 81.9% at the third month of follow-up. There was an increase of the "weight for age z-score" trends in infants that still regurgitated at the end of follow-up and a declining z-score in infants that no longer regurgitated. An explanation may be that infants that regurgitate drink larger volumes than infants who do not regurgitate. Conservative treatment (reassurance, dietary treatment, behavioral advice) resulted in a significant better outcome than natural evolution. Conclusion: Regurgitation that persisted after the age of 6 months, strongly decreased during a 3-month follow-up with conservative treatment. GERD is rare in this age group; therefore, anti-reflux medication is only seldom needed.

Hyperglycerolemia와 Congenital Adrenal Hypoplasia, Duchenne Muscular Dystrophy가 동반된 Xp21 Contiguous Gene Deletion Syndrome

신대원,허준,이홍진,박원일,이경자,신윤숙,D.R. Sjarif,B.T. Poll-The 대한소아청소년과학회 2001 Clinical and Experimental Pediatrics (CEP) Vol.44 No.1

On Xp21 region several genes such as adrenal hypoplasia congenita(AHC) gene, glycerol kinase (GK) gene and Duchenne muscular dystrophy(DMD) gene are located contiguously. If there is a long deletion in that region, various combination of genetic defect can be occurred from one kind of genetic defect to all three kinds of genetic defect simultaneously. In case of more than two genetic defects simultaneously, we call it contiguous gene deletion syndrome. The major clinical manifestations of the Xp21 contiguous gene deletion syndrome are sum of each diseases, electrolyte imbalance and hyperpigmentation for adrenal hypoplasia congenita, psychomotor retardation, letharginess and convulsion for glycerol kinase deficiency and muscle weakness and hypotonia for Duchenne muscular dystrophy. Goals of the treatment are control of each disorders, glucocorticoid and mineralocorticoid for adrenal hypoplasia congenita, low fat diet and prevention of fasting and hypercatabolic status for glycerol kinase deficiency and physiotherapy for Duchenne muscular dystrophy. In case of hyponatremia and hyperkalemia combined with hyperpigmentation, adrenal hypoplasia congenita could be suspected. In glycerol kinase deficiency, markedly elevated glycerol excretion can be detected on urine organic acid analysis by gaschromatography with mass spectrometry. On Duchenne muscular dystrophy, creatinine kinase is markedly elevated on chemistry. We report here first Korean case of Xp21 contiguous gene deletion syndrome of adrenal hypoplasia congenita, glycerol kinase deficiency and Duchenne muscular dystrophy. 저자들은 urine organic acid analysis 등의 방법을 통해, GKD와 CAH, DMD가 동시에 동반된 Xp21 contiguous gene deletion syndrome을 국내 최초로 확인, 경험하였기에 이를 보고하는 바이다. 또한, 소변 유기산검사 등의 진단방법으로써 앞으로 더욱 많은 사례를 경험할 수 있을 것으로 보며, 산전 진단의 한 방법으로 유용하게 사용될 수 있으리라 기대한다. 그리고, 다른 여러 가지의 임상증상과 특정 부위의 gene defects와의 상호연관성에 대해, 광범위한 조사와 연구가 앞으로 더 이루어져야 할 것으로 본다.

Comparing Compliance and Efficacy of Isocaloric Oral Nutritional Supplementation Using 1.5 kcal/mL or 1 kcal/mL Sip Feeds in Mildly to Moderately Malnourished Indonesian Children: A Randomized Controlled Trial

Devaera, Yoga,Syaharutsa, Danny Maesadatu,Jatmiko, Herwasto Kuncoroyakti,Sjarif, Damayanti Rusli The Korean Society of Pediatric Gastroenterology 2018 Pediatric gastroenterology, hepatology & nutrition Vol.21 No.4

Purpose: This study set out to evaluate the compliance to, and efficacy of oral supplementation, using a 1.5 kcal/mL or 1 kcal/mL sip feed, in children with mild to moderate malnutrition. Methods: This was a parallel, randomized, controlled open-label trial in children aged 3 to 6 years with a weight for height Z (WHZ) score <-1 and ${\geq}-3$, who were randomized to receive a total of 600 kcal/day from either a 1.5 kcal/mL or a 1.0 kcal/mL pediatric sip feed for 28 days. Assessments included daily study product intake, body weight, tolerance and dietary intake from solid food. Results: Of 110 children recruited, 98 ($mean{\pm}standard$ deviation of age $49{\pm}7months$) completed the study. Both sip feeds were well tolerated, with high compliance ($80{\pm}24%$ and $81{\pm}22%$ of prescribed volume in 1.5 kcal/mL and 1.0 kcal/mL groups respectively, p=0.79). Both study groups gained similar weight during the 28 days intervention period ($0.42{\pm}0.40kg$ in 1.5 kcal/mL group vs. $0.49{\pm}0.49kg$ in 1.0 kcal/mL group, p=0.43). There were no significant differences between the groups in weight gain and in the change in WHZ score over the intervention period. Dietary analysis at the end of the study did not show replacement of solid food by the oral nutritional supplements. Conclusion: In children with mild to moderate malnutrition, both 1.5 kcal/mL and 1 kcal/mL pediatric sip feeds had high compliance and were well tolerated, and were equally effective in promoting weight gain in the 28 days study period.

Determinants of Circulating Soluble Leptin Receptor and Free Leptin Index in Indonesian Pre-Pubertal Obese Male Children: A Preliminary Cross-Sectional Study

Aryono Hendarto,Dimple G. Nagrani,Anna Meiliana,Sudigdo Sastroasmoro,Damayanti R. Sjarif 대한소아소화기영양학회 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.2

Purpose: This study aimed to investigate the clinical and metabolic determinants of circulating soluble leptin receptor (CSLR) and free leptin index (FLI) in pre-pubertal obese male children. Methods: We conducted a preliminary cross-sectional study at three tertiary hospitals and one public primary school. Eighty obese male children without growth and developmental abnormalities aged 5–9 years were recruited. In these children, obesity was solely caused by excessive food intake, and not by acute illness, medications, endocrine abnormalities, or any syndrome. Body mass index (BMI), body fat mass, carbohydrate intake, fat intake, high density lipoprotein cholesterol level, low density lipoprotein cholesterol level, triglyceride level, and Homeostatic Model Assessment for Insulin Resistance are the potential determinants for leptin regulation, which is represented by CSLR level and FLI. Results: Carbohydrate was the main source of energy. BMI and body fat mass had negative weak correlation with CSLR and positive weak correlation with FLI. Furthermore, carbohydrate intake was found to be independently associated with CSLR based on the results of the multiple linear regression analysis. Following an increase in carbohydrate intake, CSLR level decreased progressively without any negative peak. Conclusion: Leptin regulation in prepubertal obese male children is associated with body composition and dietary intake. Carbohydrate intake is useful for predicting CSLR. Lipid profiles and insulin resistance are not related to both CSLR and FLI. Treatment and prevention of leptin resistance in obese children should focus on reducing BMI, fat mass, and carbohydrate intake.

Regurgitation and Gastroesophageal Reflux Disease in Six to Nine Months Old Indonesian Infants

Badriul Hegar,Debora Hindra I. Satari,Damayanti R. Sjarif,Yvan Vandenplas 대한소아소화기영양학회 2013 Pediatric gastroenterology, hepatology & nutrition Vol.16 No.4

Purpose: Regurgitation is known to peak at the age of 3-4 months, with a sharp decrease around the age of 6 months. Little is known about the natural evolution of infants who still regurgitate after the age of 6 months. Methods: Hundred thirty-one infants older than 6 months regurgitating more than once a day were followed for a period of 3 months. Results: According to our data, gastroesophageal reflux disease (GERD) is seldom at this age. Most of the infants regurgitated 3 or more times/day and spit up an estimated volume of more than 15 mL. Eighty-five parents were educated regarding frequency of feeding. There were only 6 infants that still had frequent regurgitation (>3 times/day) despite an appropriate feeding schedule. The Infant GER Questionnaire score reached a score of 0 in 50% of the infants after one month of follow-up and in 81.9% at the third month of follow-up. There was an increase of the “weightfor age z-score” trends in infants that still regurgitated at the end of follow-up and a declining z-score in infants that no longer regurgitated. An explanation may be that infants that regurgitate drink larger volumes than infants who do not regurgitate. Conservative treatment (reassurance, dietary treatment, behavioral advice) resulted in a sig-nificant better outcome than natural evolution. Conclusion: Regurgitation that persisted after the age of 6 months, strongly decreased during a 3-month follow-up with conservative treatment. GERD is rare in this age group; therefore, anti-reflux medication is only seldom needed.

Comparing Compliance and Efficacy of Isocaloric Oral Nutritional Supplementation Using 1.5 kcal/mL or 1 kcal/mL Sip Feeds in Mildly to Moderately Malnourished Indonesian Children: A Randomized Controlled Trial

Yoga Devaera,Danny Maesadatu Syaharutsa,Herwasto Kuncoroyakti Jatmiko,Damayanti Rusli Sjarif 대한소아소화기영양학회 2018 Pediatric gastroenterology, hepatology & nutrition Vol.21 No.4

Purpose: This study set out to evaluate the compliance to, and efficacy of oral supplementation, using a 1.5 kcal/mL or 1 kcal/mL sip feed, in children with mild to moderate malnutrition. Methods: This was a parallel, randomized, controlled open-label trial in children aged 3 to 6 years with a weight for height Z (WHZ) score <−1 and ≥−3, who were randomized to receive a total of 600 kcal/day from either a 1.5 kcal/mL or a 1.0 kcal/mL pediatric sip feed for 28 days. Assessments included daily study product intake, body weight, tolerance and dietary intake from solid food.Results: Of 110 children recruited, 98 (mean±standard deviation of age 49±7 months) completed the study. Both sip feeds were well tolerated, with high compliance (80±24% and 81±22% of prescribed volume in 1.5 kcal/mL and 1.0 kcal/mL groups respectively, p=0.79). Both study groups gained similar weight during the 28 days intervention period (0.42±0.40 kg in 1.5 kcal/mL group vs. 0.49±0.49 kg in 1.0 kcal/mL group, p=0.43). There were no significant differences between the groups in weight gain and in the change in WHZ score over the intervention period. Dietary analysis at the end of the study did not show replacement of solid food by the oral nutritional supplements.Conclusion: In children with mild to moderate malnutrition, both 1.5 kcal/mL and 1 kcal/mL pediatric sip feeds had high compliance and were well tolerated, and were equally effective in promoting weight gain in the 28 days study period.

Determinants of Circulating Soluble Leptin Receptor and Free Leptin Index in Indonesian Pre-Pubertal Obese Male Children: A Preliminary CrossSectional Study

Hendarto, Aryono,Nagrani, Dimple G.,Meiliana, Anna,Sastroasmoro, Sudigdo,Sjarif, Damayanti R. The Korean Society of Pediatric Gastroenterology 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.2

Purpose: This study aimed to investigate the clinical and metabolic determinants of circulating soluble leptin receptor (CSLR) and free leptin index (FLI) in pre-pubertal obese male children. Methods: We conducted a preliminary cross-sectional study at three tertiary hospitals and one public primary school. Eighty obese male children without growth and developmental abnormalities aged 5-9 years were recruited. In these children, obesity was solely caused by excessive food intake, and not by acute illness, medications, endocrine abnormalities, or any syndrome. Body mass index (BMI), body fat mass, carbohydrate intake, fat intake, high density lipoprotein cholesterol level, low density lipoprotein cholesterol level, triglyceride level, and Homeostatic Model Assessment for Insulin Resistance are the potential determinants for leptin regulation, which is represented by CSLR level and FLI. Results: Carbohydrate was the main source of energy. BMI and body fat mass had negative weak correlation with CSLR and positive weak correlation with FLI. Furthermore, carbohydrate intake was found to be independently associated with CSLR based on the results of the multiple linear regression analysis. Following an increase in carbohydrate intake, CSLR level decreased progressively without any negative peak. Conclusion: Leptin regulation in prepubertal obese male children is associated with body composition and dietary intake. Carbohydrate intake is useful for predicting CSLR. Lipid profiles and insulin resistance are not related to both CSLR and FLI. Treatment and prevention of leptin resistance in obese children should focus on reducing BMI, fat mass, and carbohydrate intake.

The impact of nucleic acid testing as a blood donor screening method in transfusion-associated hepatitis C among children with bleeding disorders in Indonesia: a single-center experience

Novie Amelia Chozie,Melati Arum Satiti,Damayanti Rusli Sjarif,Hanifah Oswari,Ni Ken Ritchie 대한혈액학회 2022 Blood Research Vol.57 No.2

Background Children with bleeding disorders, such as hemophilia and von Willebrand disease (VWD), have an increased risk of acquiring transfusion-transmitted infections (TTI). Screening methods to exclude blood donations that are at risk of transmitting infection from donors to recipients are critical to preventing disease transmission. Nucleic acid testing (NAT) is the latest blood donor-screening method. This study aimed to determine the incidence of hepatitis C virus (HCV) infection in children with hemophilia and VWD at Dr. Cipto Mangunkusumo Hospital with a history of blood transfusion before and after implementation of a NAT screening method. Methods A cohort retrospective study was conducted on children aged 0‒18 years with bleeding disorders and a history of blood transfusion. In our center, all blood transfusions before 2015 were screened using non-NAT methods, while all blood transfusions were screened using NAT starting in 2015. Eligible patient characteristics were collected from medical records. From July to December 2019, blood samples were obtained from eligible patients for anti-HCV examination. HCV RNA examinations were performed on subjects with reactive anti-HCV results, and the relative risk was calculated. Results In total, 108 eligible participants were included in this study. We observed that 91 (94.3%) patients had history of receiving non-NAT blood transfusions, while 17 (15.7%) patients received NAT-screened blood transfusions. The proportion of anti-HCV reactivity in the non-NAT group and that in the NAT group were 3.3% (3/91) and 0% (0/17), respectively. Conclusion None of the patients exhibited reactivity to anti-HCV after implementing the NAT screening method.