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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*
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*
Hyperexcretion of homocitrulline in a Malaysian patient with lysinuric protein intolerance

Habib A, Md Yunus Z, Azize NA, Ch'ng GS, Ong WP, Chen BC, et al.

Eur J Pediatr, 2013 Sep;172(9):1277-81.
PMID: 23358709 DOI: 10.1007/s00431-013-1947-1

Lysinuric protein intolerance (LPI; MIM 222700) is an inherited aminoaciduria with an autosomal recessive mode of inheritance. Biochemically, affected patients present with increased excretion of the cationic amino acids: lysine, arginine, and ornithine. We report the first case of LPI diagnosed in Malaysia presented with excessive excretion of homocitrulline. The patient was a 4-year-old male who presented with delayed milestones, recurrent diarrhea, and severe failure to thrive. He developed hyperammonemic coma following a forced protein-rich diet. Plasma amino acid analysis showed increased glutamine, alanine, and citrulline but decreased lysine, arginine and ornithine. Urine amino acids showed a marked excretion of lysine and ornithine together with a large peak of unknown metabolite which was subsequently identified as homocitrulline by tandem mass spectrometry. Molecular analysis confirmed a previously unreported homozygous mutation at exon 1 (235 G > A, p.Gly79Arg) in the SLC7A7 gene. This report demonstrates a novel mutation in the SLC7A7 gene in this rare inborn error of diamino acid metabolism. It also highlights the importance of early and efficient treatment of infections and dehydration in these patients.
CONCLUSION: The diagnosis of LPI is usually not suspected by clinical findings alone, and specific laboratory investigations and molecular analysis are important to get a definitive diagnosis.

Matched MeSH terms: Amino Acid Metabolism, Inborn Errors/genetics
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*
Fulltext Neonatal intrahepatic cholestasis caused by citrin deficiency in two Malaysian siblings: outcome at one year of life

Thong MK, Boey CC, Sheng JS, Ushikai M, Kobayashi K

Singapore Med J, 2010 Jan;51(1):e12-4.
PMID: 20200759

We report two Malaysian siblings with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). The younger sibling, a six-month-old Chinese girl, presented with prolonged neonatal jaundice, and was investigated for biliary atresia. Urine metabolic screen showed the presence of urinary-reducing sugars, and she was treated with a lactose-free formula. NICCD was suspected based on the clinical history, examination and presence of urinary citrulline. Mutation study of the SLC25A13 gene showed the compound heterozygotes, 851del4 and IVS16ins3kb, which confirmed the diagnosis of NICCD in the patient and her three-year-old female sibling, who also had unexplained neonatal cholestasis. Long-term dietary advice, medical surveillance and genetic counselling were provided to the family. The diagnosis of NICCD should be considered in infants with unexplained prolonged jaundice. DNA-based genetic testing of the SLC25A13 gene may be performed to confirm the diagnosis retrospectively. An awareness of this condition may help in early diagnosis using appropriate metabolic and biochemical investigations, thus avoiding invasive investigations in infants with neonatal cholestasis caused by NICCD.

Matched MeSH terms: Metabolism, Inborn Errors/genetics*
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*
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
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
Matched MeSH terms: Metabolism, Inborn Errors/genetics*
Succinic Semialdehyde Dehydrogenase Deficiency in a Chinese Boy: A Novel ALDH5A1 Mutation With Severe Phenotype

Tay CG, Ariffin H, Yap S, Rahmat K, Sthaneshwar P, Ong LC

J Child Neurol, 2015 Jun;30(7):927-31.
PMID: 25122112 DOI: 10.1177/0883073814540523

Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessive disorder affecting catabolism of the neurotransmitter gamma-aminobutyric acid (GABA), with a wide range of clinical phenotype. We report a Malaysian Chinese boy with a severe early onset phenotype due to a previously unreported mutation. Urine organic acid chromatogram revealed elevated 4-hydroxybutyric acid. Magnetic resonance imaging (MRI) of the brain demonstrated cerebral atrophy with atypical putaminal involvement. Molecular genetic analysis showed a novel homozygous 3-bp deletion at the ALDH5A1 gene c.1501_1503del (p.Glu501del). Both parents were confirmed to be heterozygotes for the p.Glu501del mutation. The clinical course was complicated by the development of subdural hemorrhage probably as a result of rocking the child to sleep for erratic sleep-wake cycles. This case illustrates the need to recognize that trivial or unintentional shaking of such children, especially in the presence of cerebral atrophy, can lead to subdural hemorrhage.

Matched MeSH terms: Amino Acid Metabolism, Inborn Errors/genetics*
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/genetics
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/genetics*