Identification of Variants and Mutational Analyses of Cardiac Myosin-binding Protein C (MYBPC3) Gene of Adult Bangladeshi Patients with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetic hereditary cardiomyopathy characterized by sudden cardiac death. Mutations in the MYBPC3 gene are often the most prevalent genetic abnormality in HCM with a prevalence ranging from 20.0 to 42.0%. The mutation spectrum is available for different countries, but such studies are lacking in the Asian population including Bangladeshi patients. A cross-sectional descriptive study was conducted for mutation analysis of the whole MYBPC3 gene on a cohort of 75 HCM Bengali Bangladeshi probands through Next Generation Sequencing at the Genetic Research Lab of Bangabandhu Sheikh Mujib Medical University from 2016 to 2019. The structural and functional impact of the mutations was further analyzed by in silico process. We analyzed the data and found 103 variants in 102 locations in the MYBPC3 gene. Variants were identified in both the coding region and the non-coding region. We found one possibly novel variant in the MYBPC3 gene. The findings of this research will help to develop a genetic database of HCM which will help in the early diagnosis and proper management of HCM patients in Bangladesh. One pathogenic splice donor variant (47356592 C >T) was found in the intronic region. Among the variants in the coding region, one missense mutation was pathogenic (NP₋000247.2: p.Asp770Asn) which was found in seven patients and another one is of conflicting interpretations of pathogenicity (NP₋000247.2: p.Ser217Gly) which was found in two patients. We have identified one in-frame deletion (NP₋000247.2: p.Ala433del) that is possible a novel variant responsible for the development of HCM.

Clinical Presentations of Acquired Hypothyroidism in Children: Experience in a Tertiary Care Hospital in Bangladesh.

A cross sectional study was conducted in Paediatric Endocrine Outpatient Department of BIRDEM General Hospital, a tertiary care centre in Dhaka, Bangladesh among patients diagnosed with acquired hypothyroidism during the period of January 2012 to December 2016. The study was done to find out the clinical presentations and associated disorders of all patients diagnosed with acquired hypothyroidism during the study period. Data were obtained by reviewing the medical records of the patients. Total 277 children were diagnosed of having thyroid disorders. Among them 145(52.3%) had acquired hypothyroidism. The commonest clinical presentations of children with acquired hypothyroidism were short stature (35.0%), excessive weight gain (31.5%), goiter (23.1%) and poor school performance (14.0%). Autoimmune hypothyroidism was found in 34.4% of children, sub-clinical hypothyroidism in 27.5% children and positive family history was found in 15.2% children with acquired hypothyroidism. The common associated diseases were diabetes and impaired glucose tolerance (4.9%), Down syndrome (3.5%), congenital heart disease (2.1%) and primary adrenal insufficiency (1.4%).

Clinical Presentation of Congenital Adrenal Hyperplasia in Children: Experience in a Tertiary Care Hospital of Bangladesh.

This cross sectional study was conducted in Paediatric Endocrine Outpatient Department of BIRDEM General Hospital, a tertiary care centre in Dhaka, Bangladesh among patients diagnosed with congenital adrenal hyperplasia (CAH) from January 2005 to December 2018. The study was aimed to find out the clinical and laboratory profile of all patients at presentation diagnosed with CAH during the study period. Data were obtained by reviewing the medical records of the patients. Total 102 children with CAH were diagnosed during the study period. Among them 68 were female and 34 were male (female to male ratio of 2:1). Median age was 3.5 month (range 0.2-158 month) and 5.5 month (range 1-108 month) in female and male respectively (p=0.42). Family history was available in 93 patients. Consanguinity was present in 16(17.2%), history of sib death in 12(12.9%), other family members were affected in 8(8.6%). Sixty patient (58.8%) had salt-wasting (SW), 39(38.2%) had simple virilizing (SV) and 3(2.9%) had non- classic form of CAH. Median age of presentation was 2 month (range 0.2-70 month) and 42 month (range 0.8-158 month) in SW and SV group respectively (p=0.001) and 119 month (range 108-152 month) in non- classic group. Common presentations were: genital ambiguity (64.7%), vomiting (46.5%), failure to thrive (41.6%), features of early puberty (precocious pseudopuberty) (24.5%), diarrhea (12.0%). Hyperpigmentation was noted in 49.0% of patients. Among the salt-wasting type in male failure to thrive (FTT) was the most common presentation (83.3%), followed by vomiting (75.0%). In female genital ambiguity was the commonest presentation (97.2%), followed by vomiting (77.1%). Among the simple virilizing type in male early puberty was the commonest presentation (100%) and genital ambiguity was the presenting feature in all the female (100.0%).

Prevalence of impaired glucose tolerance among children and adolescents with obesity.

The study was undertaken to see the prevalence of impaired glucose tolerance among children and adolescents with obesity, attending the Paediatric Endocrine OPD, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic disorders (BIRDEM), Dhaka, Bangladesh. A cross sectional study from January 2006 to December 2008 was conducted among obese children and adolescents (6-18 years). Children with any other endocrine disorder, dysmorphism/syndrome were excluded. Obesity was defined as BMI ≥ 95th percentile for age and sex using CDC growth chart. Children underwent two hours oral glucose tolerance test with 1.75 gm/kg or 75 gm of glucose, anthropometric and blood pressure measurement. Fasting serum insulin and lipid profile were measured. Impaired glucose tolerance (IGT) was defined as fasting plasma glucose (FPG) <7 mmol/L and 2 hours post glucose load ≥ 7.8 mmol/L to <11.1 mmol/L. Diabetes mellitus (DM) was defined as FPG ≥ 7 mmol/L or 2 hours post glucose load ≥ 11.1 mmol/L. Homeostasis model assessment was used to estimate insulin resistance. A total of 161 children presented with obesity. Male to female ratio was 1.3:1. Mean age was 10.3 ± 2 .5 years. Mean BMI was 27.86 ± 4.1 kg/m². IGT was found in 16.9% of children and adolescents. In children aged 6-10 years IGT was detected in 16.1% and in adolescents aged 11-18 years IGT was detected in 20%. Diabetes mellitus was detected in 2.1% of subjects, all were adolescents. Serum fasting insulin and hip circumference were significantly higher among children and adolescents with IGT compared to that of normal glucose tolerance. The high rate of IGT among obese children and adolescents is of concern. Factors contributing towards obesity needs to be identified and strategies should be planned for prevention and management of this health problem.