Comparison of classical and non-classical turner syndrome at NICH Karachi

Objective: to analyse chromosomal abnormalities of the patients who were referred for the screening of short stature and delayed puberty and to verify the association between karyotype and phenotype in confirmed Turner Syndrome [TS] patients

Study Design: descriptive study

Place and Duration of Study: department of Pediatric Endocrinology and Diabetes Unit-II, National Institute of Child Health, Karachi, from January 2011 to June 2016

Methodology: patients referred for the evaluation of short stature or delayed puberty were for the assessment of karyotype and phenotype correlations; standard karyotyping was executed and analysed on the basis of routine G-banding technique. Echocardiography and pelvic ultrasonography was also performed

Results: the study population consisted of 79 registered patients, with short stature and delayed puberty 48/79 [60.75%], short stature 68/79 [86.07%], and ambiguous genitalia 5/79 [6.32%]. Conferring to the karyotype analysis, classical Turner Syndrome 45, X was found in 42/79 [53.16%], isochromosomes 13/79 [16.45%], and mosaicism was present in 11/79 [14.1%]. Only 7/79 [8.86%] cases were diagnosed in infancy

Conclusion: the results of the study showed the consistency of short stature and delayed puberty in most of patients. Monosomy of X chromosome was the commonest followed by isochromosomes, mosaicism and structural abnormalities of X chromosome. No remarkable difference was found among classical and non-classical TS patients' height

Precocious puberty in children

To determine the etiology of precocious puberty in children and to compare the clinical and laboratory parameters of central and peripheral precocious puberty. Cross-sectional study. Endocrine Clinic at National Institute of Child Health, Karachi, from January 2009 to December 2011. Children presenting with precocious puberty were included. The age of onset of puberty was documented. Clinical evaluation, Tanner staging, height, height SDS, weight, weight SDS, body mass index, bone age, pelvic USG, plasma estradiol level and GnRH stimulation were done. Ultrasound of adrenal glands, serum level of 17 hydroxyprogesterone, ACTH, Renin, aldosterone and testosterone were performed in children with peripheral precocious puberty. MRI of adrenal glands and gonads was done in patients with suspected tumor of that organ and MRI of brain was done in patients with central precocious puberty. Skeletal survey was done in patients with Mc Cune-Albright syndrome. CAH [81.8%] indentified as a main cause in peripheral percocious puberty and idiopathic [67.74%] in central precocious puberty. Eighty five patients were registered during this period. The conditions causing precocious puberty were central precocious puberty [36.47%], peripheral precocious puberty [38.82%], premature pubarche [10.58%] and premature thelarche [14.11%]. There was a difference in the age of onset of puberty in case of central precocious puberty [mean=3, 2-6 years] versus peripheral precocious puberty [mean=5.25; 3.62 - 7.0 years]. Children with central precocious puberty showed higher height SDS, weight SDS, FSH, LH than those with peripheral precocious puberty. Etiology in majority of cases with peripheral precocious puberty was congenital adrenal hyperplasia and idiopathic in central precocious puberty. Central precocious puberty children showed higher height SDS, weight SDS, FSH, LH than peripheral precocious puberty

Effect of intravenous pamidronate treatment in children with osteogenesis imperfecta

To assess the beneficial effect of intravenous pamidronate treatment in children with osteogenesis imperfecta [OI]. Experimental study. Endocrine Unit at the National Institute of Child Health, Karachi, Pakistan, from January 2007 to December 2011. All children diagnosed with osteogenesis imperfecta on the basis of repeated spontaneous fractures and typical radiological findings registered during the study period, were included in this study. Pamidronate therapy were offered to those with more than 3 fractures per year or had platyspondyly. Pamidronate disodium was diluted in isotonic saline and administered by slow ravenous infusion over 3 hours in a dosage 1 mg/kg/day for 3 consecutive days 3 monthly for 2 years. Fracture rate, bone mineral density [BMD], mobility score, wellbeing and pain episodes were evaluated at baseline and 2 years after the treatment. Good response was defined as less than 2 fractures per year or mobility score improvement and poor response as more than 2 fracture per year with mobility score less than 2. Seventy two patients were included in this study. There were 40 boys and 32 girls with mean age of 3.64 +/- 3.2 years. The annual fracture rate decreased overall from 5.8 +/- 1.61 to 0.6 +/- 0.93 [p < 0.001]. BMD Z-score improved from -5.3 +/- 1.74 to -1.7 +/- 0.72 [p < 0.001]. Mobility score was 0.94 +/- 1.30 at baseline and 2.5 +/- 1.02 at the end of the treatment [p < 0.001]. Wellbeing gained from 3.63 +/- 1.44 to 7.8 +/- 1.18 [p < 0.001] and pain episode improved from 24.1 +/- 8.15 to 2.7 +/- 8.31 [p < 0.001]. Good response was noted in 92% of patients and poor response in 8% patients. Bisphosphonate seems to be an effective symptomatic treatment for children with osteogenesis imperfecta irrespective of severity of mutation or clinical phenotype. Cyclical bisphosphonate therapy has a positive effect on fracture rate, BMD, mobility score, wellbeing and pain episode

Celiac disease; effectiveness of treating previously untreated patients with both a gluten free diet and bisphosphonate, gluten free diet alone

To evaluate effectiveness of treating previously untreated patients with celiac disease with both a gluten free diet and bisphosphonate in order to significantly increase their BMD's to a greater extent than a gluten free diet alone. The study was conducted in National Institute of Child Health [NICH] Karachi to evaluate the effectiveness of treating previously untreated patients with celiac disease with a gluten free diet and bisphosphonate in terms of increase in bone mineral density in comparison to a gluten free diet alone over a period of three months [January 2013 - March 2013]. The study includes 30 children patients below fifteen years of age either sex. All study subjects were untreated celiac patients diagnosed by clinical presentation, small bowel histology and serologic testing. On day dexa scan was done. Fifteen patients kept on Gluten Free Diet [GFD] and remaining 15 patients kept GFD plus tablet of bisphosphonate. After three months dexa scan was repeated. The patients with other disease of bone or mineral metabolism, as well as subjects taking systemic glucocorticoids or high doses of thyroid hormones, were excluded. A total of 30 patients with celiac disease were included in this study. Out of 30 patients 18 [60%] were female and 12 [40%] male [M: F = 1:1.5]. Thirty patients were divided in two equal groups [15 patients in each group]. In group-I we gave gluten free diet and in group-II we gave gluten free diet and one tablet of bisphosphonate. Mean +/- SD of Bone Mineral Density [BMD] in group-I was 0.402 +/- 0.081 gm/cm2 [range=0.234 - 0.503 gm/cm2], and in group-II was 0.543 +/- 0.098 gm/cm2 [range= 0.402 - 0.743 gm/cm2], mean difference of bone mineral density was significant between two groups [P-value=0.0002]. At three months DEXA scan showed a significant rise in BMD in group-II as compared to group-I

Etiological diagnosis of undervirilized male / XY disorder of sex development

To do clinical, hormonal and chromosomal analysis in undervirilized male / XY disorder of sex development and to make presumptive etiological diagnosis according to the new Disorder of Sex Development [DSD] classification system. Case series. Endocrine Unit at National Institute of Child Health, Karachi, Pakistan, from January 2007 to December 2012. Patients of suspected XY DSD / undervirilized male visiting endocrine clinic were enrolled in the study. Criteria suggested XY DSD include overt genital ambiguity, apparent female/male genitalia with inguinal/labial mass, apparent male genitalia with unilateral or bilateral non-palpable testes, micropenis and isolated hypospadias or with undescended testis. The older children who had delayed puberty were also evaluated with respect to DSD. As a part of evaluation of XY DSD, abdominopelvic ultrasound, karyotype, hormone measurement [testosterone, FSH, LH], FISH analysis with SRY probing, genitogram, laparoscopy, gonadal biopsy and HCG stimulation test were performed. Frequencies and percentages applied on categorical data whereas mean, median, standard deviation were calculated for continuous data. A total of 187 patients met the criteria of XY DSD. Age ranged from 1 month to 15 years, 55 [29.4%] presented in infancy, 104 [55.6%] between 1 and 10 years and 28 [15%] older than 10 years. Twenty five [13.4%] were raised as female and 162 as [86.6%] male. The main complaints were ambiguous genitalia, unilateral cryptorchidism, bilateral cryptorchidism, micropenis, delayed puberty, hypospadias, female like genitalia with gonads, inguinal mass. The karyotype was 46 XY in 183 [97.9%], 46 XX in 2 [1.1%], 47 XXY in 1 [0.5%], 45 X/46 XY in 1 [0.5%] patient. HCG stimulation test showed low testosterone response in 43 [23%], high testosterone response in 62 [33.2%], partial testosterone response in 32 [17.1%] and normal testosterone response in 50 [26.7%]. Genitogram was carried out in 86 [45.98%] patients. Presumptive etiological diagnosis of androgen sensitivity syndrome/ 5-alpha reductase deficiency, testicular biosynthetic defect/ leydig cell hypoplasia, partial gonadal dysgenesis, ovotesticular DSD, XX testicular DSD, mixed gonadal dysgenesis, testicular vanishing syndrome, klinefelter syndrome, hypogonadotropic hypogonadism, isolated hypospadias and isolated micropenis was made. Clinical, chromosomal and hormonal assessment may help in making the presumptive etiological diagnosis. Further molecular genetics analysis are needed in differentiating these abnormalities and to make a final diagnosis

Hyperinsulinemia and waist circumference in childhood metabolic syndrome

To determine the characteristics of obese children presenting at a tertiary care hospital and the frequency of metabolic syndrome [MS] in them using two paediatric definitions. Cross-sectional study. The Endocrine Clinic of National Institute of Child Health, Karachi, from November 2005 till May 2008. A total of 262 obese children aged 4-16 years, with BMI greater than 95th percentile were included Children having obesity due to syndromes, medications causing weight gain, chronic illness and developmental disability were excluded. Blood pressure, waist circumference, fasting triglycerides, HDL, insulin and glucose levels were obtained. Obesity was defined as BMI > 95th percentile for age and gender according to the UK growth reference charts. The prevalence of metabolic syndrome was estimated using to the De Ferrantis and Lambert definitions. The frequency of MS varied between 16% and 52% depending on whether insulin levels were included in the definition. There was a significant positive correlation[r] when the metabolic parameters were correlated with waist circumference and insulin levels, except HDL which was negatively correlated. All the metabolic parameters like waist circumference, triglycerides, high density lipoprotein cholesterol and systolic blood pressure increased considerably circumference, triglycerides, high density lipoprotein cholesterol and systolic blood pressure increased considerably across the insulin quartile [p< 0.05]. The most noteworthy anthropometric and metabolic abnormality were the waist circumference [46.5%] and insulin levels [58%] respectively. There was a marked difference in the frequency of metabolic syndrome according to the definition used. The waist circumference and hyperinsulinemia are significant correlates of MS in obese children. There is a need for establishing normal insulin ranges according to age, gender and pubertal status. The clinical examination and investigations ought to include waist circumference and insulin levels together as a part of the definition of MS, for early detection and intervention of childhood obesity

Effects of diabetes self-management education on glycaemic control in children with insulin-dependent diabetes mellitus

To evaluate the effect of diabetes self-management education [DSME] on glycaemic control [HbA1c] in Pakistani children suffering from type-1 diabetes mellitus. Quasi-experimental study. This study was conducted at the Diabetic OPD of National Institute of Child Health, Karachi, from April to September 2009. Sixty children with a mean age of 9.94 years with type-1 Diabetes mellitus [T1DM] were selected conveniently from the diabetic OPD. The patients along with their parents/caregivers attended a modular series of diabetes self-management education program consisting of 2 sessions. Customized program was designed to educate children regarding general information about the disease, basic insulin therapy, planning for hypoglycaemia, hyperglycaemia, activity, traveling and basic nutritional management. It was conducted by a multidisciplinary paediatric diabetes team including an endocrinologist, general paediatrician, nutritionist and diabetic nurse. The educational sessions were followed by monthly revision exercises. HbA1c levels were measured at baseline and after 3 months and compared using paired sample t-test. Out of a total of 60 patients, 50 completed the trial. There was a significant decrease in the HbA1c levels after the DSME program. The mean pre- and postintervention HbA1c levels were 9.67 +/- 0.65 and 8.49 +/- 0.53 respectively with a p-value < 0.001. In the studied group, DSME programs helped to improve glycaemic control. It should be an integral part of patient treatment in diabetic care setups

Investment in paediatric tuberculosis prevention in Pakistan: loss or gain?

To assess the effectiveness of paediatric tuberculosis prevention, by reevaluation factors in children exposed to tuberculosis from less privileged strata of Pakistan. This cross sectional descriptive study was conducted at National Institute of Child Health, from January 2004 to December 2005. Paediatric patients under 15 years of either gender, diagnosed with active tuberculosis were enrolled. Interviews were conducted with parents regarding common preventive measures and factors advocating tuberculosis spread. Later factors leading to non-compliance to safety recommendations were also evaluated. Fifty five [70%] children younger than 5 years, had index cases in direct contact within their own house. Fifteen [14%] patients contracted the infection from neighbours, with 11 being older than 5 years. There were 82 [51%] cases with Protein Calorie Malnutrition [PCM]. Total of 66 [41%] cases of PCM were <5 years age [p <0.005]. Data showed 123 [77%] children living in a family with 5 or more members. Sixty eight [55%] children of these large families had to live in a single room house. There is a high frequency of direct contact tuberculosis in children belonging to the lower socio-economic class. This is attributed to poor housing condition and over crowding. The current paediatric tuberculosis prevention strategies as adapted from World Health Organizations' Millennium Development Goals are ineffectual to make changes in children exposed to tuberculosis from less privileged strata of Pakistan. Our societal and demographic factors remain static, continually exposing our children to higher risk of tuberculosis exposure

Acquired aplastic anemia: treatment in a developing country

The aim of this study was to evaluate the clinical presentation of aplastic anemia as well as to assess the efficacy of Cyclosporin-A in patients with aplastic anemia. This is a hospital based interventional study. During the three year study period, 44 children were enrolled. Mean age was 9.3 years and there was a male predominance. Most common clinical presentation was anemia and bleeding. Four children died before therapy was started. Cyclosporin-A was started in 40 patients. Eleven patients died before completion of therapy and three patients were lost to follow-up. Out of 26 patients who completed therapy, 11 were cured and 9 were responders while 6 were non responders according to the selected criteria. In developing third world countries like Pakistan majority of the patients with aplastic anemia cannot afford BMT. Alternative modalities of treatment must therefore be looked into. Cyclosporin-A seems to be a reasonable therapeutic option in such cases

Management of Acute Asthma in children using metered dose inhaler and small volume nebulizer

To determine whether the administration of 32 - agonist by Metered Dose inhaler [MDI] with accessory device [AD] is a as effective as the administration of 32 - agonist by small volume nebulizers [SVN] for the treatment of acute asthma. A cross sectional study was conducted at Emergency Room [ER] of National Institute of Child Health [NICH], Karachi, between October 2000 to March 2001. This study included 150 children, 6 months and older with a history of wheeze and presenting with an acute asthma exacerbation. Children were categorized into mild, moderate and severe asthma according to medical scoring system. Children were assigned randomly into group A and B to receive standard dose of 32 - agonist [salbutamol] by MDI/AD [group A] or SVN [group B]. Baseline : characteristics and asthma severity were recorded. All variables [dyspnoea, use of accessory muscles, cyanosis, respiratory rate, heart rate, blood pressure, oxygen saturation, pulsus paradoxus, and wheeze] and Peak Expiratory Flow Rate [PEFR] in children 5 years and older, were determined at pre and post inhalation therapy. Both groups did not differ in demographic characteristics. There were no significant differences in outcome measures. In children treated with MDI/ADs and SVNs. PEFR increased significantly in both the groups after completion of treatment, but PEFR was not statistically significant when compared in between groups. The data suggested that MDI/AD is an effective alternative to nebulizer for the treatment of children with acute asthma exacerbation in the ER

Analysis of clinical profile of children with congenital adrenal hyperplasia

To evaluate our data of children with congenital adrenal hyperplasia [CAH]. Descriptive study. The study was conducted at the National Institute of Child Health, from 2001-2004. All children with CAH presenting at the endocrine clinic were included. A questionnaire was completed regarding age, sex, mode of presentation etc. Out of 54 patients of CAH seen at our clinic in five years, we found significantly fewer males [9 - 16.6%] than females [45 -83.4%]. Nineteen had salt wasting [SW] and 35 had simple virilizing [SV] type of CAH. Time elapsed before the diagnosis was 46 days in our children with SW variety. The fewer number of salt waster CAH along with the fewer male patients strongly indicate that these children may be dying from an undetected salt wasting episode or we may have a different genotype. It is therefore recommended that increased awareness of the condition is required both in the general population as well as the medical community. Further work on the genotype/phenotype correlation is also needed to look at the local genotype involved in this condition