Molecular detection of genetic defects in ambiguous genitalia (AG) and congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) is a group of inherited disorders affecting the enzymes catalyzing the synthesis of steroids in the adrenal cortex.Malfunction of 21-hydroxylase is the most frequent defect among these disorders.This enzyme is essential for the synthesis of cortisol and aldosterone.The decreased level of serum cortisol in patients with 21-hydroxylase cleticiency stimulates ACTH secretion, which result in elevated levels of steroid precursors as 17-hydroxyprogesterone and increased production of adrenal androgens causing virilization.Deficiency of the 2 I -hydroxylase (21-0H) enzyme is by far the most common form of CA H which arises as a result of deletions or deleterious mutations in the active gene (CYP21) located on chromosome 6p21.3.Many different mutations of the CY P21 gene cause varying degrees or impairment of 21-0H activity that results in a spectrum of disease statement.There is no sharp limit between the salt-wasting, the simple virilizing and the late onset forms.The objective of our study was to determine the 21-0H deticiency mutation defects and correlate the genotype with their phenotypic statement of the disease.vVe performed mutational analysis using Polymerase Chain Reaction-Allele Specific Oligonucleotide Hybridization (PCR-ASOH) technique on patients who were suspected to have CAH as they presented with ambiguous genitalia (AG) and or electrolyte derangement.Among the 52 patients, 3 had Val281 Leu mutation (5.76%). 2 had Pro30Leu mutation (3.85%). I had Gln318stnp mutation (1.92%) and in 46 (88.l6%) patients mutation was detected.The three patients with Val281 Leu mutation had presented with adrenal crises during in infancy and was classified as salt losers and treated with glucocorticoids and mineralocorticoids.These 3 patients could well be the other 40% who are categorized as salt-losers. The two patients with Pro30Leu mutations have normal male external genitalia and presented with hyponatraemia and hyperkalaemia.Only one patients required mineralocorticoid therapy that was given for about 5 months duration.Subsequently he hold normal electrolytes level even without mineralacorticiod therapy. The Gln3I8stop mutation was identitied in one patient who presented with ambiguous and adrenal crises.Our study showed that the cases with genotype Val281 Leu, Pro30Leu and Gln318stop mutations correlated with their phenotype. The mutation analysis of CYP21 gene proved to be a good complementary investigation and supportive to the diagnosis and management of our CAH patients

Clinical presentation of congenital adrenal hyperplasia in selected multiethnic paediatric population

A clinical descriptive study was done to determine the sociodemographic, laboratory and clinical characteristics of patients with congenital adrenal hyperplasia (CAH) referred to Hospital Putrajaya, a tertiary endocrine centre in Malaysia. Electronic laboratory data of 51 CAH patients were obtained. The demographics and clinical details of the study population were acquired from a questionnaire completed by parents of participants. There were 25 males (49%) and 26 females (51%), of which, 58.8% were Malays. Median age of participants was 4 years whilst median age at diagnosis of CAH was two years. Parental consanguinity was documented in three patients (5.9%). Patients originated from Johor (19.6%), Selangor (19.6%), Negeri Sembilan (17.6%) and Kedah (13.7%). Majority of patients were diagnosed after one week of life (80.4%) although more females were diagnosed under the age of one week compared to males (p=0.041). Most females presented with ambiguous genitalia (42.3%) [p=0.001] whereas 72% of males presented with salt wasting (p=0.003). No significant associations between race and all other variables, though interestingly three Malay patients presented with ambiguous genitalia and hypertension. Equal gender distribution noted as expected in an autosomal recessive condition, although not in keeping with other Asian countries. Early diagnosis in females attributed to obvious genital ambiguity at birth. Varied clinical presentation, although in minority, necessitates genetic studies for prompt diagnosis and treatment. Considering that majority of patients presented with salt wasting and the age at diagnosis was delayed, the introduction of a neonatal screening programme is essential in Malaysia

Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus

OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. RESEARCH DESIGN AND METHODS: This case–control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS) in OGTT and surrogate index of SI from the minimal model (calculated SI, CSI). Acute insulin response (AIR) was obtained from IVGTT. Total BC was computed as incremental area under the curve of insulin/incremental area under the curve of glucose, during OGTT (BC(OG)) and IVGTT (BC(IV)), respectively. Disposition index (DI) was calculated using the product of insulin sensitivity and insulin secretion. GLP-1 response to oral glucose was calculated as incremental area under the curve of GLP-1 (ΔAUC(GLP-1)). Per cent incretin effect was estimated as 100×(BC(OG)−BC(IV))/BC(OG)). RESULTS: The YT2DM had marked impairment in BC (>80% reduction in AIR and BC(OG), p<0.001) and lower QUICKI (p<0.001), OGIS (p<0.001) and CSI (p=0.015) compared with controls. There was no difference in GLP-1 at all time points and ΔAUC(GLP-1) but the per cent incretin effect was reduced in the YT2DM compared with controls (12.1±8.93 vs 70.0±4.03, p<0.001). CONCLUSIONS: Asian YT2DM showed similar GLP-1 response to oral glucose as controls but reduced incretin effect, BC and insulin sensitivity. The lack of compensatory mechanisms, as shown by the DI may be partly ascribed to the impaired incretin effect, similar to that of adult T2DM. TRIAL REGISTRATION NUMBER: NMRR-12-1042-13254

Diabetic ketoacidosis at diagnosis of type 1 diabetes mellitus in Malaysian children and adolescents

Type 1 diabetes mellitus (DM) accounts for more than 90% of childhood and adolescent diabetes. Of the estimated 479,600 type 1 diabetic children worldwide, 24% were from the South-East Asian region and 6.4% from the Western Pacific region.2–3 The annual incidence for childhood type 1 DM (0–14 year age group) ranged from 0.1 per 100,000 in China to 57.6 per 100,000 in Finland.3–5 The incidence of type 1 DM appeared to be low in the Western Pacific region with the exception of Australia and New Zealand. In Malaysia, type 1 DM was estimated to account for 69.2% of children and adolescents with diabetes

Periodontal health status of Malaysian diabetic children and adolescent: a hospital based case-control study in Kuala Lumpur and Kuantan

Background: Diabetes mellitus (DM) is the major risk factor for periodontal disease (PD). PD includes a spectrum of disorders ranging from gingivitis to periodontitis. If undetected and left untreated the disease can lead to early tooth loss. Assessing PD health is beneficial for keeping good oral health, which affects on glycemic control of the children and adolescent with DM. Objectives: To evaluate the periodontal health status of Malaysian diabetic children and adolescents compared to healthy controls. Methods: Periodontal health related parameters were clinically assessed in 32 children and adolescents (10-19 years of age) with diabetes and 32 non-diabetic control subjects. Age, gender, Body Mass Index (BMI), CDC percentiles and smoking status matching were done and purposive sampling was applied. HbA1C (%) results within 3-6 months before oral health assessment was used to define glycemic control status of the subjects. A cross analysis and Independent sample-t test were applied to infer periodontal health status difference between cases and controls. Results: Most of the cases were Type-1 DM (68.8%) and diagnosed less than five years (68.2%). The cases had manifested an increased gingival inflammation and calculus significantly compared to controls. Regarding PD health assessment; clinical attachment loss (CAL), gingival index (GI), Modified Turesky Quigley Hein plaque index (TQHI) and bleeding on probing (BOP) were not significantly different except for Probing pocket depth (PPD); mean of (SE) (1.81±0.13) compared to controls (1.65 ±0.06). Higher mean of (SE) GI (0.9±0.82) were also noticed among cases than those of (0.8±0.11) controls. Conclusion: Periodontal screening & prevention programs at early age for DM children and adolescent should be considered for both oral health and glycemic controls. A further study with controlling; Insulin treatment, types of DM, DM duration, and oral hygiene practice and dietary habits should be conducted for more valid results

Periodontal disease in children and adolescent with diabetes mellitus

Background: Diabetes mellitus (DM) is the major risk factor for periodontal disease (PD). PD includes a spectrum of disorders ranging from gingivitis to periodontitis. If undetected and left untreated the disease can lead to early tooth loss. Assessing PD health is beneficial for keeping good oral health, which affects on glycemic control of the children and adolescent with DM. Objectives: To evaluate the periodontal health status of Malaysian diabetic children and adolescents compared to healthy controls. Methods: Periodontal health related parameters were clinically assessed in 32 children and adolescents (10-19 years of age) with diabetes and 32 non-diabetic control subjects. Age, gender, Body Mass Index (BMI), CDC percentiles and smoking status matching were done and purposive sampling was applied. HbA1C (%) results within 3-6 months before oral health assessment was used to define glycemic control status of the subjects. A cross analysis and Independent sample-t test were applied to infer periodontal health status difference between cases and controls. Results: Most of the cases were Type-1 DM (68.8%) and diagnosed less than five years (68.2%). The cases had manifested an increased gingival inflammation and calculus significantly compared to controls. Regarding PD health assessment; clinical attachment loss (CAL), gingival index (GI), Modified Turesky Quigley Hein plaque index (TQHI) and bleeding on probing (BOP) were not significantly different between cases and controls except for probing pocket depth (PPD); mean of (SE) (1.81±0.13) compared to controls (1.65 ±0.06). Higher mean of (SE) GI (0.9±0.82) were also noticed among cases than those of (0.8±0.11) controls. Conclusion: Periodontal screening & prevention programs at early age for DM children and adolescent should be considered for both oral health and glycemic controls. A further study with controlling; Insulin treatment, types of DM, DM duration, and oral hygiene practice and dietary habits should be conducted for more valid results. Key words: Periodontitis, Periodontal disease, Diabetes mellitus, Children, adolescen

Periodontal diseases in children and adolescent with diabetes mellitus

The periodontal health status of diabetic children and adolescent was evaluated in this case-control study. 64 subjects were included. Mean age (SD) of the cases and controls were 13.72(2.8) and 13.53(2.5) years. Four periodontal parameters were assessed. HbA1c (%) level within 3 to 6 months prior to check-up was used to defined subjects glycaemic control status. Analysis was done using IBM-SPSS 21. 96.8% of cases have periodontal disease. Probing pocket depth showed significantly deeper mean compared to controls. Higher mean of gingival index were also noticed among the cases. Periodontal screening could be recommended for DM children and adolescent in prevention of severe periodontal diseas