A study was carried out of 332 babies suffering from severe neonatal jaundice who were admitted to the General Hospital, Kuala Lumpar, Malaysia. Of the 332 neonates, 51 were premature and 281 were full-term babies, 178 (110 Chinese, 58 Malay, 9 Indian and 1 European-Pakistani) had bilirubin levels of 20 mg% or higher, requiring exchange blood transfusion. Of the Chinese neonates, 23 (20.9%) had G6PD deficiency, 9 (8.2%) had Hb Bart's and 2 (1.8%) had an abnormal haemoglobin, one Hb Q and one fetal variant. Among the Malay infants, 10 (17.2%) had G6PD deficiency, 7 (12.1%) had Hb Bart's and 10 (17.2%) had abnormal haemoglobins (four had Hb E trait, one had Hb K and Bart's in addition to Hb E, three had Hb CoSp with Hb Bart's, one had Hb Q and one Hb Tak). One of the nine Indian neonates had G6PD deficiency and one had Hb S trait. The one European-Pakistani baby was a carrier of Hb D Punjab. In addition to G6PD deficiency, abnormal haemoglobins seem to have contributed to the high incidence of severe neonatal jaundice in Malaysia. The mean activities of GP, GR and GR after stimulation with FAD were higher, while the mean activity of PK and mean level of reduced glutathione were lower than in normal cord bloods. The percent increase of GR after FAD stimulation was significantly lower; fewer in this group had increases above 20% than in normal cord blood. The possible significance of the findings is discussed.
The Malaysian people consist of several ethnic groups including the Malay, the Chinese, the Indian and the Orang Asli (aboriginal Malaysians). We collected blood samples from outpatients of 2 hospitals in the State of Selangor and identified 27 glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects among these ethnic groups. In the Malay, G6PD Viangchan (871GA, 1311CT, IVS11 nt93TC) and G6PD Mahidol (487GA) types, which are common in Cambodia and Myanmar, respectively, were detected. The Malay also had both subtypes of G6PD Mediterranean:the Mediterranean subtype (563CT, 1311CT, IVS11 nt93TC) and the Indo-Pakistan subtype (563CT, 1311C, IVS11 nt93T). In Malaysians of Chinese background, G6PD Kaiping (1388GA), G6PD Canton (1376GT) and G6PD Gaohe (95AG), which are common in China, were detected. Indian Malaysians possessed G6PD Mediterranean (Indo-Pakistan subtype) and G6PD Namoru (208TC), a few cases of which had been reported in Vanuatu and many in India. Our findings indicate that G6PD Namoru occurs in India and flows to Malaysia up to Vanuatu. We also discovered 5 G6PD-deficient cases with 2 nucleotide substitutions of 1311CT and IVS11 nt93TC, but without amino-acid substitution in the G6PD molecule. These results indicate that the Malaysian people have incorporated many ancestors in terms of G6PD variants.
Study site: Kajang District Hospital and the Hospital Orang Asli Gombak, Selangor, Malaysia
A three day old male, term infant with hemothorax due to hemorrhagic disease of the newborn was treated successfully with vitamin K and thoracocentesis. Exclusive breast feeding and absence of vitamin K prophylaxis were important diagnostic clues, although hemothorax as a sole manifestation of hemorrhagic disease of the newborn is rare. This case highlighted the good prognosis of an uncommon complication when prompt diagnosis and appropriate treatment are instituted. The importance of vitamin K prophylaxis to all newborns is emphasized.
Matched MeSH terms: Vitamin K Deficiency Bleeding/complications*; Vitamin K Deficiency Bleeding/therapy
Iron deficiency is prevalent in childhood in the developed and developing countries. Programs of presumptive therapy, mass supplementation and food fortification have been introduced in many countries. The unresolved debate over the interaction of iron and infection in the clinical setting prompts re-evaluation of these practices. Situations of iron overload are associated with increased susceptibility to certain infections, although the exact mechanisms may vary with the main pathology. Iron treatment has been associated with acute exacerbations of infection, in particular malaria. In most instances parenteral iron was used. In the neonate parenteral iron is associated with serious E. coli sepsis. In one country, with endemic malaria, parenteral iron was associated with increased rates of malaria and increased morbidity due to respiratory disease in infants. In contrast in non-malarious countries studies of oral iron supplementation have if anything shown a reduction in infectious morbidity. Methodological problems in the latter reports indicate the need for further controlled prospective studies with accurate morbidity recording if informed recommendations are to be made.
One hundred and nine (9·8%) out of 1103 malaria patients examined in Sabah were deficient in glucose-6-phosphate dehydrogenase (G6PD). Sixty-nine of these G6PD-deficient patients were randomly allocated to one of three treatment regimes with (a) chloroquine, (b) chloroquine and primaquine or (c) sulfadoxine-pyrimethamine (Fansidar). No haemolysis was observed in group (a); except for a single mild case, no haemolysis was seen in group (c). However, in the primaquine group (23 patients), haemolysis occurred in seven of the 16 patients who had complete G6PD deficiency. Of these seven, five required blood transfusion and the other two developed acute renal failure, one requiring peritoneal dialysis. In the Fansidar group (c), four of the 22 patients took more than 15 days to clear the parasitaemia. Chloroquine resistance to falciparum infection was common in the patients given this anti-malarial.
Study site: Queen Elizabeth Hospital, Kola Kinabalu, Sabah, Malaysia
A total of 1008 healthy unrelated young adult male police and military recruits, 317 from Brunei, 398 from Sabah and 293 from Sarawak, were examined for G-6-PD deficiency. The frequency in the 317 Brunei recruits, who were all of Malay origin, was 6.3 %. In Sabah the frequencies for the four main ethnic groups were 12.1 % in 165 Kadazans, 4.1% in 73 Malays, 3.4 % in 68 Bajaus and 24.2 % in 33 Muruts. In Sarawak the frequency was 11.6 % in 95 recruits of Malay origin. Three among 56 Ibans and one among 80 Sea Dayaks were found to be enzyme-deficient, but the numbers examined of these groups were too small for estimation of the frequency. The overall frequency for the Malay group in Brunei, Sabah and Sarawak was 7.0% in 485 persons examined.
Massive pulmonary embolism (PE) is not an uncommon condition, and it usually carries a high risk of mortality. It is one of the fatal conditions that commonly affect young patients. A definitive treatment for patients with massive PE is still lacking, and surgical intervention carries a substantial mortality risk. Thus, percutaneous intervention (clot fragmentation and/or aspiration) remains an option in some patients, specifically in those with a risk of bleeding, contraindicating the use of thrombolysis. There have been no randomized trials to validate percutaneous intervention in massive PE. A sufficient level of evidence is still lacking, and its use depends upon the expert committee's opinion and study of previous case reports. We present a 23-year-old man with first onset massive PE secondary to protein C deficiency, who was treated successfully with the combination of systemic thrombolysis and percutaneous interventions.
Matched MeSH terms: Protein C Deficiency/complications*
IgA deficiency is the most common primary immunoglobulin deficiency. The prevalence in Caucasians is around one in 500, whereas in some Asian populations it is very uncommon. Most individuals with IgA deficiency are clinically asymptomatic. Those with symptoms of immunodeficiency have predominantly sinopulmonary or gastrointestinal infections, which are more severe when associated with IgG2, IgG4 or specific antibody deficiency. IgA deficiency is believed to be one end of a spectrum of immunodeficiency with common variable immunodeficiency at the most severe end. Although primary IgA deficiency is the most commonly encountered form, secondary deficiencies due to drugs or viral infections are recognized. IgA deficiencies can be partial or transient. Primary IgA deficiency is caused by a defect of terminal lymphocyte differentiation, which leads to underproduction of serum and mucosal IgA; affected individuals have normal IgA genes. A number of non-immunoglobulin genes have been implicated in IgA deficiency. There have been many diseases reported in association with IgA deficiency, particularly autoimmune diseases. The most common association is with coeliac disease (CD), which has special significance since CD is usually diagnosed by detection of specific IgA antibodies that are obviously lacking in IgA deficiency. There is no specific treatment for patients with symptomatic IgA deficiency. Antibiotics are prescribed in those with acute infections. A significant proportion of IgA-deficient individuals are reported to have anti-IgA antibodies in their serum. Although blood or blood products given to IgA-deficient individuals can lead to severe, even fatal, transfusion reactions, such reactions are rare.
Matched MeSH terms: IgA Deficiency/complications; IgA Deficiency/metabolism; IgA Deficiency/pathology*
Emerging epidemiological evidence suggests that patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may have a higher risk of developing diabetes. The aim of the review was to synthesise the evidence on the association between G6PD deficiency and diabetes. A systematic search on Medline, EMBASE, AMED and CENTRAL databases for studies published between January 1966 and September 2016 that assessed the association between G6PD deficiency and diabetes was conducted. This was supplemented by a review of the reference list of retrieved articles. We extracted data on study characteristics, outcomes and performed an assessment on the methodological quality of the studies. A random-effects model was used to compute the summary risk estimates. Fifteen relevant publications involving 949,260 participants were identified, from which seven studies contributed to the meta-analysis. G6PD deficiency was associated with a higher odd of diabetes (odds ratio 2.37, 95% confidence interval 1.50-3.73). The odds ratio of diabetes among men was higher (2.22, 1.31-3.75) compared to women (1.87, 1.12-3.12). This association was broadly consistent in the sensitivity analysis. Current evidence suggests that G6PD deficiency may be a risk factor for diabetes, with higher odds among men compared to women. Further research is needed to determine how G6PD deficiency moderates diabetes.
This study was aimed at determining the prevalence of anaemia amongst the Malaysian Cohort participants and the associated risk factors. This was a cross-sectional study that involved 102,388 participants from The Malaysian Cohort (TMC) aged between 35 and 70 years old recruited from April 2006 to September 2012. Venous blood was taken for the full blood count. The prevalence of anaemia was 13.8% with majority having the microcytic-hypochromic type (59.7%). Comparison between the ethnic groups showed that Indians have the highest prevalence of anaemia (19.9%), followed by Malays (13.1%), and Chinese (12.0%). The prevalence of anaemia was substantially higher in females (20.1%) compared to males (4.9%). Amongst the female participants, the prevalence of anaemia was highest amongst those who were younger than 49 years old and decreased as the age increased. In contrast, the prevalence of anaemia in males increased with age. Gender, ethnicity, age, marital status, presence of platelet disorders and kidney disease were significant risk factors associated with anaemia and contributed to 14.9% of the risk of developing anaemia in this population. The prevalence of anaemia amongst the Malaysian Cohort participants is 13.8% with the majority having the microcytic and hypochromic type implying iron deficiency as the main cause. It is important that those who have anaemia be further investigated and treated.
Study name: The Malaysian Cohort (TMC) project
The clinical severity of the mutations causing beta-thalassaemia in West Malaysia is presented. Thalassaemia clinical scores (Thal CS), a scoring system, has been formulated to predict clinical severity. It is the type of beta-thalassaemia mutation present that decides on the clinical phenotype. The most severe beta-thalassaemia mutation is assigned a score of 4. A score of 8 indicates a severe thalassaemia phenotype. Alpha-thalassaemia, increased synthesis of Hb F, and glucose-6-phosphate deficiency may ameliorate the clinical condition at phenotype level, and the co-inheritance of hereditary ovalocytosis aggravates it.
The National University of Singapore Heart Study measured cardiovascular risk factors, including selected plasma vitamins, on a random sample of the general population aged 30 to 69 years. Plasma vitamins A and E were normal and similar by ethnic group. Mean plasma vitamin A levels were: Chinese (males 0.68 and females 0.52 mg/L), Malays (males 0.67 and females 0.54 mg/L), and Indians (males 0.66 and females 0.51 mg/L). Mean plasma vitamin E levels were: Chinese (males 12.6 and females 12.6 mg/L), Malays (males 13.6 and females 13.3 mg/L), and Indians (males 12.9 and females 12.8 mg/L). No person had plasma vitamin A deficiency (< 0.01 mg/L) and only 0.1% had vitamin E deficiency (< 5.0 mg/L). In contrast, plasma vitamin C was on the low side and higher in Chinese than Malays and Indians. Mean plasma vitamin C levels were: Chinese (males 6.3 and females 8.4 mg/L), Malays (males 5.1 and females 6.4 mg/L), and Indians (males 5.7 and females 6.9 mg/L). Likewise, the proportions with plasma vitamin C deficiency (< 2.0 mg/L) were lower in Chinese (males 14.4 and females 0.7%), than Malays (males 19.7 and females 7.2%), and Indians (males 17.8 and females 11.0%). Relatively low levels of plasma vitamin C may contribute to the high rates of coronary heart disease and cancer in Singapore. In particular, lower plasma vitamin C in Malays and Indians than Chinese may contribute to their higher rates of coronary heart disease. However, plasma vitamin C does not seem to be involved in the higher rates of cancer in Chinese than Malays and Indians. The findings suggest a relatively low intake of fresh fruits and a higher intake is recommended. Also, food sources of vitamin C may be destroyed by the high cooking temperatures of local cuisines, especially the Malay and Indian ones.
Matched MeSH terms: Ascorbic Acid Deficiency/blood; Vitamin E Deficiency/blood
We report a full-term baby boy who presented soon after birth with severe congenital rickets. Maternal and neonatal vitamin D levels were very low and the infant responded well to oral vitamin D. Transient secondary hyperparathyroidism normalised on treatment. The mother's vitamin D deficiency was attributed to the region's cultural dress code which prevents exposure to sunlight. There has not been a previous report of severe congenital rickets from this region.
This is a retrospective study of the epidemiology, clinical features, laboratory findings, treatment and outcome of haemorrhagic disease in 42 Kelantanese infants who were admitted to Hospital Universiti Sains Malaysia during a 2-year period (1987-1988). Classical haemorrhagic disease of the newborn was the commonest presentation (48%), followed by early onset (29%) and late onset (24%) disease. Home deliveries accounted for 81% of the affected infants. Most of these babies were not given vitamin K at birth in contrast to those delivered in hospitals. All except one infant were breastfed. The six commonest presenting clinical features were pallor, jaundice, umbilical cord bleeding, tense fontanelle, convulsions and hepatomegaly. All the infants had prolonged prothrombin and partial thromboplastin times which were corrected by administration of vitamin K. Subdural haemorrhage was the commonest form of intracranial haemorrhage, followed by subarachnoid haemorrhage. The overall case fatality rate was 14%. The results of this study once again emphasize the value of vitamin K prophylaxis in the newborn.
Matched MeSH terms: Vitamin K Deficiency Bleeding/blood; Vitamin K Deficiency Bleeding/classification; Vitamin K Deficiency Bleeding/epidemiology*; Vitamin K Deficiency Bleeding/therapy*
The release of DNA into the cytoplasm upon damage to the nucleus or during viral infection triggers an interferon-mediated defense response, inflammation and cell death. In human cells cytoplasmic DNA is sensed by cyclic GMP-AMP Synthase (cGAS) and Absent In Melanoma 2 (AIM2). Here, we report the identification of a "natural knockout" model of cGAS. Comparative genomics of phylogenetically diverse mammalian species showed that cGAS and its interaction partner Stimulator of Interferon Genes (STING) have been inactivated by mutations in the Malayan pangolin whereas other mammals retained intact copies of these genes. The coding sequences of CGAS and STING1 are also disrupted by premature stop codons and frame-shift mutations in Chinese and tree pangolins, suggesting that expression of these genes was lost in a common ancestor of all pangolins that lived more than 20 million years ago. AIM2 is retained in a functional form in pangolins whereas it is inactivated by mutations in carnivorans, the phylogenetic sister group of pangolins. The deficiency of cGAS and STING points to the existence of alternative mechanisms of controlling cytoplasmic DNA-associated cell damage and viral infections in pangolins.
Manifestations of vitamin deficiencies observed in 6,000 Tamil and 4,000 Malay children and young adults during a survey carried out by the Institute for Medical Research in the Federated Malay States included phrynoderma, Bitot spots
and angular stomatitis. They were more frequent in Tamils than in Malays. Phrynoderma and Bitot spots responded rapidly to administration of vitamin A or carotene, though in some patients with phrynoderma improvement was not attained unless also the protein intake was increased and vitamin B complex added. Angular stomatitis was benefited by administration of riboflavin or vitamin B complex. The clinical and histologie observations of phrynoderma in Tamils and Malays in Malaya were identical with those previously reported in Chinese, Ceylonese and southern Indians. A supplementary food ration, composed of soy beans, skim milk powder, dal and red palm oil, given to Tamil children on rubber estates not only increased the general state of health but led to a rapid regression of the manifestations of vitamin deficiencies.