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.

Preference of the patient's family for family-centred care in a paediatric hospital.

Objective: To explore the dimensions of family-centred care preferred by families of paediatric inpatients in a public healthcare setting. METHODS: The qualitative study was conducted at the National Institute of Child Health, Karachi, from October 2021 to August 2022, and comprised family members of the hospitalised children. Data was collected through three focus group discussions that were guided by a semi-structured questionnaire. Using the five-step Fereday and Muir-Cochrane guidelines, data was coded and subjected to thematic analysis. RESULTS: Of the 21 subjects, 13(62%) were males and 8(38%) were females. The overall mean age was 32.24±7.58 years (range: 18-50 years). In terms of relationship with the patient, 9(43%) were fathers and 6(28.6%) were mothers. Each focus group discussion had 7(33.3%) subjects. Thematic analysis showed that the participants perceived family-centred care positively. Eight categories emerged depicting family perception and experience of family-centred care in a tertiary-care setting. Conclusion: The participants perceived family-centred care respectful and empathic towards patients' families, making them integral care team members.

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.

Celiac And Autoimmune Thyroid Disease In Patients With Anti-Gad Positive Type-1 Diabetes Mellitus.

BACKGROUND: Type-1 diabetes mellitus (T1DM) and autoimmune thyroid disease can occur concomitantly and patients with TIDM have a high risk of other autoimmune conditions like thyroid disease and celiac disease. This study aimed to analyze the association of anti-GAD positive T1DM with anti-thyroid antibodies and celiac disease. METHODS: This cross-sectional study was conducted at the Department of Paediatric Endocrinology & Diabetes, National Institute of Child Health, Karachi Pakistan from July 2022 to December 2022. A total of 115 children of both genders aged between 1-18 years having known T1DM were analyzed. Children with chronic kidney disease or chronic liver disease were excluded. Those children were also not included whose parents/caregivers did not wish their children to be part of this research. The blood sample of each child was taken in a sterilized container and sent to an institutional laboratory for biochemical investigations. RESULTS: In a total of 115 patients, 67 (58.3%) were female and 48 (41.7%) males. The mean age was 8.87±3.43 (ranging between 1.5-17 years). The mean HbA1c was 11.86±7.31%. It was found that anti-GAD IgG was having signification association with celiac disease (p<0.001). Significant correlation of anti-GAD positive antibodies with Ttg-IgG antibodies (correlation coefficient=0.303, p=0.001), thyroid peroxidase antibodies (correlation coefficient=0.228, p=0.001). CONCLUSIONS: High proportions of children with anti-GAD positive T1DM patients were found to have thyroid disorders and celiac disease. A significant correlation was found between anti-GAD positive antibodies, celiac disease and anti-thyroglobulin antibodies.

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).

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.

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.

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.

Frequency, causes and outcome of neonates with respiratory distress admitted to Neonatal Intensive Care Unit, National Institute of Child Health, Karachi.

OBJECTIVE: To determine the frequency, aetiology and outcome of respiratory distress in neonates in intensive care unit. METHODS: The descriptive cross-sectional study was conducted at the Neonatal Intensive Care Unit, National Institute of Child Health, Karachi, from October 2009 to March 2010. It comprised neonates aged day 0 to 28 who were admitted to Neonatal Intensive Care Unit. The neonates were screened first for respiratory distress and presence of one or more signs and symptoms. History, examination and investigations were carried out to find out various aetiologies of respiratory distress. Outcome was measured in terms of discharge and death. Data was analysed using SPSS12. RESULTS: Of the 205 neonates in the study, 120(58.6%) were boys and 85(41.4%) were girls The overall mean age was 70.58±110.02 hours and the mean gestational age was 36.32±2.72 weeks while the mean weight was 2.41±2.4kg. Respiratory rate >60/min was found in all (100%) the neonates. In terms of signs and symptoms, 125(60.9%) had grunting, 205(100%) had subcostal retractions and nasal flaring, and 81(40%) had cyanosis. The aetiologies observed were birth asphyxia, sepsis, transient tachypnoea of the newborn, pneumonia, meconium aspiration syndrome and respiratory distress syndrome in 22(10.75%), 37(18.05%), 29(14.1%), 36(17.6%), 34(16.7%) and 47(23.0%) neonates respectively. The incidence of neonates with respiratory distress was 68(33.3%). CONCLUSIONS: The frequency of respiratory distress among the neonates was high, while mortality was high in neonates with respiratory distress, especially in pre-term and low birthweight neonates. Early diagnosis and management is important for better outcome.