Publications by authors named "Shubha Srinivasan"

Aim: Abnormal thyroid function tests (TFTs) are found in a wide range of settings in hospitalised infants. This retrospective descriptive study reviewed management decisions and outcomes of these infants, identifying factors influencing clinicians' decision to treat with thyroxine.

Methods: Data were collected for all infants referred to the on-call endocrinology service at a tertiary Australian centre for thyroid dysfunction between 1 July 2019 and 30 June 2021.

View Article and Find Full Text PDF

Objectives: Clinical benefits of growth hormone (GH) in Prader-Willi syndrome (PWS) are proven and scoliosis is a known association of both PWS and GH therapy. The aims of this study were to assess GH prescribing practices and growth outcomes over time, the prevalence and predictors of scoliosis in GH-treated PWS children, and the near-final height of GH-treated PWS patients.

Design And Methods: This is a retrospective, descriptive study evaluating data from all clinic visits of patients aged 0-18 years with PWS, seen through the Children's Hospital at Westmead between March 1992 and May 2022 (n=75).

View Article and Find Full Text PDF

Introduction: Familial hypercholesterolaemia (FH) is an autosomal dominant inherited disorder of lipid metabolism and a preventable cause of premature cardiovascular disease. Current detection rates for this highly treatable condition are low. Early detection and management of FH can significantly reduce cardiac morbidity and mortality.

View Article and Find Full Text PDF

Despite the availability of life-saving corticosteroids for 70 years, treatment for adrenal insufficiency is not able to recapitulate physiological diurnal cortisol secretion and results in numerous complications. Gene therapy is an attractive possibility for monogenic adrenocortical disorders such as congenital adrenal hyperplasia; however, requires further development of gene transfer/editing technologies and knowledge of the target progenitor cell populations. Vectors based on adeno-associated virus are the leading system for direct gene delivery but have limitations in targeting replicating cell populations such as in the adrenal cortex.

View Article and Find Full Text PDF

Background And Aims: Homozygous familial hypercholesterolaemia (FH) causes severe cardiovascular disease from childhood. Conventional drug therapy is usually ineffective; lipoprotein apheresis (LA) is often required. Liver transplantation (LT) can correct the metabolic defect but is considered a treatment of last resort.

View Article and Find Full Text PDF

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels due to profoundly defective LDL receptor (LDLR) function. Given that severely elevated LDL-C starts in utero, atherosclerosis often presents during childhood or adolescence, creating a largely unmet need for aggressive LDLR-independent lipid-lowering therapies in young patients with HoFH. Here we present the first evaluation of the efficacy and safety of evinacumab, a novel LDLR-independent lipid-lowering therapy, in pediatric patients with HoFH from parts A and B of a 3-part study.

View Article and Find Full Text PDF

Objectives: Genotype-phenotype correlation in congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency ranges from 45 to 97 %. We performed massively parallel sequencing of on stored newborn bloodspot samples to catalogue the genotypes present in our patients with CAH and enable genotype-phenotype comparison.

Methods: Participants ≤15 years old with clinically diagnosed CAH were recruited from The Sydney Children's Hospitals Network.

View Article and Find Full Text PDF

The clinical outcome for children and adolescents with homozygous familial hypercholesterolaemia (HoFH) can be devastating, and treatment options are limited in the presence of a null variant. In HoFH, atherosclerotic risk accumulates from birth. Gene therapy is an appealing treatment option as restoration of low-density lipoprotein receptor (LDLR) gene function could provide a cure for HoFH.

View Article and Find Full Text PDF
Article Synopsis
  • * In Australia and New Zealand, an estimated 22,000 children and teens have FH, yet many go unnoticed until later in life or after heart problems arise.
  • * The paper aims to boost awareness and provide practical guidelines for diagnosing and managing FH in young people, including the use of treatments and genetic testing, while emphasizing the need for targeted detection and tailored care models to improve health outcomes.
View Article and Find Full Text PDF
Article Synopsis
  • The text mentions a correction to a previously published article with the DOI: 10.1016/j.ajpc.2021.100151.
  • This correction suggests that there were errors or inaccuracies in the original article that needed to be addressed.
  • The updated information is important for researchers and readers who rely on the findings of that specific study.
View Article and Find Full Text PDF

Introduction: Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease, with significant potential for positive impact on public health and healthcare savings. New clinical practice recommendations are presented in an abridged guidance to assist practitioners in enhancing the care of all patients with FH.

Main Recommendations: Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH.

View Article and Find Full Text PDF

Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease. New clinical practice recommendations are presented to assist practitioners in enhancing the care of all patients with FH. Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH.

View Article and Find Full Text PDF

Aim: Management of children with differences/disorders of sex development (DSD) is complex with limited evidence to guide clinical decisions. Regular multidisciplinary team meetings were set up in Sydney and Melbourne paediatric hospitals to enable systematic peer review of complex decision-making. We aim to describe the workload and role of these meetings.

View Article and Find Full Text PDF

Aim: To review the experience of a dedicated paediatric multidisciplinary lipid clinic in the management of familial hypercholesterolaemia (FH) by studying the demographics, clinical presentations as well as statin therapy and outcomes.

Methods: Retrospective database review of all patients under 18 years old seen in the lipid clinic at an Australian tertiary paediatric hospital between April 1999 and August 2017. Outcome measures collected included patient demographics, family history, lipid profile, age at treatment commencement, treatment outcomes and complications.

View Article and Find Full Text PDF

Aim: Paediatric hypoglycaemia often requires specific investigations to determine aetiology. Samples from the time of hypoglycaemia may not be available and a diagnostic fasting test may be required. Additionally, fasting studies can determine safe fasting intervals and prolonged oral glucose challenges can assess hypoglycaemia due to abnormal post-prandial glucose handling.

View Article and Find Full Text PDF

Familial hypercholesterolaemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). There are approximately 100,000 people with FH in Australia. However, an overwhelming majority of those affected remain undetected and inadequately treated, consistent with FH being a leading challenge for public health genomics.

View Article and Find Full Text PDF

In Australia, all newborns born in New South Wales (NSW) and the Australia Capital Territory (ACT) have been offered screening for rare congenital conditions through the NSW Newborn Screening Programme since 1964. Following the development of the Australian Newborn Bloodspot Screening National Policy Framework, screening for congenital adrenal hyperplasia (CAH) was included in May 2018. As part of the assessment for addition of CAH, the national working group recommended a two-tier screening protocol determining 17α-hydroxyprogesterone (17OHP) concentration by immunoassay followed by steroid profile.

View Article and Find Full Text PDF

Background: Differences/disorders of sex development (DSD) or 'intersex' encompass a broad range of congenital variations in the complex pathways involved in the development of sex characteristics. Components of these pathways include sex chromosomes, genes involved in gonadal development, hormone production and action, and the development of internal and external genital structures. Many variations are rare, and some (eg congenital adrenal hyperplasia) are associated with urgent medical needs.

View Article and Find Full Text PDF

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously.

View Article and Find Full Text PDF

Many years after first being described, there is still no clear consensus on diagnostic criteria for metabolic syndrome, particularly in children. However, identification of this cluster of cardiovascular risk factors especially in children with co-morbidities, is important in order to reduce their future risk of chronic disease and morbidity. Sustained multidisciplinary and family-based early intervention is required, aiming primarily at life-style change.

View Article and Find Full Text PDF

Background: A higher protein to carbohydrate ratio in the diet may potentiate weight loss, improve body composition and cardiometabolic risk, including glucose homeostasis in adults. The aim of this randomised control trial was to determine the efficacy of two structured lifestyle interventions, differing in dietary macronutrient content, on insulin sensitivity and body composition in adolescents. We hypothesised that a moderate-carbohydrate (40-45% of energy), increased-protein (25-30%) diet would be more effective than a high-carbohydrate diet (55-60%), moderate-protein (15%) diet in improving outcomes in obese, insulin resistant adolescents.

View Article and Find Full Text PDF

Rates of type 1 diabetes are rising globally, with a decreasing proportion of high-risk genotypes and twin concordance rates below 50%. Therefore, environmental factors such as viruses, nutrition and overweight have been examined as putative aetiological agents. The accelerator hypothesis proposes that overweight and insulin resistance are central to both type 1 and type 2 diabetes and may explain, in part, the rise in type 1 diabetes incidence.

View Article and Find Full Text PDF

Objective: To examine the association between glycaemic control, insulin resistance and hyperandrogenism on cardiac autonomic function in peripubertal girls with type 1 diabetes.

Design: Prospective, clinic-based study of 125 girls with diabetes and 46 age-matched nondiabetic girls.

Measurements: Heart rate variability (HRV) parameters derived from a 10-min ECG recording using LabChart Pro were as follows: standard deviation of mean NN intervals (SDNN), where NN = adjacent QRS complexes; root mean squared difference of successive NN intervals (RMSSD) - estimates of overall HRV; and low-/high-frequency (LF:HF) ratio - an estimate of the sympathovagal balance.

View Article and Find Full Text PDF

Context: Prediabetes and clinical insulin resistance in adolescents are rapidly emerging clinical problems with serious health outcomes.

Objective: The objective of this study was to determine the efficacy of 2 structured lifestyle interventions, both differing in diet macronutrient composition, on insulin sensitivity.

Design: This study was a randomized controlled trial, known as Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers, in 2 hospitals in Sydney, Australia.

View Article and Find Full Text PDF