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RANBP2 susceptibility to infection-induced encephalopathy: Clinicoradiologic and molecular description in a Malaysian family

Chew HB, Ngu LH

Mol Genet Metab Rep, 2020 Sep;24:100627.
PMID: 32760653 DOI: 10.1016/j.ymgmr.2020.100627

Pathogenic variants in RANBP2 cause autosomal dominant familial and recurrent Acute Necrotizing Encephalopathy of Childhood (ANEC). Affected children typically experience a 3-stage disease: a 3 to 5 days prodrome of non-specific febrile illness, acute encephalopathy, and recovery with or without neurological sequelae or death. Neuroradiological finding of bilateral symmetrical thalamic lesions raise the suspicion of this diagnosis. A devastating disease, reported mortality approaches 1/3 of those affected and only approximately 10% of patients recover completely without sequelae. We report a Malaysian family with RANBP2 pathogenic variant c.1754C>T (p.Thr585Met). The clinical presentation and course over a maximum of 7 years, as well as neuroradiological features of the 3 affected children are described. In contrast to the reported high mortality and morbidity, our patients have recovered with minor sequelae. We would like to highlight the absence of pathogenic variants in both parents' blood, raising the possibility of germline mosaicism in one of the parents as the underlying genetic mechanism of inheritance. To our knowledge, this is the first report of germline mosaicism in RANBP2 Susceptibility to Infection-induced Encephalopathy.
Fulltext Fourteen new mutations of BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease (MSUD) in Malaysian population

Ali EZ, Ngu LH

Mol Genet Metab Rep, 2018 Dec;17:22-30.
PMID: 30228974 DOI: 10.1016/j.ymgmr.2018.08.006

Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder. This disorder is usually caused by mutations in any one of the genes; BCKDHA, BCKDHB and DBT, which represent E1α, E1β and E2 subunits of the branched-chain α-keto acid dehydrogenase (BCKDH) complex, respectively. This study presents the molecular characterization of 31 MSUD patients. Twenty one mutations including 14 new mutations were identified. The BCKDHB gene was the most commonly affected (45.2%) compared to BCKDHA gene (16.1%) and DBT gene (38.7%). In silico webservers predicted all mutations were disease-causing. In addition, structural evaluation disclosed that all new missenses in BCKDHA, BCKDHB and DBT genes affected stability and formation of E1 and E2 subunits. Majority of the patients had neonatal onset MSUD (26 of 31). Meanwhile, the new mutation; c.1196C > G (p.S399C) in DBT gene was noted to be recurrent and found in 9 patients. Conclusion: Our findings have expanded the mutational spectrum of the MSUD and revealed the genetic heterogeneity among Malaysian MSUD patients. We also discovered the p.S399C from DBT gene was noted as a recurrent mutation in Malay community and it suggested the existence of common and unique mutation in Malay population.
Fulltext Argininosuccinic aciduria: clinical and biochemical phenotype findings in Malaysian children

Chen BC, Ngu LH, Zabedah MY

Malays J Pathol, 2010 Dec;32(2):87-95.
PMID: 21329179 MyJurnal

Argininosuccinic aciduria is an inborn error of the urea cycle caused by deficiency of argininosuccinate lyase (ASL). ASL-deficient patients present with progressive intoxication due to accumulation of ammonia in the body. Early diagnosis and treatment of hyperammonemia are necessary to improve survival and prevent long-term handicap. Two clinical phenotypes have been recognized--neonatal acute and milder late-onset form. We investigated patients with hyperammonemia by a stepwise approach in which quantitative amino acids analysis was the core diagnostic procedure. Here, we describe the clinical phenotypes and biochemical characteristics in diagnosing this group of patients. We have identified 13 patients with argininosuccinic aciduria from 2003 till 2009. Ten patients who presented with acute neonatal hyperammonemic encephalopathy had markedly elevated blood ammonia (> 430 micromol/L) within the first few days of life. Three patients with late-onset disease had more subtle clinical presentations and they developed hyperammonemia only during the acute catabolic state at two to twelve months of age. Their blood ammonia was mild to moderately elevated (> 75-265 micromol/L). The diagnosis was confirmed by detection of excessive levels of argininosuccinate in the urine and/or plasma. They also have moderately increased levels of citrulline and, low levels of arginine and ornithine in their plasma. Two patients succumbed to the disease. To date, eleven patients remained well on a dietary protein restriction, oral ammonia scavenging drugs and arginine supplementation. The majority of them have a reasonable good neurological outcome.
Fulltext Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD): a case with additional features and review of the literature

Chew HB, Ngu LH, Keng WT

BMJ Case Rep, 2011;2011.
PMID: 22715259 DOI: 10.1136/bcr.02.2010.2706

A rare syndrome of rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) has been recently described. We report the first patient with this syndrome in Southeast Asia and review reported cases to date. Our patient was good health with normal development until the age of 2. He then developed hyperphagic obesity, hypersomnolence, seizures, alveolar hypoventilation, central hypothyroidism, sodium and water dysregulation, gastrointestinal dysmotility, strabismus, disordered temperature and irregular heart rate, altered sweating, delayed puberty, mental retardation and recurrent respiratory tract infections. The cardiomyopathy with heart failure and abnormal cerebral spinal fluid (CSF) neurotransmitter analysis present in our patient have not been reported previously. Tumours of the sympathetic nervous system are known to be associated with this syndrome but had not been found in our patient at the time of reporting. We highlight the difficulty of achieving the diagnosis of ROHHAD syndrome and its overlap with other well-established disease entities. The mortality and morbidity resulting from the high incidence of cardiorespiratory arrest may be prevented by early ventilatory support.
Fulltext Identification of mutations in Malaysian patients with argininosuccinate lyase (ASL) deficiency

Ali EZ, Yakob Y, Ngu LH

Mol Genet Metab Rep, 2019 Dec;21:100525.
PMID: 31709144 DOI: 10.1016/j.ymgmr.2019.100525

Argininosuccinate lyase (ASL) deficiency impairs the function of the urea cycle that detoxifies blood ammonia in the body. Mutation that occurs in the ASL gene is the cause of occurrence of ASL deficiency (ASLD). This deficiency causes hyperammonemia, hepatopathy and neurodevelopmental delay in patients. In this study, the clinical characteristics and molecular analysis of 10 ASLD patients were presented. 8 patients were associated with severe neonatal onset, while the other 2 were associated with late onset. Molecular analysis of ASL gene identified four new missense variants, which were c.778C>T, p.(Leu260Arg), c.1340G>C, p.(Ser447Thr), c.436C>G, p.(Arg146Gly) and c.595C>G, p.(Leu199Val) and four reported missense variants, which were c.638G>A, p.(Arg213Gln); c.556C>T, p.(Arg186Trp), c.578G>A, p.(Arg193Gln) and c.436C>G, p.(Arg146Trp). In silico servers predicted all new and reported variants as disease-causing. Structural examination exhibited that all pathogenic variants affected the stability of the tetrameric ASL structure by disturbing the bonding pattern with the neighboring residues.
Conclusion: This study revealed the genetic heterogeneity among Malaysian ASL patients. This study has also expanded the mutational spectrum of the ASL.
Dairy manure pellets and palm oil mill effluent as alternative nutrient sources in cultivating Sporosarcina pasteurii for calcium carbonate bioprecipitation

Omoregie AI, Muda K, Ngu LH

Lett Appl Microbiol, 2022 Jan 14.
PMID: 35032053 DOI: 10.1111/lam.13652

Microbially induced carbonate precipitation (MICP) is a process that hydrolysis urea by microbial urease to fill the pore spaces of soil with induced calcium carbonate (CaCO3 ) precipitates, which eventually results in improved or solidified soil. This research explored the possibility of using dairy manure pellets (DMP) and palm oil mill effluent (POME) as alternative nutrient sources for Sporosarcina pasteurii cultivation and CaCO3 bioprecipitation. Different concentrations (20-80 g l-1 ) of DMP and POME were used to propagate the cells of S. pasteurii under laboratory conditions. The measured CaCO3 contents for MICP soil specimens that were treated with bacterial cultures grown in DMP medium (60%, w/v) was 15·30 ± 0·04 g ml-1 and POME medium (40%, v/v) was 15·49 ± 0·05 g ml-1 after 21 days curing. The scanning electron microscopy showed that soil treated with DMP had rhombohedral structure-like crystals with smooth surfaces, whilst that of POME entailed ring-like cubical formation with rough surfaces Electron dispersive X-ray analysis was able to identify a high mass percentage of chemical element compositions (Ca, C and O), whilst spectrum from Fourier-transform infrared spectroscopy confirmed the vibration peak intensities for CaCO3 . Atomic force microscopy further showed clear topographical differences on the crystal surface structures that were formed around the MICP treated soil samples. These nutrient sources (DMP and POME) showed encouraging potential cultivation mediums to address high costs related to bacterial cultivation and biocementation treatment.
Fulltext Supernumerary derivative (22) syndrome resulting from a maternal balanced translocation

Afroze B, Ngu LH, Roziana A, Aminah M, Noor Shahizan A

Singapore Med J, 2008 Dec;49(12):e372-4.
PMID: 19122939

Supernumerary derivative (22) syndrome is one of the rare genomic syndromes. It is characterised by severe mental retardation, microcephaly, failure to thrive, ear anomalies, preauricular tags or sinus, cleft palate or high arch palate, microganathia, renal anomalies, congenital cardiac defects and genital abnormalities in males. In 99 percent of the cases, one of the parents is a balanced carrier of a translocation between chromosome 11 and chromosome 22. We report the first known case, a female neonate, of supernumerary derivative (22) syndrome from Malaysia.
Fulltext Long-term experience with idursulfase beta (Hunterase) in two adolescent patients with MPS II: A case series

Chan MY, Nelson AJ, Ngu LH

Mol Genet Metab Rep, 2023 Sep;36:100991.
PMID: 37670899 DOI: 10.1016/j.ymgmr.2023.100991

Mucopolysaccharidosis (MPS) type II (Hunter syndrome) is a rare X-linked, recessive, lysosomal storage disorder caused by the deficit of the enzyme iduronate 2-sulfatase (IDS), resulting in accumulation of glycosaminoglycans (GAGs) impairing cellular function in multiple organ systems. Idursulfase (Elaprase, Takeda Pharmaceuticals) and idursulfase beta (Hunterase, GC Biopharma Corp.) are the two currently available enzyme replacement therapies (ERT) for MPS II in Malaysia. ERT in patients with MPS II is associated with improvements in somatic symptoms, pulmonary function, endurance, joint mobility, and quality of life. Though mostly well tolerated, infusion-associated reactions (IARs), such as allergic (IgE-mediated) or nonallergic (non- immunologic) reactions can develop during ERT. In certain cases, when patients develop recurrent IARs despite reduced infusion rate and premedication, either interruption or cessation of ERT might be necessary. However, interruption of ERT is associated with worsening of clinical symptoms such as recurrent respiratory infections, difficulty in standing and walking, and increased joint stiffness, emphasizing the need for continuation of ERT. Here we report successful long-term experience with the use of idursulfase beta in two adolescent Malaysian patients with MPS II, who experienced recurrent infusion-associated reactions warranting discontinuation of ERT with idursulfase.
Oil droplets and solid particles removal using circular separator with inclined coalescence mediums: comparison between co-current and counter-current flow

Ngu LH, Law PL, Wong KK, Yusof AA

Water Sci Technol, 2010;62(5):1129-35.
PMID: 20818055 DOI: 10.2166/wst.2010.407

This research investigated the effects of co- and counter-current flow patterns on oil-water-solid separation efficiencies of a circular separator with inclined coalescence mediums. Oil-water-solid separations were tested at different influent concentrations and flowrates. Removal efficiencies increased as influent flowrate decreased, and their correlationship can be represented by power equations. These equations were used to predict the required flowrate, Q(ss50), for a given influent suspended solids concentration C(iss) to achieve the desired effluent suspended solids concentration, C(ess) of 50 mg/L, to meet environmental discharge requirements. The circular separator with counter-current flow was found to attend removal efficiencies relatively higher as compared to the co-current flow. As compared with co-current flow, counter-current flow Q(ss50) was approximately 1.65 times higher than co-current flow. It also recorded 13.16% higher oil removal at influent oil concentration, C(io) of 100 mg/L, and approximately 5.89% higher TSS removal at all influent flowrates. Counter-current flow's better removal performances were due to its higher coalescing area and constant interval between coalescence plate layers.
Fulltext Biochemical profiling in two siblings with mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency

Ngu LH, Zabedah MY, Shanti B, Teh SH

Malays J Pathol, 2008 Dec;30(2):109-14.
PMID: 19291920 MyJurnal

We report the biochemical profiling in two siblings with mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency. Organic aciduria typical of this rare inborn error metabolism was found when the elder sibling presented with an episode of severe ketoacidosis at 20 months of age, which consisted of excessive excretion of ketones, tiglylglycine, 2-methyl-3-hydroxybutyrate, and 2-methylacetoacetate. Blood acylcarnitiness profile showed elevation of C5OH-carnitine, which represents 2-methyl-3-hydroxybutyrylcarnitine. A similar biochemical profile was identified in the younger sibling during screening although he had only mild clinical symptoms. Both patients reported a favourable outcome on follow-up.
Fulltext Clinical and biochemical profiles of maple syrup urine disease in malaysian children

Yunus ZM, Kamaludin DA, Mamat M, Choy YS, Ngu L

JIMD Rep, 2012;5:99-107.
PMID: 23430924 DOI: 10.1007/8904_2011_105

INTRODUCTION: Maple Syrup Urine Disease (MSUD) is an autosomal recessive disorder caused by defects in the branched-chain α-ketoacid dehydrogenase complex resulting in accumulation of branched-chain amino acids (BCAAs) and corresponding branched-chain ketoacids (BCKAs) in tissues and plasma, which are neurotoxic. Early diagnosis and subsequent nutritional modification management can reduce the morbidity and mortality. Prior to 1990s, the diagnosis of MSUD and other inborn errors of metabolism (IEM) in Malaysia were merely based on clinical suspicion and qualitative one-dimensional thin layer chromatography technique. We have successfully established specific laboratory diagnostic techniques to diagnose MSUD and other IEM. We described here our experience in performing high-risk screening for IEM in Malaysia from 1999 to 2006. We analysed the clinical and biochemical profiles of 25 patients with MSUD.
METHODS: A total of 12,728 plasma and urine samples from patients suspected of having IEM were received from physicians all over Malaysia. Plasma amino acids quantitation using fully automated amino acid analyzer and identification of urinary organic acids using Gas Chromatography Mass Spectrometry (GCMS). Patients' clinical information were obtained from the request forms and case records Results: Twenty-five patients were diagnosed MSUD. Nineteen patients (76%) were affected by classical MSUD, whereas six patients had non-classical MSUD. Delayed diagnosis was common among our case series, and 80% of patients had survived with treatment with mild-to-moderate learning difficulties.
CONCLUSION: Our findings suggested that MSUD is not uncommon in Malaysia especially among the Malay and early laboratory diagnosis is crucial.
Fulltext Case report of treatment experience with idursulfase beta (Hunterase) in an adolescent patient with MPS II

Ngu LH, Ong Peitee W, Leong HY, Chew HB

Mol Genet Metab Rep, 2017 Sep;12:28-32.
PMID: 28540187 DOI: 10.1016/j.ymgmr.2017.05.002

Mucopolysaccharidosis (MPS) II or Hunter syndrome is a chronic, progressive, multi-systemic illness associated with significant morbidity and early mortality. Available evidence in Asian populations shows that Hunter syndrome has a mean age of onset of 2 to 5 years and a life expectancy of 13 years in more severely affected individuals, with respiratory failure reported as the leading cause of death. Enzyme replacement therapy (ERT) with idursulfase (Elaprase, Shire Pharmaceuticals) and idursulfase beta (Hunterase, Green Cross Corp) are the only approved treatment for patients with MPS II. While these agents have the same amino acids, they have different glycosylation patterns because they are produced in different cell lines via different manufacturing processes. In previous studies, the beneficial effects of idursulfase beta have been confirmed in patients up to 35 years of age, without serious treatment-related safety concerns. The major drawbacks associated with ERT include the potential development of serious infusion-related anaphylactic reactions and up to 50% of treated patients develop anti-IDS antibodies. Here we report the case of a 13-year-old Malaysian patient with attenuated MPS II who developed troublesome infusion-associated reactions while receiving idursulfase treatment but tolerated and responded favorably to idursulfase beta.
Fulltext Molybdenum cofactor deficiency in a Malaysian child

Ngu LH, Afroze B, Chen BC, Affandi O, Zabedah MY

Singapore Med J, 2009 Oct;50(10):e365-7.
PMID: 19907877

Molybdenum cofactor deficiency is a rare autosomal recessive disorder with devastating neurological manifestations, characterised by neonatal-onset encephalopathy mimicking hypoxic-ischaemic insult, intractable seizure, and feeding and respiratory difficulties. It is often fatal in the early life. We report an affected 8-year-old boy, who presented with severe neurological manifestations since birth, but without clinically-significant seizure. Molybdenum cofactor deficiency must be included in the differential diagnosis of patients presenting with unexplained encephalopathy in the newborn period, and whose neuroimaging findings are consistent with hypoxic ischaemic encephalopathy. The classic laboratory hallmark of this disorder is low serum uric acid, positive urine sulphite dipstick test, and elevated urinary S-sulphocysteine, hypoxanthine and xanthine.
Fulltext Mowat-Wilson syndrome: the first two Malaysian cases

Balasubramaniam S, Keng WT, Ngu LH, Michel LG, Irina G

Singapore Med J, 2010 Mar;51(3):e54-7.
PMID: 20428734

Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation; a multiple congenital anomaly syndrome characterised by a typical facial gestalt, Hirschsprung disease or severe constipation, genitourinary anomaly, congenital heart defects, agenesis of corpus callosum and eye defects. Some cases also present with epilepsy, growth retardation with microcephaly and speech impairment. MWS was first described in 1998 by Mowat et al, and approximately 180 cases have been reported as of August 2008. The syndrome occurs as a result of heterozygous mutations or deletions in the zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1). Most cases reported so far were sporadic occurrences; however, rare cases of sibling recurrence have been cited. The facial phenotype is particularly important for the initial clinical diagnosis and provides the hallmark, warranting ZEB2 mutational analysis even in the absence of Hirschsprung disease. We present the first two molecularly confirmed Malaysian MWS patients, one of whom has a novel mutation.
Fulltext Separation of sulfated urinary glycosaminoglycans by high-resolution electrophoresis for isotyping of mucopolysaccharidoses in Malaysia

Nor A, Zabedah MY, Norsiah MD, Ngu LH, Suhaila AR

Malays J Pathol, 2010 Jun;32(1):35-42.
PMID: 20614724

Mucopolysaccharidoses (MPS) are a group of inherited disorders caused by the deficiency of specific lysosomal enzymes involved in glycosaminoglycans (GAGs) degradation. Currently, there are 11 enzyme deficiencies resulting in seven distinct MPS clinical syndromes and their subtypes. Different MPS syndromes cannot be clearly distinguished clinically due to overlapping signs and symptoms. Measurement of GAGs content in urine and separation of GAGs using high-resolution electrophoresis (HRE) are very useful initial screening tests for isotyping of MPS before specific enzyme diagnostics. In this study, we measured total urinary GAGs by a method using dimethylmethylene blue (DMB), and followed by isolation and separation of GAGs using high resolution electrophoresis (HRE) technique. Of 760 urine samples analyzed, 40 have abnormal GAGs HRE patterns. Thirty-five of these 40 cases have elevated urinary GAGs levels as well. These abnormal HRE patterns could be classified into 4 patterns: Pattern A (elevated DS and HS; suggestive of MPS I, II or VII; 16 cases), Pattern B (elevated HS and CS; suggestive of MPS III; 17 cases), and Pattern C (elevated KS and CS; suggestive of MPS IV, 5 cases), and Pattern D (elevated DS; suggestive of MPS VI; 2 cases). Based on the GAGs HRE pattern and a few discriminating clinical signs, we performed selective enzymatic investigation in 16 cases. In all except one case with MPS VII, the enzymatic diagnosis correlated well with the provisional MPS type as suggested by the abnormal HRE pattern. Our results showed that GAGs HRE is a useful, inexpensive and practical first-line screening test when MPS is suspected clinically, and it provides an important guide to further enzymatic studies on a selective basis.
Neonatal intrahepatic cholestasis associated with citrin deficiency (NICCD): a case series of 11 Malaysian patients

Chew HB, Ngu LH, Zabedah MY, Keng WT, Balasubramaniam S, Hanifah MJ, et al.

J Inherit Metab Dis, 2010 Dec;33 Suppl 3:S489-95.
PMID: 21161389 DOI: 10.1007/s10545-010-9248-6

Citrin deficiency, aetiologically linked to mutations of SLC25A13 gene, has two clinical phenotypes, namely adult-onset type II citrullinaemia (CTLN2) and neonatal/infantile intrahepatic cholestasis, caused by citrin deficiency (NICCD). Malaysian patients with NICCD, especially of Malay and East Malaysian indigenous descent, have never been reported in the literature. We present the clinical features, biochemical findings and results of molecular analysis in 11 Malaysian children with NICCD. In this case series, all patients manifested prolonged cholestatic jaundice and elevated citrulline levels. The other more variable features included failure to thrive, bleeding diathesis, hypoproteinaemia, abnormal liver enzymes, prolonged coagulation profile, hyperammonaemia, hypergalactosaemia, multiple aminoacidaemia, elevated α-feto protein and urinary orotic acid as well as liver biopsies showing hepatitis and steatosis. DNA analysis of SLC25A13 revealed combinations of 851del4(Ex9), IVS16ins3kb and 1638ins23. Most of our patients recovered completely by the age of 22 months. However, one patient had ongoing symptoms at the time of reporting and one had died of liver failure. Since a small percentage of children with NICCD will develop CTLN2 and the mechanisms leading to this is yet to be defined, ongoing health surveillance into adulthood is essential.
Fulltext Selective screening for detection of mucopolysaccharidoses in Malaysia; A two-year study (2014-2016)

Omar A, Jalil JA, Shakrin NM, Ngu LH, Yunus ZM

Mol Genet Metab Rep, 2019 Jun;19:100469.
PMID: 31193155 DOI: 10.1016/j.ymgmr.2019.100469

Introduction: Mucopolysaccharidoses (MPS) are a group of inherited disorders caused by the deficiency of a specific lysosomal enzyme involved in glycosaminoglycans (GAGs) degradation. This enzyme deficiency leads to accumulation of GAGs in the lysosomes, resulting in organ dysfunction and enlargement. We aimed to detect cases of MPS in patients with suggestive signs and symptoms.
Methods: This was a 2-year cross-sectional study conducted during June 2014 to May 2016. Urine and whole blood samples were taken from high-risk MPS patients. All urine samples were analysed for GAGs and characterised by high resolution electrophoresis (HRE). Whole blood was collected in ethylenediaminetetraacetic acid (EDTA) tube and analysed for specific enzymes based on the clinical history and HRE findings.
Results: From the 60 samples tested, 15 were positive for MPS; (Type I = 1), (Type II = 4), (Type IIIA = 3), (Type IVA = 1), (Type VI = 6). The overall prevalence of MPS among high-risk Malaysian patients was 26% (95% CI 14.72% to 37.86%). One patient had mucolipidosis. The mean age of patients when diagnosed was 5 years old. Patients with MPS were more likely to present with hepatosplenomegaly compared to other symptoms (OR = 0.974, p 
Fulltext Demographic, laboratory findings and diagnostic evaluation among high risk patients with mucopolysaccharidosis in Malaysia

Omar A, Jalil JA, Shakrin NM, Ngu LH, Yunus ZM

Data Brief, 2019 Aug;25:104377.
PMID: 31516928 DOI: 10.1016/j.dib.2019.104377

This article contains information related to a recent study "Selective screening for detection of mucopolysaccharidoses (MPS) in Malaysia; A Two-year Study" Affandi et al., 2019. Any patient registered under government healthcare facilities in Malaysia and fit at least two inclusion criteria were included in this selective screening. Urine and blood from these high risk patients were obtained and analysed for glycosaminoglycans (GAGs) level before characterization using high resolution electrophoresis (HRE). Thereafter, enzyme assay for different types of MPS based on result of HRE were determined using specific substrate. Demographic data as well as laboratory findings were tabulated and analysed. The data of this study demonstrate between clinical presentation and laboratory findings among high risk patients of MPS and can be employed to improve diagnosis of MPS.
Intron retention is among six unreported AGL mutations identified in Malaysian GSD III patients

Abdullah IS, Teh SH, Khaidizar FD, Ngu LH, Keng WT, Yap S, et al.

Genes Genomics, 2019 08;41(8):885-893.
PMID: 31028654 DOI: 10.1007/s13258-019-00815-9

BACKGROUND: Glycogen storage disease type III is an autosomal recessive disorder that is caused by deficiencies of the glycogen debranching enzyme. Mutations within the AGL gene have been found to be heterogeneous, with some common mutations being reported in certain populations. The mutation spectrum of AGL gene in the multi-ethnic Malaysian population is still unknown.
OBJECTIVE: The present study seeks to determine the mutation spectrum of the AGL gene in Malaysian population.
METHODS: A total of eleven patients (eight Malay, two Chinese and one Bajau) were investigated. Genomic DNA was extracted and subsequently the AGL gene was amplified using specific primers and sequenced. Mutations found were screened in 150 healthy control samples either by restriction enzyme digestion assay or TaqMan® SNP Genotyping assay.
RESULTS: We identified six unreported mutations (c.1423+1G>T, c.2914_2915delAA, c.3814_3815delAG, c.4333T>G, c.4490G>A, c.4531_4534delTGTC) along with three previously reported mutations (c.99C>T, c.1783C>T, c.2681+1G>A). One of the six unreported mutation causes abnormal splicing and results in retention of intron 12 of the mature transcript, while another is a termination read-through. One of the reported mutation c.2681+1G>A was recurrently found in the Malay patients (n = 7 alleles; 31.8%).
CONCLUSION: The mutation spectrum of the AGL gene in Malaysian patients has shown considerable heterogeneity, and all unreported mutations were absent in all 150 healthy control samples tested.
Novel heterozygous mutations in TALDO1 gene causing transaldolase deficiency and early infantile liver failure

Balasubramaniam S, Wamelink MM, Ngu LH, Talib A, Salomons GS, Jakobs C, et al.

J Pediatr Gastroenterol Nutr, 2011 Jan;52(1):113-6.
PMID: 21119539 DOI: 10.1097/MPG.0b013e3181f50388

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