Frequency of C-peptide and antibody levels (anti GAD, Islet cell antibodies, insulin auto antibodies) in children of Pakistan with Type-1 diabetes.

Background and Objective: The autoimmune mechanism in T1DM causes gradual loss of pancreatic ß-cell, which progresses to hyperglycemia and ultimate reliance on consistent insulin therapy. T1DM has been the commonest type of diabetes in children and this study will help in refining indulgent towards the problem and its pathophysiology in our people. The objective was to find out the prevalence of C-peptide and antibody levels (anti GAD, ICA, IAA and IA2) in children and adolescents of Pakistan with T1DM. Methods: We conducted this cross-sectional study at Department of Pediatric Endocrinology, National Institute of Child Health, Karachi between August 2019 to February 2020 and included 98 children who had T1DM for more than one month. Subjects whose GFR was <30ml/min were omitted from the study. Among those registered subjects, C-peptide, human islet cell antibody (ICA), insulin auto antibodies (IAA) and anti-glutamic acid decarboxylase were assessed. Demographical and laboratorial facts were noted on a pre-constructed proforma. Results: There were 77(78.3%) cases who had level of C-peptide <0.8 and anti-GAD was found in 47(48%) subjects. 35(35.7%) cases found positive for IA2 .and 7(7.1%) patients had insulin auto antibodies positive while ICA was negative in total 98(100%) subjects. Conclusion: Children with T1 DM possessed increased levels of anti-GAD antibodies, insulin autoantibodies and anti (IA2) but islet cells antibodies were negligible in our population when checked at a point of time. C-peptide may be normal in some, but its level declines with long duration of diabetes in children.

Gonadotropin independent sexual precocity in a Pakistani male infant from an activating mutation in LHCGR gene.

A male child, aged seven months, visited the out patients clinic of the National Institute of Child Health, Karachi, in May 2020 with the features of iso-sexual puberty. After ruling out the more common causes of early puberty, like congenital adrenal hyperplasia and tumours secreting chorionic gonadotropin hormone, hormonal assessment indicated raised testosterone independent of gonadotropin. The volume of the testicles was symmetric and testicular ultrasonography revealed no mass. Genetic analysis for the LHCGR gene was performed for confirmation which revealed activating heterozygous missense pathogenic mutation in c.1732G>T (p.Asp578Tyr). This is the first reported case of testotoxicosis (FMPP) from Pakistan which was genetically confirmed.

Early suspicion can save lives; mucormycosis in two children with diabetic ketoacidosis in Pakistan.

Mucormycosis is a cause of fulminant necrotising fungal infection in children with underlying immunocompromising conditions. Rhino-orbito-cerebral infection is its most common form in the paediatric group with uncontrolled diabetes mellitus or diabetic ketoacidosis. The initial presentation can mimic a bacterial infection; thus a high index of suspicion is needed for timely intervention to reduce morbidity and mortality. We have presented a case of rhino-orbito-cerebral mucormycosis (ROCM) in two patients with diabetic ketoacidosis for the first time from Pakistan. Both the patients couldnot survive due to extensive disease on late presentation.

Perceptions of parents and religious leaders regarding minimal invasive tissue sampling to identify the cause of death in stillbirths and neonates: results from a qualitative study.

BACKGROUND: Recently, the minimal invasive tissue sampling (MITS) procedure has been developed to support determination of the cause of death as an alternate to conventional autopsy, especially in countries where complete diagnostic autopsy is not routine. To assess the feasibility of implementation of the MITS procedure for a study to determine cause of death in premature births and stillbirths in south Asia, we explored the views and perceptions of parents and religious leaders on the acceptability of MITS. METHODS: A qualitative study was conducted at the National Institute of Child Health (NICH) hospital of Karachi, Pakistan. Focus group discussions (FGDs) were conducted with parents of newborns who visited well-baby clinics of the NICH hospital for post-natal check-ups. Key-informant interviews (KIIs) were conducted with religious leaders. Data were analyzed using NVivo 10 software. RESULTS: A total of 13 interviews (FGDs = 8; KIIs = 5) were conducted. Three overarching themes were identified: (I) acceptability of MITS; (II) concerns affecting the implementation of MITS; and (III) religious and cultural perspectives. Participants' acceptance of MITS was based on personal, religious, cultural and social beliefs. Parents widely recognized the need for this procedure in cases where the couple had experienced multiple stillbirths, neonatal deaths and miscarriages. Counseling of parents was considered vital to address emotional concerns of the parents and the family. Religious leaders indicated acceptability of the MITS procedure from a religious perspective and advised that respect for the deceased and consent of the guardians is mandatory when performing MITS. CONCLUSIONS: This qualitative study provided a unique opportunity to understand the views of parents and religious leaders towards the use of MITS. Generally, MITS appears to be an acceptable method for identifying the cause of death in neonates and stillbirths, provided that the deceased is respected and buried as soon as possible without any delays and parents are counseled appropriately. Findings from this research are essential in approaching families for consent for MITS.

Perceptions of parents and healthcare professionals regarding minimal invasive tissue sampling to identify the cause of death in stillbirths and neonates: a qualitative study protocol.

BACKGROUND: Globally, around 2.6 million neonatal deaths occur world-wide every year and the numbers of stillbirths is almost similar. Pakistan is ranked among the highest countries in the world for neonatal mortality. In 2016, for every 1000 babies born in Pakistan, 46 died before the end of the first month of life. Also, Pakistan had the highest rate of stillbirths (43.1/1000 births) in 2015. To meet sustainable development (SDG) targets of reducing neonatal mortality and stillbirths, it is essential to gain understanding about the causes of neonatal death and stillbirths. In Pakistan, full autopsies are conducted only in medico-legal cases and are very rarely performed to identify a definitive cause of death (CoD) and because of cost and insufficient staff are generally not feasible. Recently, minimally invasive tissue sampling (MITS) has been used to determine CoD in neonates and stillbirths as it addresses some of the socio-cultural and religious barriers to autopsy. However, it is not known how families and communities will perceive this procedure; therefore, exploring family and healthcare professionals' perceptions regarding MITS is essential in determining acceptable and feasible approaches for Pakistan. METHODS: The study will employ an exploratory qualitative research design. The study will be conducted at the National Institute of Child Health (NICH) hospital of Karachi. The data collection method will consist of key-informant interviews (KIIs) and focus group discussions (FGDs). FGDs will be conducted with the families and relatives of newborns who are visiting the outpatient department (OPD) and well-baby clinics of NICH hospital. KIIs will be conducted with the NICH - medical director, healthcare providers, professionals involved in proceedings related to death and dying, religious leaders, health sector representatives from the government, public health experts, maternal and child health (MCH) specialists, obstetricians and neonatologists and experts from the bioethics committee. Study data will be analyzed using NVivo 10 software. DISCUSSION: The research will help explore specific cultural, religious and socio-behavioral factors that may increase or decrease the acceptability of MITS for identifying COD in neonates and stillbirths. The findings of the qualitative study will provide a better understanding of parents' and healthcare professionals' attitudes towards the use of MITS on neonatal deaths and stillborns.

A cross sectional study on juvenile idiopathic arthritis in paediatric population.

OBJECTIVE: To determine the frequency of common subtypes of juvenile idiopathic arthritis among paediatric population. METHODS: 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. When >5 joints of the body were involved, it was considered polyarthritis. If <4 joints were involved, it was pauciarticular arthritis. RESULTS: 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. CONCLUSIONS: 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.

Precipitating Factors and Outcome of Diabetic Ketoacidosis among Children and Adolescents with Type-1 Diabetes Mellitus.

OBJECTIVE: To determine the precipitating factors and outcomes of diabetic ketoacidosis (DKA) among patients with type 1 diabetes mellitus. STUDY DESIGN: An analytical study. Place and Duration of the Study: Department of Paediatrics, National Institute of Child Health, Karachi, Pakistan, from July to December 2022. METHODOLOGY: Children of either gender aged up to 18 years and presenting with DKA with a known diagnosis of type-1 diabetes were enrolled. Demographic, clinical, and anthropometric characteristics of all children were noted. Laboratory investigations were sent to the institutional laboratory. Presenting features, precipitating factors, severity of DKA, and outcomes noted. RESULTS: Among 131 children, 101 (77.1%) were girls. The socio-economic status of 75 (57.3%) patients was the lower middle. Celiac disease was the commonest associated disease noted in 23 (17.6%) patients. A total of 123 (93.9%) children were using basal plus bolus types. Adherence to diabetes-related drug therapy was seen in 105 (80.2%) patients. At the time of presentation, vomiting, fever, abdominal pain, and respiratory distress were the most frequent presenting features reported in 77 (58.8%), 67 (51.1%), 42 (32.1%), and 34 (26.0%) patients, respectively. The most common precipitating factors for DKA were infection/illness (n=90, 68.7%) and missed insulin dose (n=16, 12.2%); no cause was identified in 25 (19.1%) patients. The mean duration of hospital stay was 5.25±2.4 days. Four patients could not survive. CONCLUSION: The most common precipitating factor for the current episode of DKA were infection or illness, or missed insulin dose. Vomiting, fever, abdominal pain, and respiratory distress were the most frequent presenting features. In-hospital mortality was found to be 3% in DKA patients. KEY WORDS: Diabetic ketoacidosis, Type-1 diabetes mellitus, Insulin, Vomiting, Abdominal pain.

Thiamine-Responsive Megaloblastic Anaemia With Hypothyroidism, A Puzzling Association.

Background: Thiamine-responsive megaloblastic anaemia (TRMA) is characterized by the classic trio of diabetes mellitus, sensorineural hearing loss, and megaloblastic anaemia, typically emerging subtly between infancy and adolescence. Administration of high-dose thiamine often yields improvements in anaemia and occasionally in diabetes. Uncommon manifestations include optic atrophy, congenital heart defects, short stature, and stroke. In this specific case, a 5-year-old diagnosed with insulin-dependent diabetes mellitus (IDDM) since the age of one presented with symptoms such as polyuria, fever, and vomiting, revealing an HbA1c of 10.64. Further examinations disclosed compromised hearing and vision. A negative antibody workup and a thyroid profile indicating hypothyroidism prompted additional investigations, including Brainstem Evoked Response Audiometry (BERA) and retinal examination, confirming bilateral sensorineural hearing loss and maculopathy, respectively. A comprehensive blood count unveiled megaloblastic anaemia. Genetic profiling confirmed a homozygous mutation in the SLC19A2 gene, thus diagnosing TRMA. An early diagnosis, coupled with genetic confirmation, enables timely intervention, with patients responding positively to high-dose thiamine. Genetic counselling plays a pivotal role in enlightening families about the disease and its inheritance patterns, fostering awareness and understanding.

A Rare Skeletal Dysplasia-Close Mimicker Of Juvenile Idiopathic Arthritis-Progressive Pseudorheumatoid Dysplasia.

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.

Safety and Efficacy of Zoledronic Acid in children with Osteogenesis Imperfecta.

OBJECTIVE: To evaluate the efficacy and safety of zoledronic acid in children with osteogenesis imperfecta (OI). STUDY DESIGN: Descriptive Study. PLACE AND DURATION OF STUDY: National Institute of Child Health, Department of Endocrine and Diabetes, Karachi, Pakistan, from January 2011 to December 2020. METHODOLOGY: Children, with OI registered for the treatment, were included. Zoledronic acid was given to them by intravenous infusion over 30 minutes with a dose of 0.05 mg/Kg/day for a median duration of 60 (24-96) months. To ensure safety, patients were kept for 24 hours after dose administration to monitor any short-term side effects. The patients were assessed after every 3-6 months for frequency of fracture, bone pain, and BMD. RESULT: Out of 82 children [40 females (48.8%) and 42 males (51.2%)], 11 patients (13.4%) had fever and 2 patients (2.4%) had flu-like illness. No other side effects were observed. The annual fracture rate decreased overall from 2.8±1.5 to 0.2±0.5 (˂0.001) in both males (2.6±1.3 to 0.1±0.4) and females (3.1±1.7 to 0.2±0.6). Z-score on DEXA scan showed improvement in BMD overall (-3.9±2.0 to 2.2 ±1.7), in males (-3.7±1.9 to -2.1±1.7) and in females (4.1±2.1 to -2.3±1.8). There were no other long-term side effects like ocular problems, osteonecrosis of the jaw, and delayed healing of the fractures. CONCLUSION: Zoledronate use in children is associated with minimal short-term and long-term side effects with a significant improvement in BMD and decline in fracture rate. KEY WORDS: Osteogenesis imperfecta (OI), Bisphosphonates (BPs), DEXA scan, Bone mineral density (BMD).

Hyperinsulinemia and waist circumference in childhood metabolic syndrome.

OBJECTIVE: 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. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: The Endocrine Clinic of National Institute of Child Health, Karachi, from November 2005 till May 2008. METHODOLOGY: 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. RESULTS: 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 (p < 0.05). The most noteworthy anthropometric and metabolic abnormality were the waist circumference (46.5%) and insulin levels (58%) respectively. CONCLUSION: 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.

Safety of insulin tolerance test for the assessment of growth hormone deficiency in children.

OBJECTIVE: To determine the safety of insulin tolerance test (ITT) for assessing growth hormone (GH) deficiency in children. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Peak Growth Hormone Level Variability during Insulin Tolerance Test in Children with Short Stature.

OBJECTIVE: 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. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Pediatric Endocrinology, National Institute of Child Health (NICH), from January to December 2018. METHODOLOGY: 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. RESULTS: Total 348 children were subjected to ITT. Out of these 48.3% were found to have GH levels <5ng/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. CONCLUSION: 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.

Monogenic diabetes in Pakistani infants and children: challenges in a resource poor country.

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.

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

OBJECTIVE: To evaluate the effect of diabetes self-management education (DSME) on glycaemic control (HbA1c) in Pakistani children suffering from type-1 diabetes mellitus. STUDY DESIGN: Quasi-experimental study. PLACE AND DURATION OF STUDY: This study was conducted at the Diabetic OPD of National Institute of Child Health, Karachi, from April to September 2009. METHODOLOGY: 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. RESULTS: 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. CONCLUSION: In the studied group, DSME programs helped to improve glycaemic control. It should be an integral part of patient treatment in diabetic care setups.

Frequency, clinical characteristics and outcome of diabetic ketoacidosis in children with type-1 diabetes at a tertiary care hospital.

OBJECTIVE: 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. METHODS: 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. RESULTS: Out of 124 case records, 117 were included which fulfilled the criteria of DKA. A large number, 65 (55.5%) children were in the > 10 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 value <0.001. 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. (p < 0.001). The commonest complication in both groups was hypoglycaemia followed by hyponatraemia, more in newly diagnosed diabetic children. CONCLUSION: 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.

Van Wyk Grumbach Syndrome.

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.

Spectrum of Addison's Disease in Children.

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.

Perceptions of health professionals regarding minimally invasive tissue sampling (MITS) to identify the cause of death in stillbirths and neonates: results from a qualitative study.

BACKGROUND: Pakistan is considered to be one of the riskiest places in the world for childbirth as measured by its high stillbirth and neonatal mortality rates. Complete diagnostic autopsy remains the gold standard to determine the cause of death (CoD); however, it is not routinely implemented due to religious objections, sociocultural beliefs, limited resources and low demand from physicians and families. Recently, minimally invasive tissue sampling (MITS) using needle biopsies of multiple tissues to obtain tissue for histological examination and organism identification with PCR has been developed and promoted to determine CoD in low-resource areas. To ensure successful implementation of MITS, it is important to understand health professionals' attitudes and perceptions related to MITS. METHODS: A qualitative study was conducted at the National Institute of Child Health (NICH), Karachi, Pakistan. Focus group discussions (FGDs) and Key-informant interviews (KIIs) were conducted with health professionals including doctors, nurses, trainees, clinicians, bioethics experts and public health experts to explore their perceptions and views on acceptability of MITS. Data were analyzed using NVivo 10 software. RESULTS: A total of 12 interviews (FGDs = 4; KIIs = 8) were conducted. Four overarching themes were identified: (I) acceptability of MITS; (II) perceived benefits of the MITS procedure; (III) factors facilitating the implementation of MITS; and (IV) health system requirements for implementing the MITS procedure. Generally, MITS was considered as a positive development for the health system. Diagnostic accuracy and identification of less common causes of death were highlighted as two main benefits of the MITS procedure. The study highlighted a number of facilitators for the acceptability of MITS including effective counseling, building trust with parents, fast procedure time, and approaching families within a few hours of death. In addition, lack of skilled staff, poorly equipped healthcare facilities and the potential high cost to conduct MITS were identified as challenges for the implementation of MITS. CONCLUSIONS: This formative research provided a unique opportunity to explore health professionals' views and attitudes towards the MITS procedure. Such insights are crucial to ensure successful implementation and integration of a new technique into the existing health system. The research identified the factors influencing the acceptability of MITS among health professionals in Pakistan. The study also informed factors that could help facilitate the implementation of the MITS procedures in the context of Pakistan and similar settings.

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.