Newborn screening in Pakistan - lessons from a hospital-based congenital hypothyroidism screening programme.

We are living in a time of unprecedented increase in knowledge and rapidly changing technology. Such biotechnology especially when it involves human subjects raises complex ethical, legal, social and religious issues. The establishment of newborn screening programmes in developing countries poses major challenges as it competes with other health priorities like control of infectious diseases, malnutrition and immunization programmes. Despite this, it is imperative that the importance of newborn screening programmes is recognised by developing countries as it has been proven through decades of experience that it saves thousands of babies from mental retardation, death and other serious complications. Pakistan has an estimated population of 167 million inhabitants, 38.3% of whom are under 15 years of age. Pakistan lacks a national programme for newborn screening. However, as individual practice at the local level, Aga Khan University Hospital (AKUH) and a few other hospitals are doing newborn screening for congenital hypothyroidism. The main hurdle in the implementation of newborn screening in Pakistan is the lack of good infrastructure for health. Eighty percent of deliveries take place at home. Moreover, little resources are available for children identified with a genetic condition due to the non-existence of genetic and metabolic services in Pakistan. In a 20-year audit of congenital hypothyroid screening at AKUH we found 10 babies with congenital hypothyroidism. However due to missing data links spanning several years, we were unable to calculate its true incidence during this period. In order to estimate the incidence of congenital hypothyroidism (CH) we reviewed in detail data over 10 months in 2008, a period where there was better compliance for repeat thyroid stimulating hormone (TSH) testing, and found 2 babies with CH. This gave an estimated incidence of 1 in 1600 live births

Spectrum of complications of severe DKA in children in pediatric intensive care unit

Objectives: To describe the spectrum of complications of Diabetic Ketoacidosis (DKA) observed in children admitted with severe DKA.Methods: Retrospective review of the medical records of all children admitted with the diagnosis of severe DKA in Pediatric Intensive Care Unit (PICU) of the Aga Khan University Hospital, from January 2010 to December 2015 was done. Data was collected on a structured proforma and descriptive statistics were applied.Results: Total 37 children were admitted with complicated DKA (1.9% of total PICU admission with 1.8% in 2010 and 3.4% in 2015). Mean age of study population was 8.1±4.6 years and 70% were females (26/37). Mean Prism III score was 9.4±6, mean GCS on presentation was 11±3.8 and mean lowest pH was 7.00±0.15. Complications observed included hyperchloremia (35.94%), hypokalemia (30.81%), hyponatremia (26.70%), cerebral edema (16.43%), shock (13.35%), acute kidney injury (10.27%), arrhythmias (3.8%), and thrombotic thrombocytopenic purpura (5.4%), while one patient had myocarditis and ARDS each. 13/37 children (35%) needed inotropic support, 11/37 (30%) required mechanical ventilation while only one patient required renal replacement therapy. Two patients (5.4%) died during their PICU stay.Conclusions: Hyperchloremia and other electrolyte abnormalities, cerebral edema and AKI are the most common complications of severe DKA

Use of miltefosine in the treatment of visceral leishmaniasis in children at a tertiary care hospital of Karachi

Existing standard treatment options for visceral leishmaniasis are less than optimal. We report here the use of oral miltefosine in the treatment of two paediatric cases of visceral leishmaniasis at a tertiary care hospital in Karachi, Pakistan. One patient came from Balochistan while the second patient was from Northern Pakistan. Both presented with a prolonged history of fever, massive hepatosplenomegaly, anaemia and thrombocytopenia. Visceral leishmaniasis was diagnosed with bone marrow studies. Amphotericin B was first started in the first patient; however severe hypokalaemia and allergic reaction occurred. Oral miltefosine was then administered. The child showed clinical improvement with regards to signs of leishmania infection but succumbed to a nosocomial infection during the hospital stay. In the second patient, miltefosine was started in the first instance. He showed remarkable clinical improvement. At 2 months follow-up, the child showed adequate weight gain along with successful resolution of hepatosplenomegaly and fever. Miltefosine has the potential to be considered a first line therapy for visceral leishmaniasis in developing countries; however larger studies are warranted to validate the trends observed in this small case series

Frequency of hypocalcemic fits in children 2 months to 2 years of age, presenting with the first episode of afebrile seizures at hospital settings in urban Pakistan: A cross-sectional study

Introduction: Seizures are common in the pediatric age group, occurring approximately 10% of children. Hypocalcemia is one of the most common metabolic causes of afebrile seizures. The objective of the study was to determine the frequency of hypocalcemic fits in children presenting with the first episode of afebrile seizures from 2 months to 2 years of age. Methods: The study was conducted at the Aga Khan hospital Karachi and its three secondary hospitals including the following sites of Kharadar, Hyderabad, and garden. It was a cross-sectional study. The duration of the study was of 6 months from 18th July 2017 to 18th Jan. 2018. All patients who fulfill the inclusion criteria and visited the Pediatric medicine Department of Aga Khan Hospital, Karachi, and its secondary hospitals were included in the study after ethical approval and informed and written consent. A brief history was taken, clinical examination was done and serum calcium level was sent to the institutional laboratory to reach the outcome i.e. hypocalcemic fits. Result: A total of 85 children presenting with the first episode of afebrile seizures were included. Total of 45 patients (52.98%) were males & 40 patients 2 (47.1%) were females with the mean age were 10.5824 ± 6.84907 months. The hypocalcemic fits were seen in 21 children (24.7%). Discussion: Hypocalcemia is a common cause of afebrile fits in children. Inadequate sun exposure, early age, male gender, low weight, and illiteracy are major risk factors for hypocalcemia

Non O1, non O139 vibrio cholerae bacteraemia in an infant; case report and literature review

Non 01, Non O139 Vibrio cholerae bacteraemia is a rare but potentially fatal occurrence. There have been very few incidents of this infection from around the world. The treatment regimen of antibiotics also varies in literature. We present a case of bacteraemia caused by Non O1, Non O139 Vibrio cholerae along with associated risk factors, disease manifestations, laboratory diagnosis and treatment regimen. This serves to add additional information regarding symptoms and signs of this infection along with management of patient. Knowledge regarding this topic shall be highly useful to professionals if further cases are detected. In the discussion section, a review of literature of previous cases is also presented

Mabry syndrome in a child of South Asian descent

Mabry syndrome is the triad of seizures, hyperphosphatasia, and mental disability. It usually manifests in first year of life and has an autosomal recessive mode of inheritance. Besides the usual triad, other manifestations of Mabry syndrome include hypoplasia of distal phalanges, brachytelencepahly, gastrointestinal malformations and constipation, hypertelorism, short nose with a broad nasal bridge and dip, and thin upper lip with down turned corners of the mouth. More than 20 cases of Mabry syndrome have been reported in medical literature. Herein, we report the case of a six-month child with Mabry syndrome that presented with decreased neck holding, hypotonia and delayed motor milestones. The child also had a high-arched palate and hyperplastic malar eminences. Constipation was present but had a delayed onset, starting at 19 months of age. This is the first case of Mabry syndrome occurring in a child of South Asian descent

Clinical profile and outcomes of paediatric patients with diabetic ketoacidosis at a tertiary care hospital in Pakistan

OBJECTIVES: This study aims to present an experience in the management and clinical features of 88 children presenting with diabetic ketoacidosis (DKA) from Pakistan. METHODS: A retrospective medical chart review of all patients, \u3c or = 15 years of age, who presented to the Aga Khan University Hospital, Karachi, Pakistan in the last ten years with a diagnosis of diabetic ketoacidosis was carried out. Severity of DKA was defined as mild (venous pH \u3c 7.30 or bicarbonate=15mEq/l), moderate (venous pH \u3c 7.2 or bicarbonate = 10 mEq/l) and severe (venous pH \u3c 7 or bicarbonate \u3c 5 mEq/l). These classes correspond to 1st, 2nd and 3rd degrees of diabetic ketoacidosis severity respectively. Cases in which diabetic ketoacidosis had occurred at onset of diabetic diagnosis were not included in the study. RESULTS: Mean age was 7.5 +/- 3.6 years; 58 (66%) patients were male. Twenty six patients had mild diabetic ketoacidosis, 44 had moderate while 18 had severe diabetic ketoacidosis at the time of presentation. Severity of diabetic ketoacidosis was significantly associated with the presence of infection, history of omission of insulin, poor compliance, presence of shock at time of presentation, length of stay in the hospital, final outcome (p \u3c 0.01 for each of these associations) and Glasgow Coma Scale score (p = 0.02). Mortality in this series was 3.4%. CONCLUSION: Poor compliance was associated with the severity of diabetic ketoacidosis. Paediatric endocrinologists\u27 should ensure that patients and their parents understand the importance of the need for regular insulin injections and regular monitoring of blood glucose

Complementary feeding pattern and nutritional status of children

Objective: To determine the complementary feeding patterns and their association with malnutrition. Study design: Prospective observational study. Place and Duration of the Study: Outpatient clinics of Aga Khan University Hospital, Pakistan, from June to November 2019. Methodology: A total of 207 children from age six to twenty-four months, who presented in the outdoor clinics of the study place, were enrolled. Data were recorded in a predesigned data sheet adopted from the infant and young child feeding module. Chi-square test was applied post-stratification and a p-value of Results: Among a total of 207 children, 115 (55.6%) were males and 92 (44.4%) were females, with a mean age of 14.15 ± 5.6 months. Complementary feeding was started at an appropriate age in 124 (60%) children. Normal weight was seen in 133 (64.3%) children, while 73 (35.3%) were underweight. Stunting was presented in 44 (21.3%) children, whereas 163 (78.7%) children were of normal length. The most common reason for early initiation of complementary feeding was difficulty in continuing to breastfeed (n=50, 24.2%); the most common reason behind late complementary feeding was bottle feeding (n=45, 21.7%). Conclusion: Only sixty percent of mothers living in an urban setting started complementary feeding at an appropriate age. Various myths are counteracting complementary feeding practice

Adrenal insufficiency in a child with MELAS syndrome

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) are established subgroups of mitochondrial encephalomyopathy. m.3243A \u3e G a common point mutation is detected in tRNA in majority of patients with MELAS phenotype whereas m.8344A \u3e G point mutation in tRNA is observed, in MERRF phenotype. Adrenal insufficiency has not been reported in mitochondrial disease, except in Kearns-Sayre Syndrome (KSS), which is a mitochondrial deletion syndrome. We report an unusual presentation in a five year old boy who presented with clinical phenotype of MELAS and was found to have m.8344A \u3e G mutation in tRNA. Addison disease was identified due to hyperpigmentation of lips and gums present from early childhood. This is the first report describing adrenal insufficiency in a child with MELAS phenotype

Longitudinal changes in body mass index in children with craniopharyngioma

Objective: We investigated the relationship of body mass index at presentation and pituitary status with long-term changes in BMI over a period of 5 years. Study Design: Craniopharyngioma patients (n = 25) attending a tertiary pediatric endocrine center were divided into three groups based on their BMI at presentation [BMI ≥2 standard deviation scores (SDS), 0-1.99 SDS, and <0 SDS) and then analyzed for trends of BMI over a period of up to 5 years. Results: Median (interquartile range) BMI SDS and hypopituitarism at presentation versus at the 5-year follow-up were as follows: BMI SDS ≥2 group (n = 10): 3.55 (0.68), 6/10 versus 3.76 (1.13), 8/10; BMI SDS 0-1.99 group (n = 11): 1.68 (1.05), 3/11 versus 1.64 (2.04), 7/11, and BMI SDS <0 group (n = 4): -0.23 (0.93), 2/4 versus 0.61, 4/4. At the 5-year follow-up, 10/10, 7/11, and 1/4 subjects when divided in groups according to BMI at presentation were obese. Conclusions: Our data indicate that obesity at presentation, rather than panhypopituitarism either at or after presentation, predicts obesity 5 years after diagnosis. However, obesity at presentation is not always associated with the subsequent development of panhypopituitarism. Pediatric craniopharyngioma subjects who have BMI SDS ≥2 at presentation require early and aggressive intervention to help prevent the complications of obesity