Hans Van Rostenberghe

Frequencies of A(TA)7TAA, G71R, and G493R Mutations of the UGT1A1 Gene in the Malaysian Population

Background: Gilbert syndrome is caused by defects in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. These mutations differ among different populations and many of them have been found to be genetic risk factors for the development of neonatal jaundice. Objectives: The objective was to determine the frequencies of the following mutations in the UGT1A1 gene: A(TA)7TAA (the most common cause of Gilbert syndrome in Caucasians), G71R (more common in the Japanese and Taiwanese population), and G493R (described in a homozygous Malay woman with Crigler-Najjar syndrome type 2) in a group of Malaysian babies with hyperbilirubinemia and a group of normal controls. Methods: The GeneScan fragment analysis was used to detect the A(TA)7TAA variant. Mutation screening of both G71R and G493R was performed using denaturing high performance liquid chromatography. Results: Fourteen out of fifty-five neonates with hyperbilirubinemia (25%) carried the A(TA)7TAA mutation (10 heterozygous, 4 homozygous). Seven out of fifty controls (14%) carried this mutation (6 heterozygous, 1 homozygous). The allelic frequencies for hyperbilirubinemia and control patients were 16 and 8%, respectively (p = 0.20). Heterozygosity for the G71R mutation was almost equal among both groups (5.5% for hyperbilirubinemia patients and 6.0% for controls; p = 0.61). One subject (1.8%) in the hyperbilirubinemia group and none of the controls were heterozygous for the G493R mutation (p = 0.476). Conclusions: The A(TA)7TAA seems more common than the G71R and G493R mutations in the Malaysian population.

Screening for G71R mutation of the UGT1A1 gene in the Javanese‐Indonesian and Malay‐Malaysian populations

Abstract Background : There are significant differences in the prevalence and severity of neonatal jaundice among various populations. Recently, it has been reported that a mutation of the UGT1A1 gene, glycine to arginine at codon 71 (G71R), is related to the development of neonatal jaundice in East Asian populations. However, whether the G71R mutation contributes to the high incidence of neonatal jaundice in different Asian populations remains unknown. The authors screened for this mutation in the Javanese‐Indonesian and Malay‐Malaysian populations.

First isolation of Burkholderia tropica from a neonatal patient successfully treated with imipenem.

We report the first case of a human Burkholderia tropica infection. The patient was a premature neonate who had necrotizing enterocolitis with bowel perforation requiring surgical intervention. The stoma care and difficulties in feeding were a chronic problem. At the age of almost 4 months he developed septicemia due to B. tropica. Three consecutive blood cultures grew this organism. The organism was cleared from the blood after a course of imipenem and resolution of post-operative ileus. Our case suggests that environmental and plant pathogens can cause human infection especially in those in an immunocompromised condition.

A polymorphic mutation, c.-3279T > G, in the UGT1A1 promoter is a risk factor for neonatal jaundice in the Malay population.

The uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene encodes the enzyme responsible for bilirubin glucuronidation. To evaluate the contribution of UGT1A1 promoter mutations to neonatal jaundice, we determined the genotypes of c.-3279T>G, c.-3156G>A, and A(TA)7TAA in Malay infants with neonatal jaundice (patients) and in infants without neonatal jaundice (controls). In our population study, only c.-3279T>G was associated with neonatal jaundice. The genotype distributions between both groups were significantly different (p = 0.003): the frequency of homozygosity for c.-3279G was much higher in patients than those in controls. Allele frequency of c.-3279G was significantly higher in patients than those in controls (p = 0.006). We then investigated changes in transcriptional activity because of c.-3279T>G. Luciferase reporter assay in HepG2 cells demonstrated that transcriptional activity of the c.-3279G allele was significantly lower than that of the c.-3279T allele in both the absence and presence of bilirubin. Luciferase reporter assay in COS-7 cells elucidated that c.-3279T>G modified the synergistic effects of the nuclear factors associated with transcriptional machinery. In conclusion, the c.-3279T>G mutation in the UGT1A1 promoter is a genetic risk factor for neonatal jaundice.

Poor correlation between hemolysis and jaundice in glucose 6‐phosphate dehydrogenase‐deficient babies

Abstract Background : The role of hemolysis in the pathophysiology of neonatal jaundice (NNJ) in patients with glucose 6‐phosphate dehydrogenase (G6PD) deficiency has been questioned recently. The aim of the present study was to determine the contribution of hemolysis to the pathophysiology of jaundice in Malay neonates with G6PD deficiency and NNJ.

Comparison of antimicrobial resistance in neonatal and adult intensive care units in a tertiary teaching hospital

Intrahospital variations in antimicrobial profiles may be related to many factors. This study compared causative agents of nosocomial bloodstream infections between a neonatal intensive care unit (NICU) that adopted a ward-tailored antibiotic policy and adult intensive care units (ICUs). Data on organisms from blood cultures obtained from the respective wards between 2005 and 2009 were analyzed. Compared with the adult ICUs, the NICU had a higher frequency of Enterobacteriacae and lower frequencies of typical hospital-acquired pathogens (eg, Klebsiella pneumoniae, 17.4% vs 10.0% [P < .001]; Acinetobacter baumannii, 3.9% vs 11.6% [P < .001]). Antibiotic resistance of gram-negative organisms was also significantly lower in the NICU, including resistance to imipenem (5.7% vs 32.1%; P < .001), amikacin (8.8% vs 30.3%), and ceftriaxone (36.1% vs 74.6%; P < .001). This could possibly be due to the ward-tailored antibiotic policy adopted by the NICU but not by the other ICUs.

High prevalence of Southeast Asian ovalocytosis in Malays with distal renal tubular acidosis

AbstractSoutheast Asian ovalocytosis (SAO) is a red blood cell abnormality common in malaria-endemic regions and caused by a 27 nt deletion of the band 3 protein gene. Since band 3 protein, also known as anion exchanger 1, is expressed in renal distal tubules, the incidence of SAO was examined in distal renal tubular acidosis (dRTA) in Malays in Kelantan, Malaysia. Twenty-two patients with dRTA and 50 healthy volunteers were examined for complication of SAO by both morphological and genetic analyses. SAO was identified in 18 of the 22 dRTA patients (81.8%), but only two of the 50 controls (4%). The incidence of SAO was significantly high in those with dRTA (p<0.001), indicating a dysfunctional role for band 3 protein/anion exchanger 1 in the development of dRTA.

Non-attendance to the paediatric clinics in a Malaysian tertiary hospital: A sizeable problem and identification of an efficacious intervention

Aim:  To determine the rate, causes and risk factors of non‐attendance to the paediatric clinic in a tertiary hospital in Malaysia and to determine the efficacy of one telephone call to confirm a new appointment.

Molecular Heterogeneity of Glucose-6-Phosphate Dehydrogenase Deficiency in Malays in Malaysia

Multiplex polymerase chain reaction (PCR) using multiple tandem forward primers and a common reverse primer (MPTP) was recently established as a comprehensive screening method for mutations in X-linked recessive diseases. In the work reported here, MPTP was used to scan for mutations of the glucose-6-phosphate dehydrogenase (G6PD) gene. Mutations in exons 3, 4, 5, 6, 7, 9, 11, and 12 of the G6PD gene were screened by MPTP in 93 unrelated Malaysian patients with G6PD deficiency. Of the 93 patients, 80 (86%) had identified mutations.Although all of these were missense mutations, identified nucleotide changes were heterogeneous, with 9 mutations involving various parts of the exons. These 9 mutations were G-to-A nucleotide changes at nucleotide 871 of the G6PD gene (G871A), corresponding to G6PD Viangchan, G6PD Mediterranean (C563T), G6PD Vanua Lava (T383C), G6PD Coimbra (C592T), G6PD Kaiping (G1388A), G6PD Orissa (C131G), G6PD Mahidol (G487A), G6PD Canton (G1376T), and G6PD Chatham (G1003A). Our results document heterogeneous mutations of the G6PD gene in the Malaysian population.

Randomised controlled trial of single phototherapy with reflecting curtains versus double phototherapy in term newborns with hyperbilirubinaemia

The use of reflecting curtains with single phototherapy has not yet been directly compared with double phototherapy (DP). The objective of this study is to compare the efficacy of single phototherapy with reflecting curtains (SPRC) and DP in treating neonatal jaundice.