Hb Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a rare hemoglobin (Hb) variant due to a mutation at codon 59 of the α2- or α1-globin gene resulting in a glycine to aspartic acid substitution. Two siblings with a unique coinheritance of Hb Adana and Hb Constant Spring (Hb CS, α142, Term→Gln, TAA>CAA; HBA2: c.427 T>C) (α(codon 59)α/α(CS)α), were compared phenotypically with another two siblings carrying the Hb Adana mutation and a 3.7 kb deletion (α(codon 59)α/-α(3.7)). Although they all had α-thalassemia intermedia (α-TI), the former were clinically more severe than the latter. The first pair of siblings presented at a much younger age than the second pair and showed lower Hb levels and significant extramedullay hemopoiesis. Another case of a hydropic fetus as a result of Hb H/Hb Adana is also described. Their clinical phenotypes and hematological parameters are all presented for comparison.
Sickle cell disease (SCD) is an inherited red cell disorder, characterized by the tendency of haemoglobin S or sickle haemoglobin to polymerize and assume a characteristic sickle shape. Molecular analysis has been the mainstay of detection method when confirmation is required. Previously a polymerase chain reaction (PCR)-based restriction enzyme analysis was used for this purpose. A simple bidirectional allele-specific amplification, recently described by Waterfall in 2001 was used to detect the GAG --> GTG mutation on codon 6 of the beta globin gene. Two sets of primers for the mutant and the wild type alleles were used in a single PCR reaction to amplify the regions of interest. The resultant PCR products will produce two fragments at 517 and 267 base pair (bp) respectively. This report highlights the investigations for SCD in the family of a 16-year old girl with recurrent painful crisis affecting the lower limbs whereby the family members are asymptomatic for the disease. Her haemoglobin electrophoresis at an alkaline pH showed dense bands at the HbS and HbF regions, while her father and two sisters had bands at HbS, HbF and HbA. The PCR analysis showed that she was homozygous for the mutation by the presence of only one band at 267 bp fragment, while the father and her sisters were heterozygotes, with the presence of two bands at 267 as well as 517 bp fragments. DNA sequencing of the sample confirmed the mutation. In conclusion, this case report highlighted the simple and cheap yet practical method for molecular confirmation of the presence of HbS gene in subjects with homozygous or heterozygous state of the condition.
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.
OBJECTIVE: The aim of the study was to determine the prevalence of mother-infant bed sharing in Klang district, Peninsular Malaysia and to identify factors associated with bed sharing.
METHOD: This was a cross-sectional study involving 682 mother-infant pairs with infants up to 6 months attending government clinics in Klang district, Peninsular Malaysia. Data were collected by face-to-face interview using a pretested structured questionnaire for a 4-month period in 2006. Data regarding maternal, paternal, obstetric, infant, occupancy, breast-feeding characteristics, and bed-sharing practice were collected. Data on bed sharing were based on practice in the past 1-month period. Bed sharing was defined as an infant sharing a bed with mother, and infant must be within arms reach from the mother, whereas a bed was defined as either a sleeping mattress placed on a bed frame or placed on the floor. The prevalence of bed sharing was estimated. Relationship and magnitude of association between independent factors and bed sharing were examined using odds ratio and 95% confidence interval. Logistic regression analysis was used to control for confounding factors.
RESULTS: The prevalence of bed sharing among mothers with infants aged between 1 and 6 months was 73.5% (95% confidence interval: 70.0-76.7). In multivariate analysis, urban/rural differences, mothers' ethnicity, occupation, family income, husbands' support on bed sharing, number of children younger than 12 years staying in the house, and breast-feeding were associated with bed sharing.
CONCLUSIONS: These factors need to be considered in analyzing the overall risks and benefits of bed sharing, paying attention to breastfeeding practices.
Delayed graft function is a potentially challenging problem especially in cadaveric kidney transplant recipients. It adversely impacts long-term graft survival. It is rarely seen in living kidney transplants. Recovery of graft function usually occurs within a month. The chances of recovery of graft function diminish with further prolongation of delayed function. In fact, recovery of graft function after 3 months has rarely been described, we report herein recovery of graft function after 132 days of nonfunction in a living related kidney transplant.
Infantile neuroaxonal dystrophy 1 (INAD) (OMIM #256600) is a rare infantile onset neurodegenerative disease characterised by neuroregression and hypotonia, evolving into generalized spasticity, blindness and dementia. We report our diagnostic approach of a pair of siblings with psychomotor regression, hypotonia, optic atrophy and auditory neuropathy. The brain magnetic resonance imaging (MRI) showed progressive cerebellar atrophy. Genetic testing of the PLA2G6 confirmed presence of compound heterozygous novel mutations. As the variant c. 196C>T (p.Gln66X) was a truncating variant, it was considered as pathogenic while the variant c. 2249G>A (p. Cys750Tyr) was considered as "likely pathogenic" by bioinformatics analyses. Our patient expands the clinical phenotype of INAD as it described the first South-East Asian patient with INAD-associated auditory neuropathy. Our report highlights the importance of increased awareness of this condition amongst clinicians, the use of deep phenotyping using neuroimaging and the clinical utility of gene sequencing test in the delineation of syndromes associated with infantile neurodegenerative disease.
Introduction: Tobacco smoking is a major public health concern worldwide as it is one of the major risk factors for non-communicable diseases leading to burden of adverse health effects in their later life. According to Global Adult Tobacco Survey Malaysia (2011), 43.9% of men, 1.0% of women, and 23.1% overall currently smoked tobacco. It is important to prevent smoking uptake and promote smoking cessation to reduce the impact of tobacco smoking. The constant monitoring of the magnitude of smoking and its influencing factors is crucial for effective planning of anti-smoking programs. This study aimed to determine the prevalence of smoking and its associated factors among male villagers in Kampung Barambangon, Kudat, Sabah. Methods: A cross-sectional study was conducted among male villagers aged 15 years and above in Kampung Barambangon, Kudat District, Sabah State. Non probability convenience sampling was employed. The study period was from March to April, 2019. Data collection was done by using pretested self-administered questionnaire and a total of 97 villagers were participated in the study. Chi-square test was used for statistical analysis. Results: The study revealed that the prevalence of smokers among male residents in Kampung Barambangon was 50.5% (95% CI: 48.6–52.1%). It was found that there were significant associations between smoking status and positive attitude towards smoking (p-value 0.001), having siblings who smoked (p value 0.001), having high percentage of friends who smoked (p-value 0.009) and high educational level (p-value 0.005). Conclusion: The prevalence of male smokers in Kampung Barambangon was higher than the national prevalence. The findings may help in understanding the magnitude of the smoking problem and its associated factors which can be used for effective tobacco control and intervention programs.
Introduction: Family plays an important role in the development of an adolescent. Several theories postulate in-fluences of bully behaviours within family context. Persistent act of school bullying may lead to violence and eventually disruption of a normal adolescence mental health. This study was done to address whether family factors were associated with school bully perpetrator. Methods: This was a cross sectional study conducted among Form One students from twenty-five schools in Selangor. Parental and respondents’ consents were obtained prior to this research. Data was collected using a self-administered questionnaire comprising of sociodemographic data of the respondents, their family characteristics and parenting style. Cronbach alpha ranged from 0.70- 0.89. Data was analysed using SPSS v25. Ethical approval was obtained from the Ethics Committee for Research Involving Human Subject of Universiti Putra Malaysia (UPM). Results: Response rate was 92.7% with 1221 respondents. Majority of the respondents were females (62%), Malays (82.8%) and lived with married parents (91.2%). Prevalence of bully perpetrator was 12.8%. Parental marital status (p < 0.05), presence of substance abuse among family member (p < 0.05), presence of violence act among family member (p < 0.05), witnessing violence at home (p < 0.05), sibling violence (p < 0.05), presence of family hostility (p < 0.05) and permissive maternal parenting style ( p < 0.05) were associated with school bully perpetrators. Conclusion: This study showed the association between family factors and the development of school bully perpetrators. It is a strong message for parents, educators, policy makers and health providers to collaborate and redesign prevention programmes in an effort to contracept the birth of a school bully.
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) syndrome is a progressive multisystemic neurodegenerative disorder. MELAS syndrome impairs oxidative phosphorylation and predisposes patients to lactic acidosis, particularly under metabolic stress. We report 2 siblings with MELAS-associated idiopathic scoliosis who underwent posterior spinal instrumented fusion with measures taken to minimise anaesthetic and surgical stress, blood loss, and operating time.
The t(11;22) rearrangement is the most common recurrent familial reciprocal translocation in man. Heterozygote carriers are phenotypically normal but are at risk of subfertility in the male, miscarriages, and producing chromosomally unbalanced offspring. The unbalanced progeny usually results from an extra der(22) chromosome resulting from a 3:1 malsegregation. We present here a family with t(11;22). Of six siblings, three were found to be carriers following prenatal diagnosis of the proband fetus. Neither of the two married carrier siblings have a live born child. In keeping with the prevailing knowledge of the pregnancy outcomes of heterozygote carriers, between the siblings they had recurrent miscarriages, a fetus with a +der(22) chromosome, and other subfertility issues resulting in multiple failed in vitro fertilization cycles with preimplantation genetic diagnosis. However, unlike the siblings, their extended family comprising their heterozygote translocation mother, married aunts and an uncle had normal fertility and a lack of a history of miscarriages or an abnormal child. The differing outcomes may be related to the male partners having additional semen anomalies which may further exacerbate problems associated with the t(11;22). Because the t(11;22) rearrangement tends to run in families, it is recommended that chromosome studies are offered to family members of an affected relative as an option, and provide them with appropriate genetic counseling so that they will have the necessary information with regard to their risk for subfertility, miscarriages, and production of viable unbalanced offspring. Follow-up prenatal diagnosis should also be offered to affected expectant family members, especially after preimplantation genetic diagnosis.
Many studies on adolescent smoking have been conducted in Malaysia, but very limited information is available on smoking amongst lower secondary school male students (Forms 1 and 2). We present data from a baseline study in Kota Tinggi District, Johor on the psychosocial factors, stages of smoking acquisition and susceptibility to smoking initiation and their relationship to adolescent smoking. The study is the first wave of a 3-year longitudinal study which was conducted from March 2007 to May 2009, aimed to describe the prevalence of smoking among students in the lower secondary classes. A three stage stratified sampling was performed to obtain a sample. The Bogus Pipeline Method was employed to confirm smoking status. Prevalence of smoking was 35.5%. Smoking prevalence among students of schools located in the Federal Land Development Authority (FELDA) settlement areas (42.9%) was two-fold higher than in the rural and town schools combined (20.29%). Using the Fagerstrom scale, 90% of current smokers had lower addiction to nicotine. Smoking was associated with peer smoking [OR, 4.19 (95% CI, 2.57-6.82)], having a brother smoking [2.17 (1.31-3.61)], parental smoking [1.73 (1.17-2.80)] and locality where respondents attend school [1.94(1.11-3.39)]. The study indicates that, the prevalence of smoking was high in all areas especially FELDA settlement areas. Measures such as teaching of skills to resist social pressure to smoke, establishment of peer support groups and involvement of parents in anti-smoking programs are recommended to curb the high prevalence of smoking among lower secondary school students in Kota Tinggi.
Nesidioblastosis is a rare metabolic disease characterised by inappropriate insulin secretion often associated with life-threatening hypoglycaemia. While severe cases present in the newborn period, patients have been described later in infancy. Familial cases suggest an autosomal recessive trait, and recently mutations in the sulphonlurea receptor gene, possibly a regulator of insulin secretion, have been identified and associated with disease expression. We report a twin boy who developed normally until the age of six months when he was noted to regress. The boy is the older twin born to non-consanguinous parents. He presented to a hospital first at the age of 13 months with fever and generalised seizures. Low blood glucose was noted, but he recovered easily and was able to maintain euglycaemia during a 48-hour period of observation. Microcephaly and developmental delay were documented and anticonvulsant therapy was started. At 18 months, low blood glucose with high C-peptide was documented during reevaluation. Follow-ing a short trial of subcutaneous long-acting somatostatin analogue, the child was subjected to near-total pancreatectomy. The histology revealed findings consistent with nesidioblastosis. The child's condition improved but he remained significantly delayed This case emphasises the importance of recognising and treating hypoglycaemia early to avoid irreversible brain damage. It is interesting to note that the twin brother has always been well and is developmentally normal. Further studies to identify the inheritance pattern in the family would be of great interest.
The exclusive breastfeeding rate in Malaysia is very low. However in recent years the awareness of breastfeeding among mothers has increased. A preliminary qualitative research was carried out on these motivated mothers. The objective of this study was to understand the challenges encountered by breastfeeding mothers and to explore the support and motivation received by them. Information from the motivated mothers was obtained from focus group discussion. Some obstacles faced by the mothers were lack of knowledge on breastfeeding and lack of support from health professionals, parents and siblings. Facilities to express breast milk while at work were not readily available. The main motivation to breastfeed came from the mother herself and support from the husband. A holistic approach must be used to help mothers to continue breastfeeding. This includes breastfeeding promotion and education, setting up more Baby Friendly Hospitals, availability of breastfeeding support groups and provision of enough breastfeeding facilities at work and public places.
A case control study was conducted to identify the risk factors for acute lower respiratory tract infections (ALRI) in hospitalised children in Kelantan. One hun-dred and twenty children aged one month to five years hospitalised for ALRI were matched by age with 120 children as controls. Data on demography and expo-sure to putative risk factors were collected by interview-ing parents or caretakers. Anthropometric measure-ments were also carried out to assess the nutritional sta-tus of the children. For each risk factor studied, the odds ratios for exposure and disease were calculated by using univariate analysis followed by multiple logistic regression analysis to determine those factors which remained significant.
The presence of sibling(s) who coughed at home (OR 12.1, 95% CI 5.2-28.1), crowding in bedroom (OR 4.4, 95% CI 2.1-9.0), weight-for-age < 3rd percentile (OR 9.0, 95% CI 3.1-25.8), lack of breast feeding (OR 9.4, 95% CI 2.3-38.4) and incomplete immunisation (OR 4.5, 95% CI 1.7-12.1) were significant indepen-dent risk factors for ALRI. Other factors like poverty, maternal education level, male sex, low birth weight, history of atopy, family history of asthma and indoor air pollution were not associated with an increased risk of ALRI.
This study showed that poor nutritional status, inap-propriate child care practices and poor living conditions, particularly those related to crowding, predispose to ALRI in Kelantanese children necessitating hospital admission. A change in these factors may reduce the morbidity and mortality of childhood ALRI in Kelantan.
Adolescents are known to obtain information regarding sexual and reproductive health from a variety of sources and not just during formal lessons in schools. This cross-sectional descriptive study was carried out to determine the source of information on sexual and reproductive health among Form four secondary schools girls in the Klang Valley as well as parents’ relationship profile. A total of 520 secondary school girls were recruited for the study. In this study, the source of information on puberty and sexual topics were categorized as follows: first level of importance - mothers, second level of importance - siblings, third level of importance - fathers, fourth level of importance - friends, fifth level of importance - teachers and sixth level of importance - books/internet. A majority of respondents agreed that their mothers were the first level of importance they sought for information on puberty (74.8%) and sexual topics (53.8%). Thirty nine point three percent (39.3%) of respondents reported it was very easy to have a dialogue with their mothers while only 10.0% of the respondents said it was very easy to have a dialogue with their fathers. While this was the case, only 6.3% of the respondents reported discussing sex-related matter with their mothers.
Depressive symptoms exist within the paediatric population. Nonetheless, clear clinical manifestations are often absent in this group. Objective: This study aimed to describe the prevalence and correlates of depressive symptoms among siblings of paediatric outpatients. The outpatients presented for acute complaints only. Methods: This was a cross-sectional study, with data collected over a 16-month period (April 2010 to July 2011). Participants were siblings of paediatric outpatients at University Malaya Medical Centre (UMMC), a tertiary hospital in Kuala Lumpur. They were recruited via convenience sampling. They were classified into high, average and low scores based on their responses to questions in the Children’s Depression Inventory (CDI; T-score >55: high, T-score 45-55: average; Tscore
Study site: paediatric outpatients at University Malaya Medical Centre (UMMC)
On December 26, 2004, an earthquake triggered a devastating tsunami that caused death and destruction in twelve countries including India, Indonesia, Malaysia, Maldives, Seychelles, Somalia, Sri Lanka and Thailand. One of the authors was a volunteer with FELDA WAJA AMAN MALAYSIA medical relief team that served the Aceh victims from 16th February to 24th February 2005 (8 weeks post tsunami). A study to determine the pattern of health ailments was conducted among children aged 18 years and below based at Seuneubok Camp, 30 km from Banda Aceh. All respondents were from Pulau Aceh and the total number of children seen and examined was 60. About 18% had lost their fathers, 10 % had lost their mothers and 27% had lost one or more of their siblings. 77% suffered some form of health ailments. The common health ailments were diarrhea (61%), respiratory complaints (59%) and fever (20%). About 38 % of preschoolers had loss of appetite and 28% had sleep disturbances. About 35% of the elementary school children suffered from sleep disturbances, 29% of the young adolescents suffered from headaches and 24% had sleep disturbances. Nearly a quarter (24%) of all the children felt fearful and anxious about the disaster. Nevertheless, 56% of the respondents wanted to return back to Pulau Aceh, although 14 % did not want to go back. Interestingly, 73% of the children voiced their gratitude to God for having been saved from death.
The thalassaemias are the commonest single gene disorders amongst the inherited diseases. In Malaysia, there are an estimated 2200 transfusion dependent thalassaemia patients. With a carrier rate of 3-5%, 120-340 new cases of thalassaemia are expected to be born each year. The reference treatments for these patients are regular blood transfusions and iron chelation therapy. With optimal management, these patients are able to survive into the third or fourth decade of life and most importantly avoid the complications related to transfusions and iron overload. The use of desferal locally is still limited to only those who can afford i.e. about 30% of the cases. Treatment for some of the complications such as hepatitis C, diabetes mellitus, growth impairment and pubertal delay, are now available. Curative treatment approaches like bone marrow transplantation have now become standard treatment for eligible cases whilst cord blood transplantation may yet offer hope for those who are without compatible sibling donors. Research on globin gene therapy looks very promising but will probably take some time to deliver. Hb F switching is a very novel idea but so far the results are mainly anecdotal. Finally, the strive for optimal management of thalassaemia must come hand in hand with a prevention programme to achieve a reduction of new cases.
Muscular dystrophy is a group of diseases that result in progressive muscle weakness and atrophy. Duchenne Muscular Dystrophy (DMD) is classified as dystrophinopathy and is an X-linked recessive disease. It is caused by alterations in the dystrophin gene at Xp21.2 encoding 79 exons [1]. It is characterised by progressive muscle wasting that begins at 3 to 5 years, delay in motor development and eventually wheelchair confinement followed by premature death at about 30 years from cardiac or respiratory complications [2]. Genetic etiology of cases of DMD in Malaysia are still scarcely reported. Here, we report the genetic cause in the case of an 11-year-old Kelantanese Malay boy who has progressive muscle weakness since 5 years old. He has difficulty in getting up from sitting and supine position also in climbing up stairs until 1st floor. He has a strong family history of DMD and musculoskeletal problems. His younger brother was diagnosed with DMD by molecular analysis and his maternal uncle died at the age of 16 with musculoskeletal problems but was never investigated. Physical examination revealed no dysmorphic features, positive Gower sign with absent tounge fasciculation. On neurological examination, tendon reflexes and muscle tone for limbs were normal. Muscle power for bilateral upper limbs were normal, however, bilateral lower limbs showed slight reduction in muscle power with calf hypertrophy.
Transcription factor 4 (TCF4) gene plays an important role in nervous system development and it always associated with the risk of schizophrenia. Since miRNAs regulate targetgenes by binding to 3'UTRs of target mRNAs, the functional variants located in 3'UTR of TCF4 are highly suggested to affect the gene expressions in schizophrenia. To test the hypothesis regarding the effects of the variants located in 3'UTR of TCF4, we conducted an in silico analysis to identify the functional variants and their predicted functions. In this study, we sequenced the 3'UTR of TCF4 in 13 multiplex schizophrenia families and 14 control families. We found two functional variants carried by three unrelated patients. We determined that the C allele of rs1272363 and the TC insert of rs373174214 might suppress post- transcriptional expression. Secondly, we cloned the region that flanked these two variants into a dual luciferase reporter system and compared the luciferase activities between the pmirGLO-TCF4 (control), pmirGLO-TCF4-rs373174214 and pmirGLO-TCF4-rs1273263. Both pmirGLO-TCF4-rs373174214 and pmirGLO-TCF4-rs1273263 caused lower reporter gene activities, as compared to the control. However, only the C allele of rs1272363 reduced the luciferase activity significantly (p = 0.0231). Our results suggested that rs1273263 is a potential regulator of TCF4 expression, and might be associated with schizophrenia.