exudates and Congenital-Hypothyroidism

Topics: Adolescent; Adult; Afghanistan; Aged; Animals; Asia, Southeastern; Child; Child, Preschool; Congenital Hypothyroidism; Deficiency Diseases; Diet; Electrophoresis, Polyacrylamide Gel; Female; Goats; Goiter, Endemic; Humans; India; Infant; Infant, Newborn; Iodine; Malaysia; Male; Middle Aged; Myanmar; Pregnancy; Seasons; Sex Factors; Sri Lanka; Thailand; Thyroid Gland

Clinical diagnosis of congenital hypothyroidism (CH) is difficult at birth without neonatal screening. In line with the priorities of the national health services in Malaysia towards preventive medicine, early diagnosis and treatment of CH is emphasised. We conducted a pilot study at Kuala Lumpur's Maternity Hospital between April 1995 and November 1995 to estimate the incidence of CH and also evaluated the problems associated with large-scale neonatal screening using a commercial TSH kit on cord bloodspots.. A total of 11,000 newborns were screened using cord blood spots taken at birth.. Two hundred and fifty newborns (2.27%) hand cord TSH > 20 mlU/L and had to be recalled for re-evaluation. Of these, 4 had cord TSH of > 100 mlU/L; three were confirmed to have congenital hypothyroidism and one had transient hyperthyrotropinaemia. Our study estimated the incidence of CH to be one in 3,666 live births in Kuala Lumpur, Malaysia. Clinical features of hypothyroidism are subtle during the early weeks of life. However, prolonged neonatal jaundice (3/3), widely opened posterior fontanelle (3/3) and dry skin (3/3) were the common features in all our cases by 2-6 weeks of life.. This study suffered a high dropout rate. Twenty-six percent of the patients were not traceable after discharge and 48% did not respond to our recall. We stress the importance of public education and awareness in contributing to the cost-effectiveness of the screening program.

Topics: Congenital Hypothyroidism; Female; Fetal Blood; Humans; Hypothyroidism; Incidence; Infant, Newborn; Malaysia; Male; Neonatal Screening; Pilot Projects; Reagent Kits, Diagnostic; Thyrotropin

The c.2268dup mutation in the thyroid peroxidase (TPO) gene is the most common TPO alteration reported in Taiwanese patients with thyroid dyshormonogenesis. The ancestors of these patients are believed to originate from the southern province of China. Our previous study showed that this mutation leads to reduced abundance of the TPO protein and loss of TPO enzyme activity in a Malaysian-Chinese family with goitrous hypothyroidism. The aim of our study was to provide further data on the incidence of the c.2268dup mutation in a cohort of Malaysian-Chinese and its possible phenotypic effects.. Cohort study.. Twelve biologically unrelated Malaysian-Chinese patients with congenital hypothyroidism were recruited in this study. All patients showed high thyrotropin and low free thyroxine levels at the time of diagnosis with proven presence of a thyroid gland.. Screening of the c.2268dup mutation in the TPO gene in all patients was carried out using a PCR-direct DNA sequencing method.. Further screening for mutations in other exonic regions of the TPO gene was carried out if the patient was a carrier of the c.2268dup mutation.. The c.2268dup mutation was detected in 4 of the 12 patients. Apart from the c.2268dup and a previously documented mutation (c.2647C>T), two novel TPO alterations, c.670_672del and c.1186C>T, were also detected in our patients. In silico analyses predicted that the novel alterations affect the structure/function of the TPO protein.. The c.2268dup mutation was detected in approximately one-third of the Malaysian-Chinese patients with thyroid dyshormonogenesis. The detection of the novel c.670_672del and c.1186C>T alterations expand the mutation spectrum of TPO associated with thyroid dyshormonogenesis.

Topics: Asian People; China; Cohort Studies; Congenital Hypothyroidism; Exons; Female; Genetic Predisposition to Disease; Goiter; Humans; Infant; Infant, Newborn; Iodide Peroxidase; Malaysia; Male; Mutation; Prevalence; Sequence Analysis, DNA

The c.2268dup mutation in thyroid peroxidase (TPO) gene was reported to be a founder mutation in Taiwanese patients with dyshormonogenetic congenital hypothyroidism (CH). The functional impact of the mutation is not well documented. In this study, homozygous c.2268dup mutation was detected in two Malaysian-Chinese sisters with goitrous CH. Normal and alternatively spliced TPO mRNA transcripts were present in thyroid tissues of the two sisters. The abnormal transcript contained 34 nucleotides originating from intron 12. The c.2268dup is predicted to generate a premature termination codon (PTC) at position 757 (p.Glu757X). Instead of restoring the normal reading frame, the alternatively spliced transcript has led to another stop codon at position 740 (p.Asp739ValfsX740). The two PTCs are located at 116 and 201 nucleotides upstream of the exons 13/14 junction fulfilling the requirement for a nonsense-mediated mRNA decay (NMD). Quantitative RT-PCR revealed an abundance of unidentified transcripts believed to be associated with the NMD. TPO enzyme activity was not detected in both patients, even though a faint TPO band of about 80 kD was present. In conclusion, the c.2268dup mutation leads to the formation of normal and alternatively spliced TPO mRNA transcripts with a consequential loss of TPO enzymatic activity in Malaysian-Chinese patients with goitrous CH.

Topics: China; Congenital Hypothyroidism; Female; Genetic Markers; Genetic Predisposition to Disease; Goiter; Humans; Infant, Newborn; Iodide Peroxidase; Malaysia; Mutation; Polymorphism, Single Nucleotide

This study was designed to evaluate the karyotype pattern, clinical features and other systemic anomalies of patients with Down syndrome in Malaysia.. Retrospective analysis was performed on the case records of 149 patients confirmed as Down syndrome by cytogenetic analysis at Human Genome Centre and Genetic Clinic at the Universiti Sains Malaysia.. Among the 149 cases of Down syndrome presenting over a period of 4.2 years, free trisomy (non-disjunction) was present in 141 cases (94.6 percent). One case (0.7 percent) had translocation, and seven cases (4.7 percent) were mosaics. Average age at presentation was 10.6 months. Average maternal age at birth of the affected child was 32.3 years. The prominent craniofacial features noted were upslanting palpebral fissures (89.3 percent), flat facial profile (64.9 percent), low set ears (56.1 percent), epicanthic folds (17.5 percent) and protruding tongue (19.2 percent). A total of 52.6 percent of the cases had documented hypotonia. Characteristic limb and dermatoglyphic anomalies included short stubby fingers (24.5 percent), sandal gap (33.3 percent), unilateral or bilateral simian crease (36.8 percent) and clinodactyly (19.2 percent). Ophthalmological abnormalities, such as hypertelorism, were presented in 33.3 percent of the cases. Congenital heart disease was diagnosed in 35 out of 71 cases (49.3 percent) and gastrointestinal anomalies were noted in 18 out of 79 cases (22.7 percent) analysed.. Efforts to establish early diagnosis and a proper screening for high association with systemic anomalies should be undertaken among the Down syndrome patients in this population.

Topics: Adult; Cohort Studies; Congenital Hypothyroidism; Craniofacial Abnormalities; Down Syndrome; Female; Gastrointestinal Tract; Heart Defects, Congenital; Humans; Infant; Karyotyping; Limb Deformities, Congenital; Malaysia; Male; Maternal Age; Pregnancy; Retrospective Studies

A comparative epidemiological and anthropometric survey was conducted among Ibans, the largest indigenous ethnic group in Sarawak, in three regions where the endemicity of goitre exhibited marked differences , to assess the effect of endemic goitre on somatic growth. In the Ai river region the prevalence of goitre was 99.5%; 35% having grade 3 goitres, 55% grade 2 goitres and 9.5% grade 1 goitres. At Rubu the prevalence of endemic goitre was 74%; 3% having grade 3 goitre, 16% grade 2 goitre and 55% grade 1 goitre. In the Bajong region relatively few people were detected with goitre and most of these had migrated from other regions. Neurological cretinism was estimated at 3.6% in the severely goitrous Ai river population but was not detected in the other regions. Anthropometric data obtained from the three adult populations did not reveal any statistically significant differences in the following parameters: weight, height, weight/height ratio, height/sitting height ratios, head circumference, scapular skinfold thickness and left mid arm muscle circumference. The haemoglobin, serum total protein and serum albumin concentrations were similar in the three populations. It is concluded that endemic goitre occurs with a frequency of close to 100% in certain Iban populations which represents one of the highest incidences of endemic goitre in the world. Neurological cretinism is common in this population. Our observations suggest that body proportions and somatic growth do not vary among similar ethnic populations exhibiting greatly different endemicity of goitre. Although no iodine balance studies were performed, assessment of diets suggested that iodine deficiency is a significant contributory factor in the development of endemic goitre in Sarawak. Urgent attention to iodine supplementation is indicated to prevent the development of endemic goitre and neurological cretinism.

Topics: Adult; Congenital Hypothyroidism; Female; Goiter, Endemic; Growth; Humans; Malaysia; Male