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  1. A negative waveform in the scotopic response in a patient with phosphoglycerate kinase deficiency: a visual electrophysiology report
    Mohd Khialdin S, Grigg J, Rowe N, Crofts S, Wilson M, Troedson C
    Documenta ophthalmologica. Advances in ophthalmology, 2015 Dec;131(3):215-20.
    PMID: 26396085 DOI: 10.1007/s10633-015-9511-0
    Phosphoglycerate kinase (PGK) deficiency is an X-linked neurometabolic genetic disorder with variable systemic manifestations. So far, only one patient with retinal anomalies has been reported, but no visual electrophysiology findings were described. We report the first description of visual electrophysiology in a child with PGK deficiency. This provides further information for the site of involvement in the eye.
    Matched MeSH terms: Metabolism, Inborn Errors/genetics; Metabolism, Inborn Errors/physiopathology*
  2. Fulltext A new nested allele-specific multiplex polymerase chain reaction method for haplotyping of VKORC1 gene to predict warfarin sensitivity
    Chua YA, Abdullah WZ, Yusof Z, Gan SH
    Biomed Res Int, 2014;2014:316310.
    PMID: 24790995 DOI: 10.1155/2014/316310
    The vitamin K epoxide reductase complex 1 gene (VKORC1) is commonly assessed to predict warfarin sensitivity. In this study, a new nested allele-specific multiplex polymerase chain reaction (PCR) method that can simultaneously identify single nucleotide polymorphisms (SNPs) at VKORC1 381, 861, 5808, and 9041 for haplotype analysis was developed and validated. Extracted DNA was amplified in the first PCR DNA, which was optimized by investigating the effects of varying the primer concentrations, annealing temperature, magnesium chloride concentration, enzyme concentration, and the amount of DNA template. The amplification products produced from the first round of PCR were used as templates for a second PCR amplification in which both mutant and wild-type primers were added in separate PCR tubes, followed by optimization in a similar manner. The final PCR products were resolved by agarose gel electrophoresis and further analysed by using a VKORC1 genealogic tree to infer patient haplotypes. Fifty patients were identified to have H1H1, one had H1H2, one had H1H7, 31 had either H1H7 or H1H9, one had H1H9, eight had H7H7, and one had H8H9 haplotypes. This is the first method that is able to infer VKORC1 haplotypes using only conventional PCR methods.
    Matched MeSH terms: Metabolism, Inborn Errors/genetics*
  3. A rational approach to infant feeding in the management of sugar intolerance associated with infantile enteritis
    Chua CP
    Med J Malaysia, 1975 Dec;30(2):98-101.
    PMID: 1228389
    Matched MeSH terms: Carbohydrate Metabolism, Inborn Errors/complications*
  4. A tribute to Keiko Kobayashi and her work on citrin deficiency
    Thong MK
    Mol Genet Metab, 2012 Apr;105(4):551-2.
    PMID: 22284267 DOI: 10.1016/j.ymgme.2012.01.003
    Matched MeSH terms: Metabolism, Inborn Errors/etiology*; Metabolism, Inborn Errors/history*
  5. Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations
    Chen BC, McGown IN, Thong MK, Pitt J, Yunus ZM, Khoo TB, et al.
    J Inherit Metab Dis, 2010 Dec;33 Suppl 3:S159-62.
    PMID: 20177786 DOI: 10.1007/s10545-010-9056-z
    Most cases of adenylosuccinate lyase (ADSL OMIM 103050) deficiency reported to date are confined to the various European ethnic groups. We report on the first Malaysian case of ADSL deficiency, which appears also to be the first reported Asian case. The case was diagnosed among a cohort of 450 patients with clinical features of psychomotor retardation, global developmental delay, seizures, microcephaly and/or autistic behaviour. The patient presented with frequent convulsions and severe myoclonic jerk within the first few days of life and severe psychomotor retardation. The high performance liquid chromatography (HPLC) profile of the urine revealed the characteristic biochemical markers of succinyladenosine (S-Ado) and succinyl-aminoimidazole carboximide riboside (SAICAr). The urinary S-Ado/SAICAr ratio was found to be 1.02 (type I ADSL deficiency). The patient was compound heterozygous for two novel mutations, c.445C > G (p.R149G) and c.774_778insG (p.A260GfsX24).
    Matched MeSH terms: Purine-Pyrimidine Metabolism, Inborn Errors/complications; Purine-Pyrimidine Metabolism, Inborn Errors/diagnosis*; Purine-Pyrimidine Metabolism, Inborn Errors/enzymology; Purine-Pyrimidine Metabolism, Inborn Errors/genetics*
  6. Fulltext An Improved Oil Palm Genome Assembly as a Valuable Resource for Crop Improvement and Comparative Genomics in the Arecoideae Subfamily
    Ong AL, Teh CK, Mayes S, Massawe F, Appleton DR, Kulaveerasingam H
    Plants (Basel), 2020 Nov 03;9(11).
    PMID: 33152992 DOI: 10.3390/plants9111476
    Oil palm (Elaeis guineensis Jacq.) is the most traded crop among the economically important palm species. Here, we report an extended version genome of E. guineensis that is 1.2 Gb in length, an improvement of the physical genome coverage to 79% from the previous 43%. The improvement was made by assigning an additional 1968 originally unplaced scaffolds that were available publicly into the physical genome. By integrating three ultra-dense linkage maps and using them to place genomic scaffolds, the 16 pseudomolecules were extended. As we show, the improved genome has enhanced the mapping resolution for genome-wide association studies (GWAS) and permitted further identification of candidate genes/protein-coding regions (CDSs) and any non-coding RNA that may be associated with them for further studies. We then employed the new physical map in a comparative genomics study against two other agriculturally and economically important palm species-date palm (Phoenix dactylifera L.) and coconut palm (Cocos nucifera L.)-confirming the high level of conserved synteny among these palm species. We also used the improved oil palm genome assembly version as a palm genome reference to extend the date palm physical map. The improved genome of oil palm will enable molecular breeding approaches to expedite crop improvement, especially in the largest subfamily of Arecoideae, which consists of 107 species belonging to Arecaceae.
    Matched MeSH terms: Lipid Metabolism, Inborn Errors
  7. Fulltext An inhibited dopamine synthesizing cell model of AADC deficiency
    Melati Khalid, Mohamad Aris Mohd Moklas
    Life Sciences, Medicine and Biomedicine, 2019;3(2):1-7.
    MyJurnal
    Aromatic L-amino acid decarboxylase deficiency (AADC) is a rare autosomal recessive pediatric neurotransmitter disease. To date it remains poorly understood mainly due to an absence of a disease model. The dopaminergic neuroblastoma cell SH-SY5Y was chosen to develop our AADC deficiency model. These cells are not native dopamine synthesizers. Objective: To develop a dopamine-producing cellular model of AADC deficiency using SH-SY5Y neuroblastoma cells. Methods: Dopamine pathway proteins were identified with Western Blotting. Dopaminergic differentiation was attempted using all-trans retinoic acid (ATRA) with dopamine detection via HPLC-ECD post alumina extraction. Treatment with L-DOPA provided SH-SY5Y with excess precursor. RT-PCR was used to determine the expression of markers of mature neurons. Results: Western Blot screening identified AADC, dopamine β-hydroxylase and tyrosine hyrdoxylase proteins, indicative of a dopaminergic pathway. ATRA was unsuccessful in producing dopamine from the cells. L-DOPA treatment however, generated dopamine first visible as a HPLC-ECD peak 30 minutes post-incubation. Prior to this, SH-SY5Y dopamine synthesis from L-DOPA has never been documented. This de novo synthesis is then inhibited using benserazide to form our AADC deficiency cell model. RT-PCR showed that SH-SY5Y cells express markers of mature neurons in its ‘native’ state and is not affected by L-DOPA and benserazide treatment. This cell model will potentially benefit many areas of AADC deficiency research. Conclusion: SH-SY5Y cells produced HPLC-ECD measureable amounts of dopamine with the addition of L-DOPA. Our model of AADC deficiency is generated by quelling the dopamine production with Benserazide.
    Matched MeSH terms: Amino Acid Metabolism, Inborn Errors
  8. Analysis of the breath hydrogen test for carbohydrate malabsorption: validation of a pocket-sized breath test analyser
    Lee WS, Davidson GP, Moore DJ, Butler RN
    J Paediatr Child Health, 2000 Aug;36(4):340-2.
    PMID: 10940167
    OBJECTIVE: To assess the validity and clinical application of a hand-held breath hydrogen (H2) analyzer (BreatH2, Europa Scientific, Crewe, UK).

    METHODOLOGY: Breath samples of patients referred to the Gastroenterology Unit, Women's and Children's Hospital, North Adelaide, South Australia, for confirmation of the diagnosis of carbohydrate malabsorption were analysed with the Quintron microlyzer (Quintron Instrument Co., Milwaukee, USA) and the BreatH2 analyser, using the Quintron microlyzer as the gold standard.

    RESULTS: Twenty-nine breath H2 tests (BHT) were performed in 29 patients aged 2 months to 61 years. The sensitivity and specificity of the BreatH2 analyser in detecting a positive BHT using the Quintron microlyser as the gold standard were 0.90 and 0.95 with positive and negative predictive values of 0.90 and 0.95, respectively. There was one false positive and one false negative reading. Bland-Altman plots showed a high degree of agreement between the values obtained with two different methods.

    CONCLUSIONS: The diagnosis of carbohydrate malabsorption, using a portable breath H2 analyser (BreatH2), achieved an acceptable degree of sensitivity and specificity, enabling it to be used where no alternative is available.

    Matched MeSH terms: Carbohydrate Metabolism, Inborn Errors/diagnosis*
  9. Beta-ketothiolase deficiency in a Malaysian infant
    Rajan D, Constance LSL, Brandon P
    Med J Malaysia, 2019 04;74(2):174-175.
    PMID: 31079130
    Methylacetoacetyl-coenzyme A thiolase (MAT) deficiency is an autosomal recessive disease caused by a defect of mitochondrial acetoacetyl-CoA thiolase (T2). There is an error of isoleucine catabolism and ketone body utilization due to mutations in the acetyl-Coenzyme A acetyltransferase 1 (ACAT1) gene. We report a case of a 14 months old Sabahan boy with beta deficiency who presented with severe sepsis and ketoacidosis who subsequently recovered.
    Matched MeSH terms: Amino Acid Metabolism, Inborn Errors/complications; Amino Acid Metabolism, Inborn Errors/diagnosis*; Amino Acid Metabolism, Inborn Errors/genetics
  10. Fulltext Biochemical and molecular characteristics of Malaysian patients with lysinuric protein intolerance
    Habib A, Azize NA, Yakob Y, Md Yunus Z, Wee TK
    Malays J Pathol, 2016 Dec;38(3):305-310.
    PMID: 28028301 MyJurnal
    Lysinuric protein intolerance (LPI) is an inborn error of dibasic amino acid transport due to a defect in the dibasic amino acid transporter in the renal and intestine and has a heterogenous presentation. Three Malaysian patients with LPI were studied and their biochemical and molecular findings compared. There were differences and similarities in the biochemical and molecular findings. Molecular analysis of SLC7A7 gene revealed a novel mutation c.235G>A; p.(Gly79Arg) in exon three in Patient 1 and a mutation c.1417C>T; p.(Arg473*) in exon 10 in patient 2 and 3. The degree of concentration of dibasic amino acids may determine the type of disease of the cell membrane transport, however, a positive molecular confirmation will secure the diagnosis.
    Matched MeSH terms: Amino Acid Metabolism, Inborn Errors/genetics*
  11. 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.
    Matched MeSH terms: Metabolism, Inborn Errors/physiopathology*; Metabolism, Inborn Errors/urine*
  12. Fulltext Cerebrotendinous xanthomatosis with cholestanolaemia--involvement of five individuals in a Malay family
    Othman NH, Rahman SA
    Med J Malaysia, 1990 Dec;45(4):275-80.
    PMID: 2152046
    Cerebrotendinous xanthomatosis (CTX), a rare inherited lipid storage disease is due to a defect in bile acid metabolism. Involvement of five members of a family is presented. The clinical features, laboratory and pathologic findings are discussed. Tendinous and tuberous xanthomatosis, bilateral cataracts, cerebral impairment and raised serum cholestanol are the salient features. We believe this is the first report of CTX in Malaysia.
    Matched MeSH terms: Lipid Metabolism, Inborn Errors/genetics*; Lipid Metabolism, Inborn Errors/pathology
  13. Fulltext Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1
    Abdul Wahab SA, Yakob Y, Abdul Azize NA, Md Yunus Z, Huey Yin L, Mohd Khalid MK, et al.
    Biomed Res Int, 2016;2016:4074365.
    PMID: 27672653
    Glutaric aciduria type 1 (GA1) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase enzyme encoded by the GCDH gene. In this study, we presented the clinical and molecular findings of seven GA1 patients in Malaysia. All the patients were symptomatic from infancy and diagnosed clinically from large excretion of glutaric and 3-hydroxyglutaric acids. Bidirectional sequencing of the GCDH gene revealed ten mutations, three of which were novel (Gln76Pro, Glu131Val, and Gly390Trp). The spectrum of mutations included eight missense mutations, a nonsense mutation, and a splice site mutation. Two mutations (Gln76Pro and Arg386Gln) were homozygous in two patients with parental consanguinity. All mutations were predicted to be disease causing by MutationTaster2. In conclusion, this is the first report of both clinical and molecular aspects of GA1 in Malaysian patients. Despite the lack of genotype and phenotype correlation, early diagnosis and timely treatment remained the most important determinant of patient outcome.
    Matched MeSH terms: Amino Acid Metabolism, Inborn Errors
  14. Clinical, biochemical, and molecular overview of transaldolase deficiency and evaluation of the endocrine function: Update of 34 patients
    Williams M, Valayannopoulos V, Altassan R, Chung WK, Heijboer AC, Keng WT, et al.
    J Inherit Metab Dis, 2019 01;42(1):147-158.
    PMID: 30740741 DOI: 10.1002/jimd.12036
    BACKGROUND: Transaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype-genotype correlation.

    METHODS: We performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. In some patients, endocrine abnormalities have been found. To further evaluate these abnormalities, we performed biochemical investigations on blood of 14 patients.

    RESULTS AND CONCLUSIONS: Most patients (n = 22) had an early-onset presentation (prenatally or before 1 month of age); 12 patients had a late-onset presentation (3 months to 9 years). Main presenting symptoms were intrauterine growth restriction, dysmorphic facial features, congenital heart disease, anemia, thrombocytopenia, and hepato(spleno)megaly. An older sib of two affected patients was asymptomatic until the age of 9 years, and only after molecular diagnosis was hepatomegaly noted. In some patients, there was gonadal dysfunction with low levels of testosterone and secondary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) abnormalities later in life. This overview provides information that can be helpful for managing patients and counseling families regarding prognosis. Diagnostic guidelines, possible genotype-phenotype correlations, treatment options, and pathophysiological disease mechanisms are proposed.

    Matched MeSH terms: Carbohydrate Metabolism, Inborn Errors/genetics*; Carbohydrate Metabolism, Inborn Errors/metabolism*
  15. Clinical, biochemical, and molecular overview of transaldolase deficiency and evaluation of the endocrine function: update of 34 patients
    Williams M, Valayannopoulos V, Altassan R, Chung WK, Heijboer AC, Keng WT, et al.
    J Inherit Metab Dis, 2018 May 02.
    PMID: 29721915 DOI: 10.1007/s10545-018-0184-1
    BACKGROUND: Transaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype-genotype correlation.

    METHODS: We performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. In some patients, endocrine abnormalities have been found. To further evaluate these abnormalities, we performed biochemical investigations on blood of 14 patients.

    RESULTS AND CONCLUSIONS: Most patients (n = 22) had an early-onset presentation (prenatally or before 1 month of age); 12 patients had a late-onset presentation (3 months to 9 years). Main presenting symptoms were intrauterine growth restriction, dysmorphic facial features, congenital heart disease, anemia, thrombocytopenia, and hepato(spleno)megaly. An older sib of two affected patients was asymptomatic until the age of 9 years, and only after molecular diagnosis was hepatomegaly noted. In some patients, there was gonadal dysfunction with low levels of testosterone and secondary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) abnormalities later in life. This overview provides information that can be helpful for managing patients and counseling families regarding prognosis. Diagnostic guidelines, possible genotype-phenotype correlations, treatment options, and pathophysiological disease mechanisms are proposed.

    Matched MeSH terms: Carbohydrate Metabolism, Inborn Errors
  16. Fulltext Complete mitochondrial genome of Bactrocera arecae (Insecta: Tephritidae) by next-generation sequencing and molecular phylogeny of Dacini tribe
    Yong HS, Song SL, Lim PE, Chan KG, Chow WL, Eamsobhana P
    Sci Rep, 2015;5:15155.
    PMID: 26472633 DOI: 10.1038/srep15155
    The whole mitochondrial genome of the pest fruit fly Bactrocera arecae was obtained from next-generation sequencing of genomic DNA. It had a total length of 15,900 bp, consisting of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding region (A + T-rich control region). The control region (952 bp) was flanked by rrnS and trnI genes. The start codons included 6 ATG, 3 ATT and 1 each of ATA, ATC, GTG and TCG. Eight TAA, two TAG, one incomplete TA and two incomplete T stop codons were represented in the protein-coding genes. The cloverleaf structure for trnS1 lacked the D-loop, and that of trnN and trnF lacked the TΨC-loop. Molecular phylogeny based on 13 protein-coding genes was concordant with 37 mitochondrial genes, with B. arecae having closest genetic affinity to B. tryoni. The subgenus Bactrocera of Dacini tribe and the Dacinae subfamily (Dacini and Ceratitidini tribes) were monophyletic. The whole mitogenome of B. arecae will serve as a useful dataset for studying the genetics, systematics and phylogenetic relationships of the many species of Bactrocera genus in particular, and tephritid fruit flies in general.
    Matched MeSH terms: Amino Acid Metabolism, Inborn Errors
  17. Fulltext Congenital renal anomalies - a dissection observational study
    Bilodi, Arun Kumar .S, Gangadhar, M R
    Malaysian Journal of Medical Research, 2017;1(1):14-18.
    MyJurnal
    Anomaly is a congenital disorder. It is a medical condition that is present since birth. But the word congenital neither applies nor excludes genetic disorder. Congenital anomalies due to environmental factors are called as Teratogens. Infections, deficiency in the diet and toxins are environmental causes. Maternal folic acid deficiency may cause spina bifida. Intake of alcohol, and certain prescribed drugs like phenytoin may cause congenital anomalies or defects. Apart from physical anomalies, other types of congenital disorders are inborn errors of metabolism (Kumar, Abbas and Fausto, 2005). About 15% to 25% of anomalies are due to chromosomal factors or single gene factors, 8% to 12% anomalies are said to be due to environmental factors, 25% are said to be due to multifactorial inheritance 40% to 60% of anomalies are of unknown origin (Stevenson, 1993 ; Nelson and Holmes, 1984). Congenital anomalies are present since birth with structural deformity found immediately after birth or their presence may be detected by signs and symptoms later on (Holland and Brew, 1991). Congenital Anomalies are seen in 2% of population as major abnormality. There are two types of abnormalities, namely malformations where growth disturbances occur during embryogenesis and the other is deformation. It is late change that appears in a structure which was normal earlier (Roizen and Patterson, 2003).
    Matched MeSH terms: Metabolism, Inborn Errors
  18. Diaphroase activity and variants in normal adults and newborns
    Eng LI, Loo M, Fah FK
    Br J Haematol, 1972 Oct;23(4):419-25.
    PMID: 5084807
    Matched MeSH terms: Metabolism, Inborn Errors/enzymology
  19. Fatty liver in a two days old neonate
    Arivalagan P, Husain MS, Subramaniam K, Kaslan MRM
    Med J Malaysia, 2019 Oct;74(5):454-455.
    PMID: 31649231
    Neonatal death due to inborn error of metabolism (IEM) is rare in Malaysia. We report a sudden neonate death just a few hours after being discharged from the hospital. The deceased was a two-day-old baby boy and was asymptomatic until his demise. He was fed with expressed breast milk and formula milk. Autopsy revealed fatty changes of the liver and an enlarged heart. Laboratory investigation confirmed very long chain Acyl-CoA dehydrogenase deficiency which resulted in his death. Autopsy of sudden unexpected death in neonate should include investigation for inborn error of metabolism. Fatty liver and enlarged heart could give a clue for the diagnosis.
    Matched MeSH terms: Lipid Metabolism, Inborn Errors
  20. Fulltext Genes, medicine and society: from paediatrics to genetic counselling and beyond
    Thong MK
    JUMMEC, 2012;15(2):1-8.
    MyJurnal
    The story of clinical genetics is a relatively new one, first spearheaded by paediatrics but increasingly, has taken root in all branches of medicine leading to ‘personalised medicine’. There are expectations that this revolution in genetics will pave the way to genomic medicine and a cure for all inherited disorders. The development of the field of Clinical Genetics and genetic counselling in Malaysia is still in its infancy. Using evidence-based data on genetic disorders such as birth defects, inborn errors of metabolism, genetic syndromes, neurological disorders and hereditary cancers, that hitherto have not been well documented in Malaysia, this review article will focus on findings and issues that will present a unique insight and opportunity to understanding the complex genetic counselling issues related to clinical genetics in Malaysia.
    Matched MeSH terms: Metabolism, Inborn Errors
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