Damayanti Rusli Sjarif

Current information and Asian perspectives on long-chain polyunsaturated fatty acids in pregnancy, lactation, and infancy: systematic review and practice recommendations from an early nutrition academy workshop

The Early Nutrition Academy supported a systematic review of human studies on the roles of pre- and postnatal long-chain polyunsaturated fatty acids (LC-PUFA) published from 2008 to 2013 and an expert workshop that reviewed the information and developed recommendations, considering particularly Asian populations. An increased supply of n-3 LC-PUFA during pregnancy reduces the risk of preterm birth before 34 weeks of gestation. Pregnant women should achieve an additional supply ≥200 mg docosahexaenic acid (DHA)/day, usually achieving a total intake ≥300 mg DHA/day. Higher intakes (600-800 mg DHA/day) may provide greater protection against early preterm birth. Some studies indicate beneficial effects of pre- and postnatal DHA supply on child neurodevelopment and allergy risk. Breast-feeding is the best choice for infants. Breast-feeding women should get ≥200 mg DHA/day to achieve a human milk DHA content of ∼0.3% fatty acids. Infant formula for term infants should contain DHA and arachidonic acid (AA) to provide 100 mg DHA/day and 140 mg AA/day. A supply of 100 mg DHA/day should continue during the second half of infancy. We do not provide quantitative advice on AA levels in follow-on formula fed after the introduction of complimentary feeding due to a lack of sufficient data and considerable variation in the AA amounts provided by complimentary foods. Reasonable intakes for very-low-birth weight infants are 18-60 mg/kg/day DHA and 18-45 mg/kg/day AA, while higher intakes (55-60 mg/kg/day DHA, ∼1% fatty acids; 35-45 mg/kg/day AA, ∼0.6-0.75%) appear preferable. Research on the requirements and effects of LC-PUFA during pregnancy, lactation, and early childhood should continue.

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.

The role of apolipoprotein E polymorphism in improving dyslipidemia in obese adolescents following physical exercise and National Cholesterol Education Program Step II intervention.

Abstract Background: Lifestyle changes are important factors for managing dyslipidemia before considering blood lipid-lowering drugs. However, genetic factors can influence the response outcome. Objective: We aimed to determine a dyslipidemia management strategy in obese adolescents. Patients and methods: A total of 60 dyslipidemic obese adolescents received physical exercise and the NCEP step II diet for 28 days. Apolipoprotein E (apo E) genotypes and blood lipid levels were compared before and after interventions. Results: The apo E3/E3 genotype was found to be common in all subjects. Mean levels of total cholesterol, triglyceride, and low-density lipoprotein-cholesterol (LDL-C) improved in subjects with the E3 allele after the intervention, but not the E2 allele. Total cholesterol and LDL-C, but not triglyceride levels, improved in subjects with the E4 allele. Discussion: Apo E alleles might influence improvement in lipid profiles after diet and exercise interventions. These results could inform personalized dyslipidemia management in obese adolescents, to determine which subjects would benefit from blood lipid-lowering drugs.

Genetics and genomic medicine in Indonesia

Genetics and genomic medicine in Indonesia.

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

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.

Mutational analysis of exon 4 of the 6-pyruvoyl-tetrahydropterin synthase gene in an Indonesian population

The enzyme 6-pyruvoyl-tetrahydropterin synthase (PTPS), which is coded by the PTS gene, plays a key role in the biosynthesis of tetrahydrobiopterin (BH4). BH4 deficiency causes hyperphenylalaninemia (HPA). The PTS gene comprises six exons and five introns. There are several types of mutations to the PTS gene in patients with PTPS enzyme deficiency that cause functional changes in the resulting protein. Primers for mutational analysis of exon 4 of the PTS gene were designed using BioEdit and Chromas softwares. Mutations to exon 4 (56 bp in length) were identified in patients with PTPS enzyme deficiency and normal healthy patients as controls. The primers used to identify mutations to the PTS gene were optimal at 57 °C. Six new mutations and 27 variations were identified in exon 4, which included five variations that were previously described.

Variations on exon 3 of 6-pyruvoyl-tetrahydropterin synthase gene in Indonesian population

Pyruvoyltetrahydropterin synthase (PTPS) is one of the several enzymes involved in tetrahydrobiopterin (BH4) biosynthesis. The deficiency of BH4 can cause hyperphnylalaninaemia (HPA). Mutations in PTS gene can alter protein function. We conducted genetic analysis of exon 3 of PTS gene of an Indonesian patient with PTPS-deficiency and healthy individuals. Direct sequencing of DNA samples was performed from an Indonesian patient with PTPS deficiency and 33 healthy individuals. No mutation was identified in the patient sample. However, a total of 6 novel variations were recorded in exon 3 of PTS. All these variations were found to be single-base alterations. The 6 novel variations identified in exon 3 of healthy individuals in this study were missense mutations. This variation data is expected to contribute to the development of the new database of Single Nucleotide Polymorphism (SNP) on PTS as well as to serve as a biomarker for the diagnosis of patients with PTPS deficiency.

Novel variations in Exon 4 of the iduronate 2-sulfatase gene in six Indonesian patients with mucopolysaccharidosis type II

Mucopolysaccharidosis type II (MPS II) is an X-linked lysosomal storage disorder caused by the inability to produce iduronate 2-sulfatase (IDS). We genotyped exon 4 of the IDS gene in Indonesian patients with MPS II. To detect IDS gene mutations, DNA samples from 6 patients with MPS II and 49 normal individuals were analyzed with direct sequencing of exon 4. One novel mutation (c.489G>A) was identified in four of six patients. Protein analysis of these mutations revealed no amino acid sequence changes (silent mutation). Another 20 variations were found in normal individuals, including missense, nonsense, and silent mutations. The discovery of this novel mutation provides new mutational data for MPS II, whereas the identified variations strengthen the single nucleotide polymorphism database for the IDS gene. These mutation and variation data should be useful for identifying biomarkers for diagnosing MPS II.

A Novel mutation in iduronate-2-sulfatase gene Exon 6 of an Indonesian patient with Mucopolysaccharidosis type II

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare X-linked recessive disease caused mutation of the gene encoding the lysosomal enzyme iduronate-2-sulfatase (IDS). Deficient lysosomal degradation of the glycosaminoglycans dermatan sulfate and heparan sulfate by mutant IDS leads to their accumulation in multiple tissues, causing progressive tissue hypertrophy (e.g., hepatosplenomegaly and macroglossia), various deformities, and narrowing of the respiratory tract among other symptoms. Here, we searched from additional IDS mutations in Indonesian patients to provide information for establishing associations with disease traits. Exon-specific PCR amplification and sequencing of IDS gene exon 6 were conducted on DNA samples from MPS II patients and healthy controls at Cipto Mangunkusumo National Referral Hospital, Jakarta, Indonesia. A novel mutation in an Indonesian patient with MPS II was identified, a 14 bp insertion mutation (c.792_793insCCCCTGTGGCCTAC) in IDS gene exon 6 resulting in the amino acid changes p.Tyr264_X269insProLeuTrpPro and X269Thr. This novel mutation likely alters the structure and function of IDS. We are currently analyzing other IDS gene exons to identify additional mutations linked to IDS. Such studies will help clarify MPS II pathophysiology and may lead to novel treatment strategies.

Liquid chromatography-tandem mass spectrometric analyses of the amino acid profiles of normal and malnourished children treated at Cipto Mangunkusumo Hospital

Children require dietary protein for growth. The nutritional quality of proteins is influenced by their amino acid composition. Amino acids are required for life, contributing to homeostasis, immunity, growth, and development. In this preliminary study, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the amino acid profiles of glycine, alanine, proline, valine, leucine, ornithine, methionine, phenylalanine, arginine, citrulline, tyrosine, aspartic acid, and glutamic acid of normal and malnourished children treated at Cipto Mangunkusumo Hospital. A total of 60 subjects were analyzed from December 2016 to April 2017. Dry blood spots were analyzed using LC-MS/MS. The study subjects comprised 12 malnourished and 18 normal children. The mean weight, height, and z-score (weight-for-age, height-for-age, and weight-for-height) were significantly lower in the malnourished group. The coefficients of variation percentage among runs ranged from 1.76% to 12.03%. There was no significant difference between the amino acid profiles of the normal and malnourished groups, although the concentrations of glycine and glutamate were significantly higher in the malnourished group.