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Progressive pseudorheumatoid dysplasia or spondyloepiphyseal dysplasia tarda is caused by a mutation in Wnt1 inducible signalling pathway protein 3 (WISP3) and passes in an autosomal recessive manner. Prevalence underestimated as one per million and most of the cases remain undiagnosed or treated as Juvenile Idiopathic Arthritis (JIA). Differentiation between JIA and PPRD is really challenging however, this case is genetically confirmed from our country. 7-year-old, short stature boy, with multiple joint swellings of hands and feet, initially suspected to have JIA and had been worked up and took treatment for that for the past 2 years. He had progressive stiffness of small joints. Baseline biochemistry, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor and ANA, were within normal limits. He was moderately growth hormone deficient. Thyroid function tests and insulin-like growth factor 1 (IGF-1) were within reference ranges. Skeletal survey showed typical findings of pseudorheumatoid skeletal dysplasia. Physical therapy and genetic counselling were done.

Background: Mucormycosis is a cause of fulminant necrotizing fungal infection in children with underlying immunocompromising condition. Rhino-orbito-cerebral infection is the most common form of mucormycosis in children with uncontrolled diabetes mellitus or diabetic ketoacidosis. Once considered a rare entity is now increasingly being reported especially in the diabetic population. The initial presentation can mimic a bacterial infection, thus a high index of suspicion is needed for timely intervention to reduce morbidity and mortality.Case report: We present a case of rhino-orbito-cerebral mucormycosis in two patients with diabetic ketoacidosis for the first time from Pakistan. Both the patients couldn’t survive due to late and extensive disease on presentation. Keywords: mucormycosis; rhino-orbito-cerebral mucormycosis; diabetic ketoacidosis; diabetes mellitus, pediatric; children

Introduction: Diabetes is associated with a high risk of cardiovascular disease (CVD). Hypertriglyceridemia & low HDL-C values are the most common symptoms of diabetic dyslipidemia. Elevated LDL-C is a well-known CVD risk factor. Objective: To determine the association of dyslipidemia and type 1 diabetes mellitus among children up to 16 years of age. Material & Method Study design: Case-control study Settings: Outpatient department, National Institute of Child Health (NICH) Duration: Six months from 26th February 2018 to 28th August 2018 Data Collection procedure: All patients age 9 to16 years of either gender were included. Cases were defined as presence of fasting plasma glucose of > to 126.0 mg/dL (7.0 mmol/L) for more than one year whereas all patients with fasting plasma glucose of less than 126 mg/dL (7.0 mmol/L) were P a g e | 2 defined as controls. The blood sample was collected in a sterile manner after an overnight fasting of 8 hours and was sent to hospital laboratory and verified by pathologist. Results: Out of total 60 patients, the mean age of the patients was 11.23 ±1.76 years. Dyslipidemia was found to be significantly higher (n=26, 86.7%) among diabetic patients as compared to non-diabetic patients (n=18, 60%). (p-value 0.020) Moreover, the risk of dyslipidemia was 4.33 times higher among diabetic patients than that of non-diabetics (OR 4.33). Patients having >10 years of age and diabetes were 8.01 times more likely (OR 8.01, p-value 0.042) and diabetic males were 8.40 times more likely (OR 8.40, p-value 0.008) to have dyslipidemia. Conclusion: Highly significant association of dyslipidemia and type 1 diabetes mellitus was found among children up to 16 years of age. Keywords: Dyslipidemia, diabetes mellitus, children

Objectives To review the data of infants and children with suspected monogenic diabetes who underwent genetic testing. Methods Monogenic diabetes is a rare form of diabetes resulting from mutations in a single gene. It can be caused by dominant as well as recessive modes of inheritance. In a country like Pakistan where interfamily marriages are common the incidence of genetic disorders is increased. As Pakistan a resource-poor country, the diagnosis of insulin-dependent diabetes is often delayed and a genetic diagnosis of monogenic diabetes is extremely difficult. Children with clinical diagnosis of monogenic and syndromic diabates were recruited and blood samples were sent for genetic analysis. Results One thousand sixty four new cases diagnosed with type 1 diabetes were registered at the National Institute of Child Health, Karachi, in the last 10 years. Of these 39 patients were selected for genetic testing who were diagnosed with diabetes/had a sibling diagnosed with diabetes before the age of nine months (n = 27) or had extra pancreatic features ( n= 12). We identified mutations in 18/27 cases diagnosed with diabetes before nine months of age. The most common genetic subtype was WolcottRallison syndrome caused by EIF2AK3 mutations (seven cases). KCNJ11 mutations were identified in two cases, ABCC8mutations were identified in four cases from three families, GCK and INS mutations were each identified in two cases, and one SLC2A2 mutation was identified in one case. A genetic diagnosis was made in 12/12 children from six families with diabetes diagnosed after the age of nine months who had extrapancreatic features. Six patients had genetically confirmed Wolfram syndrome (WFS1), three had thiamine-responsive megaloblastic anemia (SLC19A2) and three were diagnosed with histocytosis lymphadenopathy plus syndrome (SLC29A3). Conclusions Genetic testing is essential to confirm a diagnosis of monogenic diabetes which guides clinical management and future counselling. Our study highlights the importance of diagnosing monogenic diabetes in the largely consanguineously-married population of Pakistan.

OBJECTIVE To determine the clinical presentation of Addison's disease in order to increase the awareness of presentation in Pakistani children. STUDY DESIGN Observational study. PLACE AND DURATION OF STUDY Department of Diabetes and Endocrinology, National Institute of Child Health, Karachi, Pakistan, from 2015 to 2019. METHODOLOGY Sixty-three children of Addison's disease were enrolled in the study, who have visited and facilitated from the services of National Institute of Child Health from urban and rural region of the Sindh province. Diagnosis were made through biochemical analysis and detailed examination of acute and chronic symptoms. Study was initiated after taking the approval from Institutional Review Board. Moreover, written informed consents were also taken from each of the study participant. RESULTS There were 36 boys and 27 girls with a mean age at diagnosis of 3.92 and 4.96 years, respectively. Twelve patients were presented with an adrenal crisis following an acute illness. All of them had hyponatraemia; however, 10 had a hyperkalaemia and 8 had been reported with hypoglycaemia. Increased skin pigmentation was observed in 45 children with other identifiable features including weight loss, lethargy, and poor response in activities. Moreover 15 of them were identified with associated disorder (autoimmune polyendocrinopattay syndrome (APS), Allgrove or triple A syndrome, and adrenoleukodystrophy). Conclusion: Typical and atypical presentations of Addison's disease in children of Pakistani population are defined in this study which may assist in better management of Addison's patients. Key Words: Adrenal crisis, Hyponatremia, Hyperkalemia, APS, Allgrove, Adrenoleukodystrophy.

Background Diabetic ketoacidosis (DKA) is one of the most common complications of type 1 diabetes. Mortality is not uncommon in DKA, mostly in younger children with severe DKA and those complicated with cerebral edema. Early identification of high-risk patients can help in timely interventions to improve the outcome of DKA. Pediatric Risk of Mortality (PRISM III) is a standard scoring system to objectively predict the prognosis and outcome of pediatric intensive care unit (PICU) patients. Objective To predict the need for inotrope and mechanical ventilation and mortality rate using PRISM III in DKA patients admitted to PICU. Methods A prospective observational study was conducted in the PICU of the National Institute of Child Health, Karachi, from February 2020 to September 2021 involving 114 children. PRISM III scoring protocol was applied. A PRISM III score of >8 predicted higher mortality risk. Results The mean PRISM III score was 6.56 ± 3.18 with 30 (26.3%) children having a score >8. Of the 30 (26.31%) patients with >8 PRISM III scores, 14 (46.67%) needed inotropic support, 6 (20%) needed mechanical ventilation, and there were eight (26.67%) mortalities. There was no reported mortality among patients with a PRISM III score ≤8. All differences were statistically significant (p < .05). Conclusion PRISM III is a highly sophisticated scoring system that can aid clinicians in the early prediction of adverse clinical outcomes in patients with DKA. Robust scientific evidence supporting its clinical application can help practically improve the outcome of DKA in young patients.

Van Wyk Grumbach syndrome is well known for protracted hypothyroidism, characterised by multicystic ovaries (normal size ovaries contain many follicles of various sizes), isosexual precocious puberty and delayed skeletal growth. A series of ten children with Van Wyk Grumbach syndrome is been presented with their clinical features, biochemical and radiological profile and management. Patients showed a noteworthy improvement upon thyroxine therapy. It is vital to keep this entity in consideration and; hence, should investigate for thyroid status during the evaluation of ovarian cysts. Thyroxin replacement after establishing the diagnosis early can prevent the patient from going through extensive workup and surgeries. Key Words: Hypothyrodism, Multicystic ovaries, Isosexual precocious puberty.

Thiamine responsive megaloblastic anemia syndrome is a rare genetic disorder usually associated with sensorineural deafness, megaloblastic anemia, and/or diabetes mellitus due to mutations in SLC19A2, encoding a thiamine transporter protein. In this case, we report a 2.5-year-old baby boy born to consanguineous parents. He was noted to be deaf and mute during his first year of life. He was diagnosed with anemia at the age of 15 months and required blood transfusion twice. The cause of anemia was not established and it was attributed secondary to some viral infection. At the age of 2 years, he was diagnosed with DM. The diagnosis of TRMA had been made during his evaluations for uncontrolled blood glucose, sensorineural deafness, and anemia. After few weeks of thiamine replacement, his hemoglobin increased to normal values; his sugars improved but had no changes in his deafness. Analysis of all coding regions and exon/intron boundaries of the SLC19A2 gene by Sanger sequencing. A p,Leu208fs homozygous frame shift variant is identified in the SLC19A2 gene, located on the Exon 2 and DNA description is c.623dup. This variant is predicted to be pathogenic and diagnosis of TRMA syndrome is confirmed. The diagnosis of TRMA should be kept in mind in differential diagnosis of DM with anemia and or sensorineural hearing loss. Particularly in the populations where the consanguinity is frequent as diagnosis has great impact on management.

To determine the variations in peak growth hormone levels during insulin tolerance test (ITT) in diagnosis of growth hormone deficiency (GHD) in children presenting with short stature.Descriptive study.Department of Pediatric Endocrinology, National Institute of Child Health (NICH), from January to December 2018.Clinical records of all children who underwent ITT during the above mentioned period were reviewed. All 348 children of either gender from 2-17 years of age with height more than 2SD below the mean (3rd percentile) suspected GHD and subjected for ITT were included. Verbal consent was taken from all parents. Children below 2 years and with other causes of Short Stature like hypothyroid, celiac, cardiac, chronic liver, kidney diseases and syndrome were excluded.Total 348 children were subjected to ITT. Out of these 48.3% were found to have GH levels5ng/ml, 33.6% b/w 5-10 ng/ml and 18.1%10 ng/ml. Precisely peak GH levels at different time intervals are 1.1%, 19.3%, 47.4%, 29.9%, and 2.3% for 0, 30, 60, 90 and 120 minutes respectively. Mostly peak growth hormone levels were accomplished at 60 minutes followed by 90 and then at 30 minutes. Hypoglycemia was achieved 0.8%, 47%, 26%, 24% and 1% at 0, 30, 60, 90, and 120 minutes.The 0, 30, 60, and 90 minutes samples are adequate to confirm the diagnosis of GH deficiency. This shorter duration of ITT to 90 minutes is cost effective as it decreases the financial burden of unnecessary testing. Additionally, it reduces the risk of side effect like hypoglycemia. Key Words: Short stature, Growth hormone deficiency, Insulin tolerance test.

CLAN (Caring and Living as Neighbours) is an Australian-based non-governmental organisation (NGO) committed to equity for children living with chronic health conditions in resource-poor settings. Since 2004, CLAN has collaborated with a broad range of partners across the Asia Pacific region to improve quality of life for children living with congenital adrenal hyperplasia (CAH). This exploratory case study uses the Knowledge to Action (KTA) framework to analyse CLAN&rsquo, s activities for children living with CAH in the Asia Pacific. The seven stages of the KTA action cycle inform a systematic examination of comprehensive, collaborative, sustained actions to address a complex health challenge. The KTA framework demonstrates the &ldquo, how&rdquo, of CLAN&rsquo, s approach to knowledge creation and exchange, and the centrality of community development to multisectoral collaborative action across a range of conditions, cultures and countries to redressing child health inequities. This includes a commitment to: affordable access to essential medicines and equipment, education, research and advocacy, optimisation of medical management, encouragement of family support groups, efforts to reduce financial burdens, and ethical, transparent program management as critical components of success. Improvements in quality of life and health outcomes are achievable for children living with CAH and other chronic health conditions in resource-poor settings. CLAN&rsquo, s strategic framework for action offers a model for those committed to #LeaveNoChildBehind.

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.

To determine the frequency of common subtypes of juvenile idiopathic arthritis among paediatric population.The cross-sectional study was conducted at the National Institute of Child Health, Karachi, from January to June, 2010, and comprised children below 16 years of age with arthritis in one or more joints for at least 6 weeks. Physical examination was done and detailed history was recorded. When5 joints of the body were involved, it was considered polyarthritis. If4 joints were involved, it was pauciarticular arthritis.Of the 95 cases in the study, 52(54.7%) were girls and 43(45.3%) were boys, with an overall mean age of 11±1.2 years. Polyarticular arthritis was found in 51(53.7%) subjects and pauciarticular arthritis in 44(46.3%). Out of 43 boys, 27(62.8%) had pauciarticular, while 35(67.3%) of the 52 girls had polyarticular arthritis.Polyarticular arthritis was the most common sub-type. Proportion of polyarticular arthritis was high in female children, while pauciarticular arthritis was high in male children.

To determine the frequency of hyperglycemia in critically ill children admitted in PICU of a tertiary care hospital of Karachi and to compare the mortality of critically ill children with and without hyperglycemia.Cross-sectional study.Paediatrics Intensive Care Unit (PICU) of National Institute of Child Health (NICH), Karachi, from November 2011 to April 2012.One hundred fifty critically ill children admitted to PICU were included. Patients who had fasting blood sugar levels more than 126 mg/dl within 48 hours of admission were included in the hyperglycemic group. The normoglycemic and hyperglycemic groups were followed till 10 days to determine the mortality associated with hyperglycemia.Out of 150 patients, 82 (54.7%) had hyperglycemia. Mortality rate was 48.7% (n=73/150). However, mortality rate was significantly high 57.3% (n=47) in hyperglycemic patients than non-hyperglycemic patients (p=0.019).The presence of stress-induced hyperglycemia in critically ill patients is a well established marker of poor outcome, and a very high mortality rate. Normoglycemia was associated with favorable outcomes in terms of hospital stay and mortality.

To observe the frequency, demographic data and outcome of diabetic ketoacidosis (DKA) in children with established type 1 diabetes and newly diagnosed diabetes at a tertiary care hospital.The case record review was done of children admitted with the diagnosis of DKA at The National Institute of Child Health, Karachi from 1st June 2008 till 31st May 2009. All records with the diagnosis of DKA were reviewed and those children with only hyperglycaemia, or who did not fulfill the criteria of DKA were excluded. The demographic data and laboratory investigations which included blood sugar monitoring, arterial blood gases, urine analysis especially for ketones, serum electrolytes, complete blood count and blood culture 'were reviewed. The previous numbers of admissions in children with established DKA were also noted with reasons. The duration of symptoms and fluids required, time of recovery, complications, and outcome were noted and compared between those with established diabetes and children with newly diagnosed diabetes. Data was entered and analyzed on SPSS version 15.Out of 124 case records, 117 were included which fulfilled the criteria of DKA. A large number, 65 (55.5%) children were in the10 years age group with a female predominance. Out of 117 children 50 (42.7%) had established Type 1 diabetes and 67 (57.2 %) children had newly diagnosed diabetes. The commonest presenting complaints in both groups were respiratory distress (87.1%) and vomiting (77.7%). The symptoms of polyuria, polydipsia and nocturia were more among the newly diagnosed children as compared to those with established diabetes with a significant p value0.001. The comparison of clinical features and laboratory investigations of the two groups showed no difference except that those children with established diabetes improved earlier, required lesser duration of intravenous fluids and their insulin was changed to subcutaneous in less time compared with newly diagnosed children. (p0.001). The commonest complication in both groups was hypoglycaemia followed by hyponatraemia, more in newly diagnosed diabetic children.These soaring numbers are just from one center, highlighting the issue of this much neglected disease in our country. More studies on a larger scale are needed to assess the prevalence/incidence in our children and also more emphasis with educational programmes on prevention of recurrent attacks of DKA.

To determine the safety of insulin tolerance test (ITT) for assessing growth hormone (GH) deficiency in children.This hospital based study was conducted at the National Institute of Child Health, Karachi from 1st November 2008 till 30th October 2009. All children suspected of growth hormone deficiency, were included after excluding all other causes of short stature. Verbal informed consent was taken from the parents. Children less than 2 years of age, weighing less than 10 kg, untreated/inadequately treated hypothyroidism or Addison's disease, epilepsy, having history of hypoglycaemic fits or cardiac disease were excluded. All children were subjected to the international standard protocol of ITT and their samples of growth hormone and blood sugars were drawn. Complications during the procedure like hypoglycaemia, hypothermia, loss of consciousness, fits, vomiting and failure to achieve hypoglycaemia were recorded. Insulin tolerance test was performed on a total of 168 subjects. The data was entered in SPSS version 17 for analysis.A total of 168 children were subjected to the ITT. Four of them were abandoned as they could not achieve hypoglycaemia despite repeating the dose of insulin. Results were analyzed on 164 children whose mean age was 10 +/- 3.5 years, There were 96 (58%) males and 68 (41%) females. Over all 79.8% children achieved hypoglycaemia. None of the subjects developed any complication (fits, loss of consciousness,) or required intravenous glucose during the test and it was completed in all children with close monitoring. The results showed that there was a significant effect of time after insulin administration on both the blood glucose level (BG) and growth hormone (GH) levels. The blood glucose level decreased rapidly after administration of insulin and was lowest 30 minutes after injection and showed an increasing trend in subsequent readings, becoming almost equal to the baseline value 120 min after injection. From the study group 111 (66%) children were diagnosed as having growth hormone deficiency, 52 (31.3%) were normal and 1 (0.6%) had growth hormone insensitivity.ITT in children was found to be a safe and reliable test but can be potentially dangerous and requires very close monitoring and supervision and should be performed in a center with experienced staff.

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 BMI95th 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 across the insulin quartile (p0.05). 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.

Methodology This study was conducted in National Institute of Child Health at Department of Pediatrics, Division of Endocrinology from January 2008 to December 2010. A Total of 127 Patient under age of 14 years with ambiguity, micropenis, hypospadias, cryptorchism and delayed puberty were selected and studied.USG Pelvis, HCG Stimulation test and Chromosomal analysis were carried out in all patients. Two types of HCG stimulation test were performed. Short HCG was done in children ten and less than ten years of age. Prolong HCG was performed in children more than ten years of age. Laproscopy and biopsy were carried out in patients who had mullerian duct structure on USG and also in patients with no gonads. FISH analysis was done in patients who were 46XX karyotype with testes.

OBJECTIVE To determine the etiology of precocious puberty in children and to compare the clinical and laboratory parameters of central and peripheral precocious puberty. STUDY DESIGN Cross-sectional study. PLACE AND DURATION OF STUDY Endocrine Clinic at National Institute of Child Health, Karachi, from January 2009 to December 2011. METHODOLOGY 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. RESULTS 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. CONCLUSION 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.