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Identification of a Novel IGSF1 Variant in Two Malaysian Male Siblings with Central Hypothyroidism and Macroorchidism

Lee YL, Ting TH, Lim CT, Thilakavathy K, Musa NH, Ling KH

J Clin Res Pediatr Endocrinol, 2024 Apr 22.
PMID: 38647408 DOI: 10.4274/jcrpe.galenos.2024.2023-12-1

IGSF1 mutation is the commonest cause of mild to moderate isolated central congenital hypothyroidism and has an X-linked recessive inheritance, primarily affecting males. Other notable clinical features are macroorchidism with delayed pubertal testosterone rise, large birth weight, increased body mass index, low prolactin, transient growth hormone deficiency and low prolactin. Two male siblings with central hypothyroidism were found to have a novel IGSF1 c.3467T>A variant that was likely pathogenic based on the family segregation study. The proband, aged 3 years presented at 18 days old with prolonged jaundice while his 16-year-old brother was only detected to have central hypothyroidism after the proband's genetic analysis result was known. Both siblings were obese, had large birth weights, macroorchidism and low prolactin. The proband's brother had intellectual disability while the proband had normal development. This case study highlights the importance of evaluation for the IGSF1 variant in patients with unexplained central hypothyroidism, especially when accompanied by X-linked inheritance and macroorchidism. Family segregation analysis allows detection of other affected family members or carriers who may also benefit from thyroxine treatment.
Fulltext The significance of tubular and glomerular proteinuria in critically ill patients with severe acute kidney injury

Lim CT, Tan HK, Lau YK

Pak J Med Sci, 2014 Nov-Dec;30(6):1186-90.
PMID: 25674105 DOI: 10.12669/pjms.306.5684

Critically ill patients with acute kidney injury (AKI) frequently need acute renal replacement therapy (aRRT). We evaluated an inexpensive, rapid quantitative and qualitative analysis of proteinuria on the course of AKI patients requiring aRRT in intensive care.
Fulltext Risk profiles of referred chronic kidney disease patients in a tertiary nephrology centre

Lim CT, R R, A S MZ

Pak J Med Sci, 2016 Mar-Apr;32(1):27-30.
PMID: 27022339 DOI: 10.12669/pjms.321.8214

OBJECTIVES: The aims of this study were to determine the seroprevalence of acute dengue in Universiti Kebangsaan Malaysia (UKM) Medical Centre and its correlation with selected haematological and biochemical parameters.
METHODS: This cross-sectional study was conducted from January to June 2015. A patient was serologically diagnosed with acute dengue if the dengue virus IgG, IgM or NS-1 antigen was reactive.
RESULTS: Out of 1,774 patients suspected to have acute dengue, 1,153 were serologically diagnosed with the infection, resulting in a seroprevalence of 64.9%. Dengue-positive patients had a lower mean platelet count (89 × 10(9)/L) compared to the dengue-negative patients (171 × 10(9)/L) (p<0.0001). The mean total white cell count was also lower in the dengue-positive cases (4.7 × 10(9)/L vs. 7.2 × 10(9)/L; p<0.0001). The mean haematocrit was higher in patients with acute dengue (42.5% vs. 40.0%; p<0.0001). Likewise, the serum alanine transaminase level was also higher in patients with acute dengue (108 U/L vs. 54 U/L; p<0.0001).
CONCLUSIONS: Dengue is very prevalent in UKM Medical Centre as most patients suspected to have acute dengue had serological evidence of the infection. The platelet count was the single most likely parameter to be abnormal (i.e. low) in patients with acute dengue.
KEYWORDS: DENV; Dengue; IgG; IgM; NS1; Seroprevalence
Fulltext Predictor of cardiovascular risks in end stage renal failure patients on maintenance dialysis

Lim CT, Yap XH, Chung KJ, Khalid MA, Yayha N, Latiff LA, et al.

Pak J Med Sci, 2015 Nov-Dec;31(6):1300-5.
PMID: 26870086 DOI: 10.12669/pjms.316.8039

OBJECTIVE: Cardiovascular disease (CVD) is the main cause of morbidity and premature mortality in end stage renal failure patients (ESRD) receiving dialysis. The aim of our study was to evaluate the impact of various risk factors in this group of high CVD risk patients in local population.
METHODS: We carried out a cross-sectional retrospective study in a single hospital. A total of 136 ESRF patients, consisted of 43 haemodialysis (HD) and 93 continuous ambulatory peritoneal dialysis (CAPD) patients, were recruited and followed up for 36 months duration. Midweek clinical and laboratory data were collected. The occurrence of existing and new CVD events was recorded.
RESULTS: Multiple Logistic Regression showed pre-existing cardiovascular event (odds ratio, 4.124; 95% confidence interval [CI], 0.990 to 17.187), elevated total cholesterol level (odds ratio, 0.550; 95% CI, 0.315 to 0.963), elevated serum phosphate level (odds ratio, 5.862; 95% CI, 1.041 to 33.024) and elevated random blood glucose level (odds ratio, 1.193; 95% CI, 1.012 to 1.406) were significantly associated with occurrence of CVD events.
CONCLUSIONS: History of cardiovascular event before the initiation of dialysis, elevated level of serum phosphate and random blood glucose levels are the risk factors of CVD whereas paradoxically a high total cholesterol level has CVD protective effect towards the ESRF patients.
KEYWORDS: CVD risk; End Stage Renal Failure (ESRF); Haemodialysis; Peritoneal dialysis
Treatment decisions in severely ill newborns

Lim CT

Med J Malaysia, 2000 Aug;55 Suppl B:17-22.
PMID: 11125515
Group B streptococcus: maternal carriage rate and early neonatal septicaemia

Lim CT, Thong MK, Parasakthi N, Ngeow YF

Ann Acad Med Singap, 1997 Jul;26(4):421-5.
PMID: 9395802

Between January 1984 and December 1994, 30 cases of early neonatal group B streptococcus (GBS) septicaemia were managed in the Neonatal Unit, University Hospital, Kuala Lumpur. Two neonates were outborn and 28 were inborn, giving an average annual incidence of neonatal GBS septicaemia of 0.4/1000 livebirths among inborn babies. In a separate survey over a three-month period, GBS genital carriage rate among 196 parturients was found to be 9.7%. Of the infants with GBS septicaemia, the mean gestational age was 37.5 +/- 3.8 weeks and the mean birthweight was 2540 +/- 716 g. Twelve (40%) were preterm infants and 14 (47%) were low birthweight infants. Male and female infants were almost equally affected. Prolonged rupture of membranes and maternal pyrexia accounted for only 5 (17%) and 3 (10%) of the cases respectively. Twenty-four (80%) neonates had onset of symptoms within 6 hours of life and respiratory symptoms were observed in 24 (80%) of the cases, while meningitis was uncommon. Six (20%) neonates died. Preterm and low birthweight infants had higher mortality than their term counterparts: 42% versus 6% and 36% versus 6% respectively. Of those who died, 4 (67%) required respiratory support right from birth and the mean time of onset of symptoms was 4 hours (range 0 to 21 hours) and the duration of survival was only 28.8 hours (range 12 to 38 hours). As the incidence of neonatal GBS septicaemia was low, mass screening and chemoprophylaxis for GBS were not recommended. All the GBS isolates were sensitive to penicillin and ampicillin, thus one of these antibiotics should be included in the antimicrobial therapy of septic neonates.
Fulltext Early congenital syphilis--a continuing problem in Malaysia

Lim CT, Koh MT, Sivanesaratnam V

Med J Malaysia, 1995 Jun;50(2):131-5.
PMID: 7565181

Between February 1990 and May 1993, 13 cases of early congenital syphilis (ECS) were managed in the Paediatrics Unit, University Hospital, Kuala Lumpur. Twelve mothers were unbooked with 10 inborn babies. Only one mother had antenatal booking at this hospital but she defaulted antenatal follow-up. Several risk factors associated with ECS were identified: inadequate or no prenatal care (5/13), failure to repeat a serological test for syphilis in the third trimester when it was tested negative at first booking (5/13), sexual promiscuity, substance abuse and a past history of contracting sexually transmitted disease. All 10 mothers who had their serological test repeated at delivery were found to have a positive VDRL and TPHA. Adequate antenatal care early referral of infected, expectant mothers for treatment, and a repeat serological test for syphilis could have prevented these cases of ECS.
Bilateral ovarian cysts in a newborn: a case report

Lim CT, Wong KK, Yap YF, Sivanesaratnam V

Asia Oceania J Obstet Gynaecol, 1992 Mar;18(1):19-22.
PMID: 1627057

Large ovarian cysts in the fetus are uncommon. Ultrasonography has helped in the detection of these cysts antenatally and in the newborn female infant. A case of bilateral ovarian cysts in a newborn is presented. The choice of management between conservative measures and surgical approaches remains controversial.
Oculopharyngeal muscular dystrophy: a case report and a review of literature

Lim CT, Chew CT, Chew SH

Ann Acad Med Singap, 1992 May;21(3):399-403.
PMID: 1416791

Most muscular dystrophies manifest as peripheral muscular weakness commencing at various age, however, oculopharyngeal muscular dystrophy (OPMD) is a rare hereditary disorder presenting in middle age with progressive dysphagia and bilateral blepharoptosis rather than peripheral muscular weakness. In the medical literature, OPMD has been well described in Canadians of French descent. So far, there is no publication of OPMD in the Malaysia-Singapore medical literature. This article documents this condition in a Chinese patient. A review of the literature is presented and the management of OPMD is discussed.
Cerebro-costo-mandibular syndrome

Lim CT, Koh MT

Australas Radiol, 1992 May;36(2):158-9.
PMID: 1520180

Cerebro-costo-mandibular syndrome (CCM) is a very rare entity with oro-facial features closely resembling Pierre-Robin anomaly (1,2). We describe a patient with typical features: severe micrognathia, glossoptosis, central cleft soft palate and multiple posterior rib-gap defects seen on chest radiograph. Respiratory distress which was evident soon after birth was relieved by an oro-pharyngeal airway. He suffered from a cardiorespiratory arrest and succumbed, presumably secondary to aspiration of milk feeds, before a tracheostomy could be performed.
Depressed skull fracture in a newborn successfully managed conservatively: a case report

Lim CT, Koh MT, Sivanesaratnam V

Asia Oceania J Obstet Gynaecol, 1991 Sep;17(3):227-9.
PMID: 1953432

A preterm baby was born to a multiparous mother by emergency caesarean section at 36 weeks of gestation. Apart from a depression on the right temporo-parietal region measuring 3 cm x 3 cm x 0.5 cm, no other abnormality was noted. A CT scan of the brain excluded the presence of intracranial haematoma and pressure effect on the brain. Spontaneous reduction of the fracture without any adverse neurological sequelae suggests that these fractures can be managed conservatively in some instances.
Resolution of rare palatal brown tumour after parathyroidectomy

Lim CT, Thevandran TK

Clin Exp Nephrol, 2017 Apr;21(2):352-353.
PMID: 27339441 DOI: 10.1007/s10157-016-1292-6
Fulltext Meconium ileus--a rare cause of neonatal intestinal obstruction in Malaysia

Lim CT, Yip CH, Chang KW

Singapore Med J, 1994 Feb;35(1):74-6.
PMID: 8009287

Meconium ileus, rare in Malaysia, accounts for 3.7% of all neonatal intestinal obstructions (excluding imperforate anus) seen in the University Hospital, Kuala Lumpur, from 1980-1990. This paper retrospectively reviews our clinical experience with 5 cases of meconium ileus seen over a 12-year period from 1980-1991 in the University Hospital, Kuala Lumpur. Three of the neonates were Malays, and two were Punjabis. Four of them were full-term and one preterm. The birth weights ranged from 1900 to 3700 g, with a mean of 2670 g. One of them also had a sibling with meconium ileus. Two of them were found to have foetal ascites and one had intestinal obstruction, antenatally by ultrasonography. The remaining two were symptomatic soon after birth. Extensive calcification was observed on plain abdominal radiographs in three babies and dilated bowels in the other two. All of them underwent laparotomy and uncomplicated meconium ileus was confirmed in two cases, meconium peritonitis in two and one meconium pseudocyst in addition to meconium peritonitis. There was one intraoperative death, and one long-term survivor who did not have cystic fibrosis. The remaining three did not have additional features suggestive of cystic fibrosis, and finally succumbed to respiratory infection. Sweat test was not done to confirm the diagnosis for logistic reasons. The management of such patients proved to be a challenge to clinicians because of the rarity of this condition.
Fulltext Neonatal meningitis due to non-encapsulated Haemophilus influenzae in a set of twins--a case report

Lim CT, Parasakthi N, Puthucheary SD

Singapore Med J, 1994 Feb;35(1):104-5.
PMID: 8009266

A set of twins born to a 24-year-old primigravida had evidence of sepsis 24 to 60 hours after birth and were treated empirically with penicillin and gentamicin. A non-encapsulated H. influenzae biotype IV strain was isolated from the blood cultures of both and from the CSF of twin II. The isolates were beta-lactamase positive and hence showed resistance to ampicillin and therapy was changed to chloramphenicol only. Twin II recovered but Twin I developed a brain abscess in the left occipital region which resolved with extended antibiotic treatment. Although ampicillin-resistant H. influenzae have been reported in Malaysia, invasive disease by such strains are rare.
Fulltext Severe metabolic changes following oral sodium phosphate in a patient of renal cell carcinoma - On dialysis

Lim CT

Indian J Pharmacol, 2016 May-Jun;48(3):327-8.
PMID: 27298508 DOI: 10.4103/0253-7613.182875

Oral sodium phosphate (OSP), an effective bowel purgative, is available over the counter (OTC) and requires a substantially lower volume than polyethylene glycol-based preparative agents. Rarely, OSP consumption has been associated with acute hypocalcemia and hyperphosphatemia. We describe a case of chronic kidney disease patient developing symptomatic hypocalcemia following OTC OSP.
Fulltext The effectiveness of surfactant replacement therapy for preterm infants with respiratory distress syndrome

Lim WL, Lim CT, Chye JK

Med J Malaysia, 1998 Dec;53(4):376-84.
PMID: 10971981

Thirty preterm infants weighing > or = 800 g with clinical and radiological evidence of respiratory distress syndrome (RDS) requiring mechanical ventilation with FiO2 of > or = 40% were given modified bovine surfactant (Survanta). They were compared with equal number of historical controls. Infants who received surfactant showed prompt and highly significant improvement in FiO2, mean airway pressure, arterial/alveolar oxygen tension ratio and ventilatory index. There was significant improvement in mortality rate (10% vs 33%; p = 0.03). Among the survivors, surfactant-treated infants required shorter duration of continuous positive airway pressure (CPAP) (3.4 vs 9.6 days; p = 0.04). For survivors with birthweight of > 1000 g, surfactant-treated infants required shorter duration of ventilatory support (intermittent positive pressure ventilation + CPAP) (7.5 vs 18.9 days, p = 0.02). Overall, surfactant-treated infants achieved full enteral feeds sooner (15.7 days vs 24.6 days; p = 0.03) and required shorter duration of total parenteral nutrition (13.9 days vs 25.6 days; p = 0.02). We concluded that surfactant replacement therapy was effective in the treatment of preterm infants with RDS.
Quality of life in dialysis: A Malaysian perspective

Liu WJ, Musa R, Chew TF, Lim CT, Morad Z, Bujang A

Hemodial Int, 2014 Apr;18(2):495-506.
PMID: 26820998 DOI: 10.1111/hdi.12108

There is a growing interest to use quality of life as one of the dialysis outcome measurement. Based on the Malaysian National Renal Registry data on 15 participating sites, 1569 adult subjects who were alive at December 31, 2012, aged 18 years old and above were screened. Demographic and medical data of 1332 eligible subjects were collected during the administration of the short form of World Health Organization Quality of Life questionnaire (WHOQOL-BREF) in Malay, English, and Chinese language, respectively. The primary objective is to evaluate the quality of life among dialysis patients using WHOQOL-BREF. The secondary objective is to examine significant factors that affect quality of life score. Mean (SD) transformed quality of life scores were 56.2 (15.8), 59.8 (16.8), 58.2 (18.5), 59.5 (14.6), 61.0 (18.5) for (1) physical, (2) psychological, (3) social relations, (4) environment domains, and (5) combined overall quality of life and general health, respectively. Peritoneal dialysis group scored significantly higher than hemodialysis group in the mean combined overall quality of life and general health score (63.0 vs. 60.0, P
Fulltext Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination

Lo YL, van Hasselt JG, Heng SC, Lim CT, Lee TC, Charles BG

Antimicrob Agents Chemother, 2010 Jun;54(6):2626-32.
PMID: 20385872 DOI: 10.1128/AAC.01370-09

The present study determined the pharmacokinetic profile of vancomycin in premature Malaysian infants. A one-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration data (n = 835 points) obtained retrospectively from the drug monitoring records of 116 premature newborn infants. Vancomycin concentrations were estimated by a fluorescence polarization immunoassay. Population and individual estimates of clearance and distribution volume and the factors which affected the variability observed for the values of these parameters were obtained using a population pharmacokinetic modeling approach. The predictive performance of the population model was evaluated by visual inspections of diagnostic plots and nonparametric bootstrapping with replacement. Dosing guidelines targeting a value of > or =400 for the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC(24)/MIC ratio) were explored using Monte Carlo simulation. Body size (weight), postmenstrual age, and small-for-gestational-age status are important factors explaining the between-subject variability of vancomycin pharmacokinetic parameter values for premature neonates. The typical population parameter estimates of clearance and distribution volume for a 1-kg premature appropriate-for-gestational-age neonate with a postmenstrual age of 30 weeks were 0.0426 liters/h and 0.523 liters, respectively. There was a 20% reduction in clearance for small-for-gestational-age infants compared to the level for the appropriate-for-gestational-age control. Dosage regimens based on a priori target response values were formulated. In conclusion, the pharmacokinetic parameter values for vancomycin in premature Malaysian neonates were estimated. Improved dosage regimens based on a priori target response values were formulated by incorporating body size, postmenstrual age, and small-for-gestational-age status, using Monte Carlo simulations with the model-estimated pharmacokinetic parameter values.
Speech stimuli and nasalance scores for the assessment of resonance in in Mandarin speaking Malaysian children

Mohd Ibrahim H, Lim HW, Ahmad Rusli Y, Lim CT

Clin Linguist Phon, 2020 06 02;34(6):554-565.
PMID: 31537131 DOI: 10.1080/02699206.2019.1668480

This study was designed to develop language-specific stimuli for the assessment of resonance and to obtain nasalance scores using the newly developed speech stimuli in Mandarin. Gender and age influences on nasalance scores for each of the stimulus were also examined. Participants recruited were typically developing Mandarin-speaking ethnic Chinese children aged 6;00-7;11 growing up in Malaysia. Perceptual ratings of nasality were made based on the GOS.SP.ASS.'98 (revised) for children while nasalance scores were recorded for each stimulus using the Nasometer II (Model 6400). Fifty Mandarin-speaking children (24 males and 26 females) were recruited. None of the participants were perceived with abnormal nasality on the three stimuli. The mean nasalance scores for the Mandarin stimuli were 16.08% (SD = 2.57, 95% CI = 15.35-16.81) for the Oral passage, 25.20% (SD = 3.63, 95% CI = 24.17-26.23) for the Oral-Nasal passage and 55.44% (SD = 4.17, 95% CI = 54.25-56.63) for the Nasal passage. No significant age- and gender-related differences were observed for all the three stimuli. This is the first set of Mandarin stimuli and nasalance norms for Mandarin-speaking children in Malaysia. The influence of phonetic content on nasalance is supported. Findings call for language-specific normative nasalance data and careful selection of stimuli for the assessment of resonance.
Fulltext Targeted Oxygen in the Resuscitation of Preterm Infants, a Randomized Clinical Trial

Oei JL, Saugstad OD, Lui K, Wright IM, Smyth JP, Craven P, et al.

Pediatrics, 2017 01;139(1).
PMID: 28034908 DOI: 10.1542/peds.2016-1452

BACKGROUND AND OBJECTIVES: Lower concentrations of oxygen (O2) (≤30%) are recommended for preterm resuscitation to avoid oxidative injury and cerebral ischemia. Effects on long-term outcomes are uncertain. We aimed to determine the effects of using room air (RA) or 100% O2 on the combined risk of death and disability at 2 years in infants <32 weeks' gestation.
METHODS: A randomized, unmasked study designed to determine major disability and death at 2 years in infants <32 weeks' gestation after delivery room resuscitation was initiated with either RA or 100% O2 and which were adjusted to target pulse oximetry of 65% to 95% at 5 minutes and 85% to 95% until NICU admission.
RESULTS: Of 6291 eligible patients, 292 were recruited and 287 (mean gestation: 28.9 weeks) were included in the analysis (RA: n = 144; 100% O2: n = 143). Recruitment ceased in June 2014, per the recommendations of the Data and Safety Monitoring Committee owing to loss of equipoise for the use of 100% O2. In non-prespecified analyses, infants <28 weeks who received RA resuscitation had higher hospital mortality (RA: 10 of 46 [22%]; than those given 100% O2: 3 of 54 [6%]; risk ratio: 3.9 [95% confidence interval: 1.1-13.4]; P = .01). Respiratory failure was the most common cause of death (n = 13).
CONCLUSIONS: Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks' gestation. This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably. Additional data are needed.

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