Novel variants underlying autosomal recessive intellectual disability in Pakistani consanguineous families.

Background: Intellectual disability (ID) is both a clinically diverse and genetically heterogeneous group of disorder, with an onset of cognitive impairment before the age of 18 years. ID is characterized by significant limitations in intellectual functioning and adaptive behaviour. The identification of genetic variants causing ID and neurodevelopmental disorders using whole-exome sequencing (WES) has proven to be successful.

A descriptive study of double burden of malnutrition in mothers of children with severe acute malnutrition admitted in Children Hospital and Institute of Child Health, Multan.

Objective: To assess the nutritional status of mothers of severely malnourished children, and to evaluate the factors associated with inadequate caloric intake of children with severe acute malnutrition versus sufficient caloric intake by mothers.

Methods: The cross-sectional descriptive study was conducted from January to June 2016 at Children Hospital and Institute of Child Health, Multan, Pakistan, and comprised mothers of severely malnourished children admitted for treatment. Data was collected using a questionnaire administered through interviews.

Malposition of left atrial disc and feasibility of recapturing Figulla-II Occlutech septal occluder.

We report a case of Figulla-II Occlutech septal occluder malposition with residual shunt at posteriosuperior margin of an atrial septal defect. Improvising its bioptome type delivery cable, same system was used to recapture the device and redeploy it successfully. This report highlights a potential malfunction of Figulla-II Occlutech disc and the advantage of its delivery system for retrieval of the device.

Whole exome sequencing identified ATP6V1C2 as a novel candidate gene for recessive distal renal tubular acidosis.

Distal renal tubular acidosis is a rare renal tubular disorder characterized by hyperchloremic metabolic acidosis and impaired urinary acidification. Mutations in three genes (ATP6V0A4, ATP6V1B1 and SLC4A1) constitute a monogenic causation in 58-70% of familial cases of distal renal tubular acidosis. Recently, mutations in FOXI1 have been identified as an additional cause.

Renal Involvement in Children with Dengue Fever: A Study in Tertiary Care Hospital of Bangladesh.

: Dengue has emerged globally as the most relevant viral infection transmitted by a mosquito bite and represents a major threat to public health. Dengue-related renal manifestations such as proteinuria, hematuria, acute kidney injury (AKI), and rhabdomyolysis are not uncommon, and acute kidney injury (AKI) is a serious complication of dengue fever. There is relatively few data on the renal manifestations of dengue fever in children.

Polymorphism of Interleukin-10 (IL-10, -1082 G/A) and Interleukin-28B (IL-28B, C/T) In Pediatric Acute Lymphoblastic Leukemia (ALL).

We conducted genotypic analyses of interleukin-10 (IL-10) (-1082 G/A; GG, GA, AA) and interleukin-28B (CC, CT, TT) genes polymorphisms in acute lymphoblastic leukemia (ALL) pediatric patients in descriptive study to evaluate the prevalence of these mutations. In amplification refractory mutation system-PCR (ARMS-PCR), one reaction was carried out for each patient's DNA sample. For IL-28B gene, two forward and two reverse primers specific for C-allele and T-allele were used separately.

Yield of comparative genomic hybridization microarray in pediatric neurology practice.

Objective: The present study investigated the diagnostic yield of array comparative genomic hybridization (aCGH) in a large cohort of children with diverse neurologic disorders as seen in child neurology practice to test whether pathogenic copy number variants (CNVs) were more likely to be detected in specific neurologic phenotypes.

Methods: A retrospective cross-sectional analysis was performed on 555 children in whom a genetic etiology was suspected and who underwent whole-genome aCGH testing between 2006 and 2012. Neurologic phenotyping was performed using hospital medical records.

Energy and protein requirements for children with CKD stages 2-5 and on dialysis-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce.

Dietary management in pediatric chronic kidney disease (CKD) is an area fraught with uncertainties and wide variations in practice. Even in tertiary pediatric nephrology centers, expert dietetic input is often lacking. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, was established to develop clinical practice recommendations (CPRs) to address these challenges and to serve as a resource for nutritional care.

A Study on Childhood Epilepsy among Traders in Benin City Nigeria.

Background: Epilepsy is a serious childhood disease associated with stigmatization in the community. Despite the deleterious effect of the disease on childhood brain growth and development, the disease is treatable.

Objective: The aim of this study is to document the knowledge of childhood epilepsy by community members using traders (market women and men in a popular market in Benin City, Nigeria) as a case study.

Inborn errors of metabolism leading to neuronal migration defects.

The development and organisation of the human brain start in the embryonic stage and is a highly complex orchestrated process. It depends on series of cellular mechanisms that are precisely regulated by multiple proteins, signalling pathways and non-protein-coding genes. A crucial process during cerebral cortex development is the migration of nascent neuronal cells to their appropriate positions and their associated differentiation into layer-specific neurons.

TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities.

The redox state of the neural progenitors regulates physiological processes such as neuronal differentiation and dendritic and axonal growth. The relevance of endoplasmic reticulum (ER)-associated oxidoreductases in these processes is largely unexplored. We describe a severe neurological disorder caused by bi-allelic loss-of-function variants in thioredoxin (TRX)-related transmembrane-2 (TMX2); these variants were detected by exome sequencing in 14 affected individuals from ten unrelated families presenting with congenital microcephaly, cortical polymicrogyria, and other migration disorders.

Clinical Efficacy and Safety of Injectable Levetiracetam Versus Phenytoin as Second-Line Therapy in the Management of Generalized Convulsive Status Epilepticus in Children: An Open-Label Randomized Controlled Trial.

Background And Purpose: There is sparsity of quality evidence for the use of drugs after first-line benzodiazepines in convulsive status epilepticus in children. The aim of the study was to compare the clinical efficacy and safety of intravenous levetiracetam versus intravenous phenytoin as second-line drugs in the management of generalized convulsive status epilepticus in children.

Methods: This open-label randomized controlled trial was conducted in the Emergency Department of The Children's Hospital and The Institute of Child Health, Multan, Pakistan over a period of 4 years and 6 months from January 2014 to June 2018.

Genetic Analysis of Tyrosinemia Type 1 and Fructose-1, 6 Bisphosphatase Deficiency Affected in Pakistani Cohorts.

Inborn errors of metabolism are inherited disorders that present in early childhood and are usually caused by monogenic recessive mutations in specific enzymes that metabolize dietary components. Distinct mutations are present in specific populations. To determine which genomic variants are present in Pakistani cohorts with hepatorenal tyrosinemia type 1 (HT1) and fructose 1,6-bisphosphatase deficiency (FBPD).

Antifungals in a case of basidiobolomycosis: role and limitations.

A 10-year-old Saudi boy was diagnosed to have basidiobolomycosis after a stormy course of his ailment. Therapy was initiated with intravenous antifungal, voriconazole, which was well tolerated for 6 weeks except for local excoriation at the site of ileostomy. He developed drug-induced hepatitis on oral voriconazole, therefore, switched to oral itraconazole following which he experienced severe chest pain.

Unusual case of Juvenile Tay-Sachs disease.

Tay-Sachs disease (TSD) is a type 1 gangliosidosis (GM2) and caused by hexosaminidase A deficiency resulting in abnormal sphingolipid metabolism and deposition of precursors in different organs. It is a progressive neurodegenerative disorder transmitted in an autosomal-recessive manner. There is an accumulation of GM2 in neurocytes and retinal ganglions which result in progressive loss of neurological function and formation of the cherry-red spot which is the hallmark of TSD.

Minimally invasive autopsy for fetuses and children based on a combination of post-mortem MRI and endoscopic examination: a feasibility study.

Background: Less invasive perinatal and paediatric autopsy methods, such as imaging alongside targeted endoscopy and organ biopsy, may address declining consent rates for traditional autopsy, but their acceptability and accuracy are not known.

Objectives: The aims of this study were to provide empirical data on the acceptability and likely uptake for different types of autopsy among key stakeholders (study 1); and to analyse existing autopsy data sources to provide estimates of the potential efficacy of less invasive autopsy (LIA) and its projected utility in clinical practice (study 2).

Review Methods: Study 1: this was a mixed-methods study.

Leptin Is Not Essential for Obesity-Associated Hypertension.

Background And Objective: Hyperleptinemia is supposed to play a causal role in the development of obesity-associated hypertension, possibly via increased sympathetic tone. Hence patients with congenital leptin deficiency should be hypotensive and their low blood pressure should increase under leptin substitution.

Subjects And Methods: To test this assumption, we examined ambulatory blood pressure, resting heart rate, Schellong test results, cold pressor test results, heart rate variability, catecholamine metabolites, and aldosterone levels in 6 patients with congenital leptin deficiency before as well as 2-7 days and 7-14 months after the start of leptin substitution.

Bernard Soulier Syndrome: 10 years' experience at a tertiary care hospital.

Objective: To determine clinical manifestations and laboratory findings in patients with BSS diagnosed through platelet aggregometry followed in a tertiary care hospital in Lahore, Pakistan.

Methods: The retrospective study comprised patients who presented in Hematology and Transfusion Medicine Department of The Children Hospital & Institute of Child Health, Lahore with the relevant diagnosis from 2006 to 2013. The result of all the patients were collected on a predesigned proforma.

Shprintzen-Goldberg Syndrome: A Rare Disorder.

The Shprintzen-Goldberg syndrome (SGS) or velo-cardio-facial syndrome (VCFS) is an extremely rare disorder of connective tissue with a characteristic facial dysmorphism, marfanoid features, craniosynostosis, dolichocephaly, cardiovascular anomalies and mild to moderate mental retardation. It may be a de novo gene mutation or inherited as an autosomal dominant disorder having SKI gene and Fibrillin-1 gene (FBN1) mutations, located on chromosome 15q21.1.

Occupational health surveillance: pulmonary function testing and oxidative stress among photocopying workers in Pakistan.

Background: The photocopying occupation contributes to various health issues in workers. Elevated levels of oxidative stress have been found to be associated with respiratory problems in occupational workers. The intention of the current research is to evaluate the association between the pulmonary function parameters, a biomarker of oxidative stress, and the photocopying occupation in Lahore, Pakistan.

Pediatric Malignant Mediastinal Masses.

Objective: To describe the clinical spectrum and outcome-associated variables of pediatric malignant mediastinal masses in a resource-limited setting.

Study Design: Descriptive study.

Place And Duration Of Study: Department of Pediatric Hematology-Oncology, The Children's Hospital, Lahore, from October 2016 to November 2017.

Frequency of risk factors, vaccination status and outcome of tetanus in children at the Children's Hospital Lahore.

Objective: To determine the frequency of risk factors, vaccination status and outcome of tetanus in children beyond neonatal age at a tertiary care centre.

Methods: The prospective observational study was conducted at The Children's Hospital, Lahore, Pakistan, from January 2012 to December 2014, and comprised children aged between 1 month and 15 years of either gender admitted with diagnosis of tetanus. Variables recorded included age, gender, vaccination status in terms of number of diphtheria, tetanus and pertussis vaccine doses received per routine infant immunisation and booster doses of tetanus toxoid, risk factors as trauma, ear discharge, ear prick and duration of hospitalisation and outcome.

Phase I/II Trial of Liver-derived Mesenchymal Stem Cells in Pediatric Liver-based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients.

Background: Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases.

Objective: This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy.

Clinical, neuroradiological, and biochemical features of SLC35A2-CDG patients.

SLC35A2-CDG is caused by mutations in the X-linked SLC35A2 gene encoding the UDP-galactose transporter. SLC35A2 mutations lead to hypogalactosylation of N-glycans. SLC35A2-CDG is characterized by severe neurological symptoms and, in many patients, early-onset epileptic encephalopathy.