Pornswan Wasant
Mahidol University, Pediatrics, Emeritus
For the dystrophin gene, it has been shown that about 65% of DMD/BMD patients have detectable deletions. The majority of deletions are clustered in exons 45-53 and at the 5' terminus. We studied 14 X-linked muscular dystrophy (DMD) Thai... more
For the dystrophin gene, it has been shown that about 65% of DMD/BMD patients have detectable deletions. The majority of deletions are clustered in exons 45-53 and at the 5' terminus. We studied 14 X-linked muscular dystrophy (DMD) Thai child patients for detection of gene deletions by amplification of nine exons plus the promoter of the dystrophin gene in two multiplex polymerase chain reactions that included hot spot region (exons 45-53 and 5' terminus). There were 8 DMD patients who had incomplete gene deletion and most of the deletions were around exon 49. PCR-base assays will allow deletion detection from dry blood spot samples and prenatal diagnosis.
Research Interests: Genetics, Molecular Biology, Biology, Medicine, Biopsy, and 15 moreHumans, Child, Pubmed, Muscular Dystrophies, Polymerase Chain Reaction, Electromyography, Gene, Duchenne Muscular Dystrophy, Base Sequence, Dystrophin, Exon, Age of Onset, Molecular Sequence Data, Child preschool, and multiplex polymerase chain reaction
Three infants with documented mitochondrial fatty acid oxidation disorders are described in this report. Case 1. Carnitine/acylcarnitine translocase deficiency. (CACT) (OMIM 212138) A two-day-old male developed sudden cardiac arrest 48... more
Three infants with documented mitochondrial fatty acid oxidation disorders are described in this report. Case 1. Carnitine/acylcarnitine translocase deficiency. (CACT) (OMIM 212138) A two-day-old male developed sudden cardiac arrest 48 hours postpartum, with a previous history of early death (day 2) in siblings with a history of parental consanguinity; somnolence, inactivity, refusal to suck within 24 h, hepatomegaly, persistent hypoglycemia, hypocalcemia, hyperkalemia and severe metabolic acidosis prior to cardiac arrest. Dried blood spots by tandem mass spectrometry demonstrated 10 x elevation of palmitoylcarnitine, moderate elevation of oleylcarnitine, steroylcarnitine and myristoylcarnitine. Case 2. Medium chain acyl CoA dehydrogenase (MCAD) deficiency. (OMIM 212139) A six-week-old male infant, developed sudden cardiac arrest after contacting a viral illness, resuscitated successfully in the first episode, only to succumb during the second episode, 2 weeks apart. Plasma acylcarnitine via tandem mass spectrometry was reported normal; however, urine organic acids via gas liquid chromatography and mass spectrometry demonstrated characteristic metabolites consistent with MCADD. Case 3. Carnitine deficiency, systemic primary. (CDSP) (OMIM 212140) A one-year-old girl with progressive dyspnea since birth and a history of parental consanguinity. Severe dilated cardiomyopathy with episodes of cardiac decompensations, hepatomegaly, anemia, generalized hypotonia, but no hypoglycemia were demonstrated prior to cardiac arrest. Extremely low carnitine level noted in dried blood spots via tandem mass spectrometry.
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Lysosomal storage disorders are a heterogeneous group of biochemical genetic disorders; currently 40-50 are known. The clinical phenotype is determined by the tissue distribution of the storage material and degree of enzyme deficiency.... more
Lysosomal storage disorders are a heterogeneous group of biochemical genetic disorders; currently 40-50 are known. The clinical phenotype is determined by the tissue distribution of the storage material and degree of enzyme deficiency. The genetic transmission is mostly autosomal recessive. Lysosomal storage disorders can be divided into three groups according to the major organ system pathology: (1) Primary involvement of the central nervous system without significant somatic or skeletal pathology. Disorders of grey matter, eg gangliosidosis and disorders of white matter eg the leucodystrophy are the most common; (2) Primary involvement of the reticuloendothelial system with or without associated neuropathology, eg Niemann-Pick disease and Gaucher disease; (3) Multisystem involvement in which skeletal manifestations are prominent features. The mucopolysaccharidosis and mucolipidoses are the two major forms with this clinical phenotype. Lysosomal storage disorders identified at Siriraj Hospital are neuronal ceroid lipofuscinosis, GMI gangliosidosis, mucolipidosis II, Maroteaux-Lamy, sialidosis, Sly syndrome, Hunter syndrome, Morquio syndrome, Gaucher disease, Niemann-Pick, Sandhoff disease, Pompe's disease and many more. Most patients came from the provinces where consanguinity is common. Confirmation usually is done by enzyme assays using skin fibroblast culture or leucocytes. Genetic counseling is extremely important and prenatal diagnosis is recommended to high-risk couple.
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Fetuses exposed to Warfarin in the first trimester of pregnancy have an increased risk of embryopathy which consists of nasal hypoplasia and stippled epiphyses, known as fetal warfarin syndrome or warfarin embryopathy. We herein report a... more
Fetuses exposed to Warfarin in the first trimester of pregnancy have an increased risk of embryopathy which consists of nasal hypoplasia and stippled epiphyses, known as fetal warfarin syndrome or warfarin embryopathy. We herein report a first case of an infant with fetal warfarin syndrome in Thailand. The patient was an offspring of a 34-year-old mother with history of SLE and arterial embolism for several years. She had an unplanned pregnancy while taking warfarin. The patient developed difficulty breathing in the first few hours after birth from severe nasal hypoplasia. He also had short limbs, brachydactyly, nail hypoplasia, and calcifications in the epiphyseal regions of humeri, femora and vertebrae radiographically. The patient eventually died from respiratory failure at 6 months of age.
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Research Interests: Pediatrics, Medicine, Multidisciplinary, Probability, Multivariate Analysis, and 15 moreDecision Trees, Humans, Markov chains, Inborn errors of metabolism, New Economic Models, Newborn Screening, PLoS one, Newborn Infant, Quality adjusted life years, Cost Benefit Analysis, MAPLE SYRUP URINE DISEASE, Propionic acidemia, Methylmalonic acidemia, Neonatal screening, and biotinidase deficiency
Gaucher's disease, a lysosomal disorder, is not a common disease in Thailand. During the period 1966-1998 we saw 20 patients with Gaucher's disease at the Department of Pediatrics. Siriraj Hospital. The patients came from different... more
Gaucher's disease, a lysosomal disorder, is not a common disease in Thailand. During the period 1966-1998 we saw 20 patients with Gaucher's disease at the Department of Pediatrics. Siriraj Hospital. The patients came from different regions of the country but mostly from the central part of Thailand. There were 8 males and 12 females from 13 families of Thai, Thai-Chinese, Thai-Laos and Chinese-Chinese in origin. A history of consanguinity was present in 2 families. The age of onset was 2 months-4 years and the age when they were diagnosed was 4 months-15 years. The most common clinical features included splenomegaly, hepatomegaly, growth retardation, pallor, bleeding disorders and neurological abnormalities. The diagnosis was made by the clinical manifestations, hematologic complications and demonstration of Gaucher cells in the bone marrow and/or other tissues. In one family, the diagnosis was confirmed by evaluation of glucocerebrosidase activities in skin fibroblasts. The management of these patients was symptomatic ie packed red cell and platelet transfusion, splenectomy and other supportive measures. Most patients died of bleeding or infection at an early age.
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A newborn screening program for congenital hypothyroidism (CH) and phenylketonuria (PKU), a pilot study, was initiated at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital Faculty of Medicine, Mahidol University in... more
A newborn screening program for congenital hypothyroidism (CH) and phenylketonuria (PKU), a pilot study, was initiated at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital Faculty of Medicine, Mahidol University in Bangkok, Thailand from January 1994 to December 1998, using dried blood spots (DBS). A total of 18,739 infants (out of 85,150 livebirths) were screened (22 % coverage). Three cases of congenital hypothyroidism (CH) were identified (incidence of 1: 6,246, livebirths), by enzyme linked immunosorbent (ELISA) and fluoroimmunoassays using a cut-off level of TSH >20 microlU/ml: the recall rate of 0.24%. The screening for PKU was done by fluorometric (Guthrie) and enzyme linked immunosorbent (ELISA) methods; using cut-off levels of phenylalanine > 4 mg/dl and > 3.6 mg/dl respectively, with a recall rate of 0.13%. There was no PKU found. Our study, a voluntary program, emphasizes the importance of parental education and consent; specimen collection and handling; appropriate follow-up and referral to specialists for treatment and counseling. Routine newborn screening for CH and PKU is being established to ascertain the maximum coverage, using recommendations and guidelines from this pilot study.
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Genetic skeletal dysplasias are a heterogeneous group of genetic disorders associated with abnormalities in the skeletal system frequently presenting with disproportionate short stature. There are over 100 distinct skeletal dysplasias... more
Genetic skeletal dysplasias are a heterogeneous group of genetic disorders associated with abnormalities in the skeletal system frequently presenting with disproportionate short stature. There are over 100 distinct skeletal dysplasias which have been classified primarily on the basis of the clinical or radiographic characteristics. We have identified many genetic skeletal dysplasia disorders at Department of Pediatrics, Siriraj Hospital, Bangkok, Thailand. We have cases of achondroplasia, hypochondroplasia, pseudoachondroplasia, atelosteogenesis, pyknodysostosis, spondyloepiphyseal dysplasia (SED) congenita, spondylometaepiphyseal dysplasia (SMED), osteogenesis imperfecta type I, II and III, Ellis-van Creveld syndrome, cleidocranial dysostosis, thanatophoric dysplasia, rhizomelic chondrodysplasia punctata, trichorhinophalangeal syndrome, mucopolysaccharidosis I, II, IV and VI, mucolipidosis II, osteopetrosis, camptomelic dysplasia, metaphyseal dysplasia with spine involvement (Kozlowski type), Langer-Gideon syndrome and hypophosphatemic rickets. We have established a Genetic Skeletal Dysplasia Clinic at Siriraj Hospital since 1992, and see referrals from around the country. Genetic counseling is provided, including prenatal diagnosis and a multidisciplinary approach.
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BackgroundPrimary carnitine deficiency (PCD) is screened by expanded newborn screening (NBS) using tandem mass spectrometry (MS/MS) that can detect both affected neonates and mothers. This study aimed to delineate the clinical,... more
BackgroundPrimary carnitine deficiency (PCD) is screened by expanded newborn screening (NBS) using tandem mass spectrometry (MS/MS) that can detect both affected neonates and mothers. This study aimed to delineate the clinical, biochemical, and molecular findings of Thai PCD patients.MethodsExpanded NBS using MS/MS was implemented in Bangkok and 146,757 neonates were screened between 2014 and 2018. PCD was screened by low free carnitine (C0) levels in dried blood spots. Plasma C0 levels and C0 clearance values were measured in neonates and their mothers with positive screening results. Clinically diagnosed cases were described. The coding regions and intron‐exon boundaries of the SLC22A5 gene were sequenced in all cases with low plasma C0 levels.ResultsThere were 14 cases with confirmed PCD: two clinically diagnosed cases, and 12 cases identified through NBS including five newborns, six mothers, and one older sibling. Thus, the incidence of PCD in neonates was 1:29,351. All affected...
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SummaryTetrahydrobiopterin (BH4) deficiency comprises heterogeneous disorders resulting in hyperphenylalaninaemia (HPA) and lack of monoamine neurotransmitters. Among these, 6‐pyruvoyl‐tetrahydropterin synthase (PTPS) deficiency is the... more
SummaryTetrahydrobiopterin (BH4) deficiency comprises heterogeneous disorders resulting in hyperphenylalaninaemia (HPA) and lack of monoamine neurotransmitters. Among these, 6‐pyruvoyl‐tetrahydropterin synthase (PTPS) deficiency is the most common disorder. We report a female Thai patient with PTPS deficiency who was initially detected by newborn screening for HPA, and later treated by supplements of BH4, l‐dopa/carbidopa, and 5‐hydroxytryptophan. Monitoring of serum prolactin representing dopamine sufficiency is used for optimizing the dosage of l‐dopa. She showed a remarkable progress of development despite delayed treatment at 5 months of age. Mutation analysis revealed two heterozygous missense mutations of the PTS gene: c.259C>T (p.P87S) inherited from the father; and c.147T>G (p.H49Q) inherited from the mother. The latter is a novel mutation that affects the pterin‐binding site of the PTPS enzyme. This novel mutation expands the mutation spectrum of PTPS deficiency. Nota...
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Research Interests: Genetics, M Rna Processing, Biology, Cell Cycle, Medicine, and 15 moreBiological Sciences, Humans, Hair, Female, Infant, Gene, Dwarfism, Hirschsprung disease, Base Sequence, Autosomal Recessive, Molecular Sequence Data, DNA mutational analysis, Immunologic deficiency syndromes, Fatal outcome, and Failure to Thrive
Maple syrup urine disease is a rare inborn error of metabolism, characterized by elevated plasma levels of branched chain amino acids and urinary excretion of branched chain keto acids. Plasma amino acid levels in two subjects were... more
Maple syrup urine disease is a rare inborn error of metabolism, characterized by elevated plasma levels of branched chain amino acids and urinary excretion of branched chain keto acids. Plasma amino acid levels in two subjects were followed by deproteinizing plasma, derivatizing the free amino acids with phenylisothiocyanate, and analysis by HPLC. The results indicate that valine, leucine and isoleucine are elevated in Maple syrup urine disease, and that leucine remains high even after dietary treatment.
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From a retrospective study in Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital Faculty of Medicine, Mahidol University in Bangkok (1983-1988), the estimated pediatric patients with clinically suspected IEM are... more
From a retrospective study in Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital Faculty of Medicine, Mahidol University in Bangkok (1983-1988), the estimated pediatric patients with clinically suspected IEM are approximately 2-4% of total annual pediatrics admission of 5,000 or more. This is, a low estimation since survey from all teaching hospitals in the country including the largest Children's Hospital in Bangkok indicated the presence of numerous IEM. However, most IEM were clinically diagnosed with limited laboratory facilities. We started a collaboration with Magee Womens Hospital of Pittsburgh and NeoGen Screening, USA; using tandem mass spectrometry to diagnose high risk infants and children for IEM from July 1993 to March 1998. Of total 146 samples sent, we detected numerous metabolic disorders (11.2%) eg phenylketonuria, organic acidemia, maple syrup urine disease, isovaleric acidemia, methylmalonic acidemia, albinism, translocase/carnitine palmitoyltra...
Research Interests: Pediatrics, Thailand, Medicine, Humans, Child, and 13 moreFatty acids, Pubmed, Inborn errors of metabolism, Male, Infant, Newborn Screening, Newborn Infant, Amino Acids, Liquid Chromatography / Electrospray Ionization Mass Spectrometry, Public health systems and services research, Retrospective Studies, MAPLE SYRUP URINE DISEASE, and Methylmalonic acidemia
Three cases of a small supernumerary chromosomal anomaly of essentially unknown origin associated with wide variability of clinical expression are reported. Case II has, in addition, a pericentric inversion of chromosome 5, which enables... more
Three cases of a small supernumerary chromosomal anomaly of essentially unknown origin associated with wide variability of clinical expression are reported. Case II has, in addition, a pericentric inversion of chromosome 5, which enables us to propose a mechanism, involving an unsuccessful crossing over, for the origin of the supernumerary chromosome.
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Generalized lipodystrophy is a rare condition which can be divided into congenital and acquired types, based on the age at presentation and pattern of inheritance. The congenital type of generalized lipodystrophy or Lawrence-Seip syndrome... more
Generalized lipodystrophy is a rare condition which can be divided into congenital and acquired types, based on the age at presentation and pattern of inheritance. The congenital type of generalized lipodystrophy or Lawrence-Seip syndrome presents in first two years of life and is inherited in an autosomal recessive pattern. The diagnosis is made on the basis of loss of body fat, muscular hypertrophy, acanthosis nigricans, hirsutism, hepatomegaly with fatty liver, hyperlipidemia and hyperglycemia with insulin resistance. A 2 1/2-year-old Thai girl with the clinical features of Lawrence-Seip syndrome is reported. Abnormal platelet function was detected in this girl.
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The incidence of IBEM in Thailand is yet unknown, however, by estimation it is generally accepted to be 1 in 5,000. From a recent survey in 7 medical schools from different parts of the country and a largest pediatric hospital in Bangkok,... more
The incidence of IBEM in Thailand is yet unknown, however, by estimation it is generally accepted to be 1 in 5,000. From a recent survey in 7 medical schools from different parts of the country and a largest pediatric hospital in Bangkok, we found numerous cases of IBEM nationwide. These are amino acids disorders, carbohydrate disorders, urea cycle defects, peroxisomal, lysosomal storage disorders and many others. Since Thais are quite homogeneous in their genetic make-up; it is, therefore, very likely that IBEM is much more prevalent than we realized. With the exception of thalassemias, IBEM is very common in Thailand and other countries in the Asia-Pacific region. It is a real burden, indeed, since the consequences of IBEM are very serious, eg permanent damage to the CNS causing mental retardation, epilepsy, blindness, deafness and shortened life-span of individuals. Newborn screening for IBEM has been initiated at Siriraj and Ramathibodi Hospital Medical Schools of Mahidol University in 1993. There is yet no national screening program, although a pilot program was launched in the North, Northeast and the South by the Ministry of Health in 1991. Main problems we are facing include: only a handful of clinicians and scientists with expertise in IBEM; no well-equipped laboratory facilities; lack of funding and well-organized plan.
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Analysis of plasma free amino acid levels is important for diagnosis of inborn errors of metabolism. Traditionally, this is performed using commercially available dedicated amino acid analyzers, but few such instruments are available in... more
Analysis of plasma free amino acid levels is important for diagnosis of inborn errors of metabolism. Traditionally, this is performed using commercially available dedicated amino acid analyzers, but few such instruments are available in Thailand, and many are not used in routine operations. Here, the authors describe the analysis of plasma free amino acid levels in 57 normal children by reverse-phase HPLC and pre-column derivatization with phenylisothiocyanate. Plasma free amino levels are reported as mean +/- SD and 95 per cent confidence interval of mean for each of 5 age groups: 0-6 months; 6-12 months; 1-3 years; 3-6 years; 6-12 years. Mean amino acid levels were generally similar in all age groups (p > or = 0.01), except that hydroxyproline tended to be higher in the 0-6 months age group compared to other age groups (p<0.01). Comparisons were made between the present data with the normal free plasma amino acid levels in children of similar age groups reported both in Thai...
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We had studied inherited metabolic disorders at the Department of Pediatrics, Siriraj Hospital Faculty of Medicine, Mahidol University since 1987 using limited resources available and collaboration with other laboratories, both in... more
We had studied inherited metabolic disorders at the Department of Pediatrics, Siriraj Hospital Faculty of Medicine, Mahidol University since 1987 using limited resources available and collaboration with other laboratories, both in Thailand and The United States. Since April 1998, we started a collaboration with MILS and Kanazawa Medical University, the Japan, studying inborn errors of metabolism in Asian Countries using urine filter paper and a new GC/MS method. We have since successfully discovered several patients with metabolic disorders. Out of 33 (high-risk) cases we sent for biochemical diagnosis (during April-July 1998), 13 abnormal results were found which is approximately 39.4%. Inherited metabolic disorders identified were as follows: medium-chain acyl CoA dehydrogenase deficiency (MCAD), multiple carboxylase deficiency (MCD), methylmalonic acidemia (MMA), Fanconi syndrome, galactosemia and neuroblastoma.
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Molecular defects in the gene encoding the enzyme iduronate-2-sulfatase (IDS) result in Hunter disease (mucopolysaccharidosis type II, MPS II). To determine the molecular basis of MPS II in Thailand, the IDS gene was analysed in 20 Thai... more
Molecular defects in the gene encoding the enzyme iduronate-2-sulfatase (IDS) result in Hunter disease (mucopolysaccharidosis type II, MPS II). To determine the molecular basis of MPS II in Thailand, the IDS gene was analysed in 20 Thai patients with Hunter syndrome from 18 unrelated families. A total of 19 different mutations, including 9 missense mutations, 3 nonsense mutations, 3 splice site alterations, 1 deletion, 2 indels, and 1 rearrangement were identified, 8 of which were novel (p.R101C, p.D148V, p.G224A, p.K227E, p.E254X, p.W337X, c.440_442delinsTT and c.720_731delinsTTTCAGATGTTCTCCCCAG). Evaluation of the IDS activity of two hemizygous variants identified in the same patient, p.R101C and p.R468Q, by expression of IDS with the individual mutations in COS 7 cells indicated that only the p.R468Q mutation affected IDS protein activity. Two exonic mutations, c.257C&gt;T (p.P86L) and c.418G&gt;A, were found to activate multiple cryptic splice sites, resulting in aberrantly spliced transcripts. Thus, MPS II in Thailand is caused by a diverse set of defects affecting both IDS protein production and activity.
Research Interests: Biology, Medicine, Cercopithecus aethiops, Humans, Child, and 15 moreGenetic Testing, Mutation, Animals, Alternative splicing, Glycoproteins, Phenotype, Enzyme, Clinical Sciences, Hunter Syndrome, Asian Continental Ancestry Group, Alternative Splicing, Case Control Studies, Severity of Illness Index, DNA mutational analysis, and Child preschool
Remarkable improvements in public health, nutrition, hygiene, and availability of medical services in the last 20 years have significantly reduced infant and childhood mortality in Thailand. Therefore, many rare and previously... more
Remarkable improvements in public health, nutrition, hygiene, and availability of medical services in the last 20 years have significantly reduced infant and childhood mortality in Thailand. Therefore, many rare and previously unidentified genetic disorders, which, in the past, usually led to the death of affected infants before a definitive diagnosis, have now been increasingly recognized. Recently, we identified three unrelated patients from Thailand who suffered from citrullinemia, one of five inherited types of urea cycle disorders. All were diagnosed within their first few weeks of life. Biochemical analyses, including plasma amino acid and urine organic acid profiles, are consistent with argininosuccinate synthetase (ASS) deficiency. Extensive mutation study by direct genomic sequencing of ASS demonstrated a homozygous G117S mutation in one patient and homozygous R363W mutations in the other two families.
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Two Thai patients diagnosed with Hurler syndrome (mucopolysaccharidosis type 1, MPS I) were found to have no detectable alpha-iduronidase (E.C. 3.2.1.76) activity in leukocytes, while normal Thai children all had significant activity,... more
Two Thai patients diagnosed with Hurler syndrome (mucopolysaccharidosis type 1, MPS I) were found to have no detectable alpha-iduronidase (E.C. 3.2.1.76) activity in leukocytes, while normal Thai children all had significant activity, with a mean of 135 +/- 30 nmol/mg/18h. One patient was heterozygous for A75T (311G>A) and S633L (1986C>T) mutation, previously reported to cause MPS I, together with 9 other heterozygous polymorphisms also found in normal controls. The other patient had the previously described frameshift mutation 252insert C and a new nonsense mutation E299X (983G>T).
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Paternal microdeletion of chromosome 15 at q11-q13 has been reported in 75% of Prader-Willi syndrome (PWS) patients in western countries. Diagnosis of PWS in Thailand is mainly based on clinical observation and, in some cases, confirmed... more
Paternal microdeletion of chromosome 15 at q11-q13 has been reported in 75% of Prader-Willi syndrome (PWS) patients in western countries. Diagnosis of PWS in Thailand is mainly based on clinical observation and, in some cases, confirmed by conventional cytogenetic analysis. Loss of a tiny segment in this region (microdeletion) has made it difficult to discriminate from the normal karyotype. An attempt to solve this problem has been made by using a high resolution chromosome culture. However, this method is a tedious and time-consuming technique which is suitable for only experienced cytogeneticists. We report molecular cytogenetic analysis for PWS in Thai patients using FISH in addition to standard GTG- banding chromosome analysis. Nine Thai patients clinically diagnosed or with a suspicion of PWS were investigated. The FISH probes consist of the region-specific probes (SNRPN or D15S10 probe) and two chromosome 15-specific control probes (D15Z1 centromeric and PML chromosome 15 long...
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Down Syndrome Parents' Support Group Siriraj Hospital was established on February 14, 1993. It consists of a group of pediatricians, nurses, parents of children with Down Syndrome (DS) who received care at the Genetics Clinic,... more
Down Syndrome Parents' Support Group Siriraj Hospital was established on February 14, 1993. It consists of a group of pediatricians, nurses, parents of children with Down Syndrome (DS) who received care at the Genetics Clinic, Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital. The objective is to educate parents with DS children whose diagnosis of DS given at birth causing grief and disappointment which led to abandonment of these children at Siriraj Hospital almost every other month (fifteen years ago) due to lack of education on the part of the medical professionals. Down Syndrome Parents' Support Group Siriraj Hospital received financial support from Terres des hommes of the Netherlands in the first 6 years. Later it received partial financial support from a government agency; however, the majority of the funding came from private donations. Throughout the years, the group had several successful activities: Siriraj Down Syndrome ...
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BackgroundGenetic services at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital was established since 1960, providing genetic counseling and cytogenetic laboratory. Since 1987, the clinical genetic services have expanded... more
BackgroundGenetic services at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital was established since 1960, providing genetic counseling and cytogenetic laboratory. Since 1987, the clinical genetic services have expanded to include other areas with a mandate of providing for comprehensive genetic services with a primary role in diagnosis, counseling and prevention.MethodsThe establishment of genetic services at Siriraj Hospital was reviewed.ResultsOur services include (I) Genetic counseling program: 4 specialty clinics Genetic Clinic received referrals from Bangkok and provincial hospitals all over the country; Birth Defects Clinic (established in 1991) providing services for patients with cleft lip/palate, neural tube defects, arthrogryposis, and limb anomalies; Genetic Skeletal Dysplasia Clinic [1992] providing services for patients with achondroplasia, osteogenesis imperfecta, and metabolic bone diseases (mucopolysaccharidosis); Down Syndrome Clinic [1993] serving more than 600 families, providing genetic counseling, medical checkup, referral to early stimulation program and assisting these children toward integration; (II) Genetic screening program: newborn screening for genetic metabolic disorders (congenital hypothyroidism and phenylketonuria) has been a routine screen since year 2005. We have provided expanded newborn screening to detect 40 disorders of inborn errors of metabolism (IEM) since 2014, and have performed the screening more than 35,000 samples per year; (III) Genetic laboratory: initially only conventional cytogenetic analysis, subsequently biochemical genetics laboratory was established. Currently numerous IEM e.g., amino acid, carbohydrate, urea cycle, organic acid, fatty acid oxidation are being identified. The Genetic Metabolic Center was established since June 2001 and has served infant and children with IEM all over the country; (IV) non-governmental organization: Down Syndrome Parents Support Group at Siriraj Hospital was founded in 1993, providing more holistic approach and personal services to individuals and their families.ConclusionsGenetic services at Siriraj may serve as a model for public heath setting.
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Background A pilot expanded newborn screening (NBS) program to detect inborn errors of metabolism (IEM) using tandem mass spectrometry (TMS) began at Siriraj Hospital, Bangkok, Thailand in May, 2014, with funding support from National... more
Background A pilot expanded newborn screening (NBS) program to detect inborn errors of metabolism (IEM) using tandem mass spectrometry (TMS) began at Siriraj Hospital, Bangkok, Thailand in May, 2014, with funding support from National Health Security Office (NSHO).
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BackgroundDown Syndrome (DS) is a genetic disorder caused by extra copy of chromosome 21 resulting in delayed development/intellectual disability, congenital heart diseases, congenital hypothyroidism etc. It is a common disorder with... more
BackgroundDown Syndrome (DS) is a genetic disorder caused by extra copy of chromosome 21 resulting in delayed development/intellectual disability, congenital heart diseases, congenital hypothyroidism etc. It is a common disorder with incidence of 1:800 live births. Shock and grief occurs when physician inform parents of their infant’s diagnosis. Infants with DS were abandoned due to lack of education among doctors, nurses and parents. Therefore, an educational program for parents, medical professionals and teachers was established at Siriraj Hospital since 1987.MethodsThe program aims as follows: (I) to educate parents of children with DS (II) to share experiences and to provide emotional support (III) to raise awareness among the government and the public, and to provide an appropriate knowledge and up-to-date information (IV) to empower parents to voice their demands and basic rights.ResultsThe support group has employed certain practical and viable means. Particular efforts can be highlighted as follow: (I) having produced educational materials; (II) having provided counseling and emotional support in time of crises, especially at the time of birth. The early stimulation programs are available and sustained throughout; (III) having run Down Syndrome Annual Meeting at Siriraj Hospital since 1991; (IV) having organized Down Syndrome Annual Provincial Lecture Tour in collaboration with regional hospitals since 1997, 16 tours have been launched; (V) having worked with Ministry of Public Health since 1991. The proposal of establishing Child Development Center for the improvement of quality of life of children with DS has been accepted and become materialized; (VI) having joined other disabilities group and finally the Educational Act of 1999 was passed.ConclusionsSome of these efforts could be regarded as proud success. However being far from having realized all the objectives, undoubtedly there are much works to be done, and sustained support very much sought.
BackgroundMultiple acyl-CoA dehydrogenase deficiency (MADD) is caused by mutations in the alpha (ETFA) and beta (ETFB) subunits of electron transfer flavoprotein, and electron transfer flavoprotein dehydrogenase (ETFDH) which involves in... more
BackgroundMultiple acyl-CoA dehydrogenase deficiency (MADD) is caused by mutations in the alpha (ETFA) and beta (ETFB) subunits of electron transfer flavoprotein, and electron transfer flavoprotein dehydrogenase (ETFDH) which involves in the mitochondrial electron transport from acyl CoAs to ubiquinone. Thus the mitochondrial oxidations of glutaryl CoA and branched-chain organic acids, and beta-oxidation of fatty acids are impaired. The phenotype is classified into neonatal-onset (severe), infantile-onset (intermediate), and late-onset (myopathic) forms.MethodsWe retrospectively reviewed the clinical features of patients with MADD who were diagnosed by urine organic acids or blood acylcarnitine analysis at Department of Pediatrics, Faculty of Medicine Siriraj Hospital. Molecular analysis was performed in biochemically confirmed cases.ResultsAmong 11 Thai patients with MADD, the most common form is the late-onset (8 cases), 2 cases with the neonatal-onset form, and 1 case with the infantile-onset form. All cases with the late-onset form presented with muscle symptoms characterized by neck weakness. Muscle biopsy showed lipid myopathy. Some of them had hypoglycemia and cardiomyopathy. Interestingly, three cases had excessive weight loss. All late-onset cases were responsive to riboflavin treatment. Two patients with neonatal onset presented with hypoglycemia, acidosis, hyperammonemia, and sweaty feet odor since 1 day of age. Hypospadias was noted in one case, and mild dysmorphic face in another. The 2 cases were fatal, and died in infancy. One case with probably intermediate form was identified by newborn screening, and only mild acidosis was noted at 7 days of age. Not all patients with the late-onset form showed the characteristic profiles in blood acylcarnitines and urine organic acids. The c.250G>A (p.A84T) mutation in the ETFDH gene is commonly found in our late-onset, riboflavin-responsive patients.ConclusionsWe report a phenotypic spectrum of MADD in Thai population. The ETFDH mutations could predict the clinical phenotype and riboflavin responsiveness.
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BackgroundCraniofacial anomalies (CFA) result from interruption of normal embryologic growth and differentiation of the face and skull, and can be classified in several groups, such as branchial arch syndromes, craniosynostosis, orofacial... more
BackgroundCraniofacial anomalies (CFA) result from interruption of normal embryologic growth and differentiation of the face and skull, and can be classified in several groups, such as branchial arch syndromes, craniosynostosis, orofacial clefts, and encephalocele. Management of CFA requires multidisciplinary team. Cranio-maxillo-facial clinic at Siriraj hospital was founded more than 15 years, and consists of experts from multiple medical and surgical specialties, such as plastic surgeon, neurosurgeon, ophthalmologist, otolaryngologist, orthodontist, and clinical geneticist.MethodsA retrospective chart review of all children clinically diagnosed with CFA who were seen at Siriraj hospital was performed. Specific syndromes in which CFA are the primary feature will be reviewed here.ResultsCommon syndromes with CFA in our hospital are orofacial clefts, especially cleft lip/palate, and oculo-auriculo-vertebral (OAV) spectrum. In recent years, we found that diabetic embryopathy and prenatal exposure to teratogen increase in patients with CFA.ConclusionsClinical approach in diagnosing syndromes associated with CFA includes good history taking (prenatal, perinatal and postnatal history), family history, careful physical examination, and investigations. Clinical diagnosis may require gestalt diagnosis and pattern recognition on several key features. However, although advances in genetic testing (e.g., fluorescent in situ hybridization, chromosome microarray, whole exome sequencing) play an important role in diagnosis of genetic syndromes associated with CFA; many genetic syndromes still require the expertise of clinical geneticist in clinical recognition which is regard as the cornerstone of establishing the diagnosis.
The study of inherited metabolic disorders (IMD) in Thailand is in its infancy when compare with developed countries. Prior to 1987, majority of these disorders were clinically diagnosed since there were only a handful of clinicians and... more
The study of inherited metabolic disorders (IMD) in Thailand is in its infancy when compare with developed countries. Prior to 1987, majority of these disorders were clinically diagnosed since there were only a handful of clinicians and scientists with expertise in inborn errors of metabolism, lack of well-equipped laboratory facilities and government support. In developing countries, inherited metabolic disorders are not considered a priority due to the prevalence of infectious diseases such as HIV infection and congenital infections. A multicentre survey conducted in 1994 and 2001 revealed the existence of numerous cases of IMD from all over the country. Case reports and publications on IMD in Thai (and international) medical journals in past 20 years had undoubtedly raised its awareness among Thai paediatricians and scientists. In 2001, the Genetic Metabolic Centre was first established in Siriraj Hospital Faculty of Medicine, Thailand. Numerous new cases of IMD had been identifi...
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Urea Cycle Disorders (UCD) is an inborn error of urea synthesis in which ammonium and other nitrogenous precursors of urea accumulate leading to episodic coma and a high mortality rate. Therapy with peritoneal dialysis, essential amino... more
Urea Cycle Disorders (UCD) is an inborn error of urea synthesis in which ammonium and other nitrogenous precursors of urea accumulate leading to episodic coma and a high mortality rate. Therapy with peritoneal dialysis, essential amino acids or their nitrogen-free analogues has increased survival. The authors report 5 cases of urea cycle disorders, all of whom developed and were rescued from hyperammonemic coma. However, the eventual outcome was quite variable. Argininosuccinate lyase deficiency (ALD) Case 1. A 2 month old male infant, a product of a consanguineous marriage (Suphanburi province); developed poor feeding on day 7, lethargy, convulsion, hepatomegaly and respiratory alkalosis leading to respiratory failure and coma. Hyperammonemia, elevation of glutamic acid and argininosuccinic acid and its anhydrides confirmed the diagnosis of ALD. He is now 9 years old and severely retarded. Case 2. A male infant with history of lethargy, poor feeding on day 3, treated as sepsis and ...
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Remarkable improvements in public health, nutrition, hygiene, and availability of medical services in the last 20 years have significantly reduced infant and childhood mortality in Thailand. Therefore, many rare and previously... more
Remarkable improvements in public health, nutrition, hygiene, and availability of medical services in the last 20 years have significantly reduced infant and childhood mortality in Thailand. Therefore, many rare and previously unidentified genetic disorders, which, in the past, usually led to the death of affected infants before a definitive diagnosis, have now been increasingly recognized. Recently, we identified three unrelated patients from Thailand who suffered from citrullinemia, one of five inherited types of urea cycle disorders. All were diagnosed within their first few weeks of life. Biochemical analyses, including plasma amino acid and urine organic acid profiles, are consistent with argininosuccinate synthetase (ASS) deficiency. Extensive mutation study by direct genomic sequencing of ASS demonstrated a homozygous G117S mutation in one patient and homozygous R363W mutations in the other two families.
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Three infants with documented mitochondrial fatty acid oxidation disorders are described in this report. Case 1. Carnitine/acylcarnitine translocase deficiency. (CACT) (OMIM 212138) A two-day-old male developed sudden cardiac arrest 48... more
Three infants with documented mitochondrial fatty acid oxidation disorders are described in this report. Case 1. Carnitine/acylcarnitine translocase deficiency. (CACT) (OMIM 212138) A two-day-old male developed sudden cardiac arrest 48 hours postpartum, with a previous history of early death (day 2) in siblings with a history of parental consanguinity; somnolence, inactivity, refusal to suck within 24 h, hepatomegaly, persistent hypoglycemia, hypocalcemia, hyperkalemia and severe metabolic acidosis prior to cardiac arrest. Dried blood spots by tandem mass spectrometry demonstrated 10 x elevation of palmitoylcarnitine, moderate elevation of oleylcarnitine, steroylcarnitine and myristoylcarnitine. Case 2. Medium chain acyl CoA dehydrogenase (MCAD) deficiency. (OMIM 212139) A six-week-old male infant, developed sudden cardiac arrest after contacting a viral illness, resuscitated successfully in the first episode, only to succumb during the second episode, 2 weeks apart. Plasma acylcarn...
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Thailand Task Force on Birth Defects and Disabilities was first organized in 2008. From 2011-2014, Birth Defects Association (Thailand) received funding from ThaiHealth Promotion Foundation and the outcomes are: (I) pilot program on Birth... more
Thailand Task Force on Birth Defects and Disabilities was first organized in 2008. From 2011-2014, Birth Defects Association (Thailand) received funding from ThaiHealth Promotion Foundation and the outcomes are: (I) pilot program on Birth Defects Registry (BDR), both on case record form (CRF) and later developed into BDR Online; in 22 out of 77 provinces; (II) eleven health districts model in 11 provinces focus on holistic approach on prevention and care of 5 chosen disorders-down syndrome (DS), neural tube defects (NTD), cleft lip/palate (CL/P), limb anomalies (LA) and duchenne muscular dystrophy (DMD); (III) manuals and care map for five chosen birth defects for provincial and community hospitals completed; (IV) memorandum of understanding (MOU) was signed in 2012 between four ministries (Health, Education, Social Welfare and Human Security) and interior two organizations (National Health Security Office and ThaiHealth Promotion Foundation) including Birth Defects Association (Tha...
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Phenylketonuria (PKU) is an autosomal recessive amino acid metabolism disorder caused by variants in the gene encoding phenylalanine hydroxylase (PAH; EC1.14.16.1). This study aimed to assess the specific heterogeneity of PAH variants... more
Phenylketonuria (PKU) is an autosomal recessive amino acid metabolism disorder caused by variants in the gene encoding phenylalanine hydroxylase (PAH; EC1.14.16.1). This study aimed to assess the specific heterogeneity of PAH variants found in Thai population as well as evaluate enzyme activity and expression of novel variants. PAH gene from 13 patients was analyzed by PCR amplification and direct Sanger-sequencing of 13 exons of the coding region. The novel variants were transiently transfected in COS-7 cells for functional verification. Eleven different PAH variants were identified: all pathogenic variants were missense variants, of which the most frequent variant was p.R169L, accounting for 24% (6/25) of all identified alleles. Two novel variants p.R169L and p.Y317N and previously reported variants with mutated residues at the same positions (p.R169H and p.Y317H) were expressed in COS-7 cells. These showed mildly impaired residual activity levels (42.3-63.1% of wild type), while ...
OBJECTIVES Neural tube defects (NTDs), (including anencephaly, meningomyelocele and encephalocele), are among the most common birth defects, with high associated mortality and morbidity. NTDs occur in 1-5 per 1,000 births, with marked... more
OBJECTIVES Neural tube defects (NTDs), (including anencephaly, meningomyelocele and encephalocele), are among the most common birth defects, with high associated mortality and morbidity. NTDs occur in 1-5 per 1,000 births, with marked geographic and ethnic variations. However, there are few data concerning the incidence, associated anomalies, treatment and outcome of NTDs in Thailand. The objective of this study is to analyze data on NTD cases from 1990-1999 at Siriraj Hospital, a hospital with 18,000-20,000 deliveries annually. MATERIAL AND METHOD A retrospective chart review of patients with NTDs who were born at or referred to Siriraj Hospital 1990-1999 was performed. RESULTS During the 10 year period we examined, there were 115 patients with NTDs treated in the Department of Pediatrics as well as in other Departments at Siriraj Hospital. The incidence of NTD is 0.67 per 1,000 births. The sex distribution was equal among NTD cases, 55 (48%) females, 59 (51%) males and one (1%) un...
Research Interests: Thailand, Public Health, Folic acid, Humans, Female, and 6 moreMale, Incidence, Cleft Lip, Neural Tube Defects, Birth Defect, and In Utero
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Down Syndrome Parents' Support Group Siriraj Hospital was established on February 14, 1993. It consists of a group of pediatricians, nurses, parents of children with Down Syndrome (DS) who received care at the Genetics Clinic, Division of... more
Down Syndrome Parents' Support Group Siriraj Hospital was established on February 14, 1993. It consists of a group of pediatricians, nurses, parents of children with Down Syndrome (DS) who received care at the Genetics Clinic, Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital. The objective is to educate parents with DS children whose diagnosis of DS given at birth causing grief and disappointment which led to abandonment of these children at Siriraj Hospital almost every other month (fifteen years ago) due to lack of education on the part of the medical professionals. Down Syndrome Parents' Support Group Siriraj Hospital received financial support from Terres des hommes of the Netherlands in the first 6 years. Later it received partial financial support from a government agency; however, the majority of the funding came from private donations. Throughout the years, the group had several successful activities: Siriraj Down Syndrome Annual Meeting since 1991 (total of 17 years) and Down Syndrome Provincial Lecture tour, so called "Down Sunjorn" since 1997. The latest in 2008 (the tenth) which was organized with major provincial hospitals of the Ministry of Public Health (MOPH). Moreover the group took part in (1) working with the Ministry of Education for Thailand Educational Act B.E. 1999 which promotes integration of DS children into normal schools all over the country, (2) working with the Department of Maternal & Child Health, MOPH started the Child Development Center in the provincial community hospitals where the service was lacking; (3) working with Ministry of Social Development' and Human Security to initiate an educational program for the DS families in the rural areas (from 2001 - 2006) to help educate families with DS children and raise awareness for their educational & legal rights. In the past 15 years, there was no more abandonment of DS children at Siriraj Hospital and others; these children received better care and improved quality of life.
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Maternal serum screening has gained widespread acceptance as a major prenatal screening tool for chromosomal abnormalities in the US and Europe since Merkatz et al described an association between low maternal serum alpha fetoprotein... more
Maternal serum screening has gained widespread acceptance as a major prenatal screening tool for chromosomal abnormalities in the US and Europe since Merkatz et al described an association between low maternal serum alpha fetoprotein (AFP) levels and increased risk for trisomy 21 in 1984. In 1988, Wald et al proposed a screening program based on maternal age in combination with three biochemical markers--AFP, hCG and unconjugated estriol. This study from January 1996--September 2002 included 1,793 pregnant women (between 14-22 weeks gestation) which were divided into 2 groups--1,083 women > 35 years (60.40%) and 710 women < 35 years (39.60%). A second trimester risk for trisomy 21 > 1 : 270 was considered a positive screen and genetic counseling to discuss risks and benefits of amniocentesis was offered. This study had 1,376 cases (76.7%) with negative screening (not increased risk for DS and NTD), 21 (1.2%) with negative screening (not increased risk for DS only) ; 292 (16.3%) with increased risk for DS; 5 cases (0.3%) with increased risk for DS and elevated AFP; 19 cases (1.1%) with elevated AFP; 33 cases (1.8%) with previous DS only; and 9 cases (0.5%) with previous NTD only. Two percent (2.1%) of the results could not be interpreted either because the test was done too early, too late or were grand multiple pregnancies. This study demonstrated that multiple marker screening offers another option for older women who traditionally have all been considered candidates for amniocentesis.