Renuka P Dias

• BMedSci MBBS PhD FRCPCH
• University of Birmingham

Introduction T1 Diabetes (T1D) is one of the most common chronic diseases in children and young people [1] with almost 34 000 aged 18 years or less living with T1D [2]. Physical activity is promoted as one of a number of management tools for people living with diabetes, being associated with significant health benefits including improved glycaemic...

Background WFS1 spectrum disorder, also known as Wolfram syndrome (WS) is an ultra‐rare (<1:500,000; ORPHA: 3463) monogenic (OMIM #222300) progressive neuroendocrine and neurodegenerative disorder, characterised by early‐onset insulin‐dependent diabetes, optic atrophy, central diabetes insipidus and sensi‐neuronal deafness. It is caused predominant...

Children and adolescents with type 1 diabetes mellitus (T1D) are less active than recommended and than their peers without T1D. Several barriers to physical activity have been reported, including lack of confidence in the support received from those who facilitate physical activity such as sports coaches and PE teachers (physical activity providers...

Introduction Wolfram syndrome (WFS1-Spectrum Disorder) is an ultra-rare monogenic form of progressive neurodegeneration and diabetes mellitus. In common with most rare diseases, there are no therapies to slow or stop disease progression. Sodium valproate, an anticonvulsant with neuroprotective properties, is anticipated to mediate its effect via al...

Aim The EarLy Surveillance for Autoimmune (ELSA) study aims to explore the feasibility and acceptability of UK paediatric general population screening for type 1 diabetes. Methods We aim to screen 20,000 children aged 3–13 years for islet‐specific autoantibodies through dried blood spot sample collection at home, hospital or community settings. Ch...

Aim: Type 1 diabetes (T1D) is one of the most common chronic conditions in children and adolescents. Approximately 1.5 million young people are currently living with T1D throughout the world. Despite recent improvement in overall indices of metabolic control in children and adolescents with T1D, control remains suboptimal and additional approaches...

Introduction We describe the identification and management of general population screen-detected type 1 diabetes (T1D) and share learnings for best practice. Research design and methods Children diagnosed with T1D through a general population screening initiative, the EarLy Surveillance for Autoimmune diabetes (ELSA) study, were reviewed and descr...

Objectives The EarLy Surveillance for Autoimmune Diabetes study (ELSA, www.elsadiabetes.nhs.uk) is exploring the feasibility and acceptability of screening children for pre- symptomatic type 1 diabetes (T1D). One route of participation is through a home testing kit which collects a dried blood spot (DBS) on a card for measurement of islet- specific...

Objectives The ELSA study is exploring the feasibility and acceptability of screening children in the general population aged 3–13 years for type 1 diabetes (T1D). Children detected with T1D through screening have lower rates of presenting in diabetic ketoacidosis (DKA)¹ and better glucose control than T1D diagnosed following the usual routes of cl...

OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (CUL7). Hypogonadism and hypospadias have been described in only a few males. We report a patient with CUL7 pathogenic variant who had bifid scrotum and perineal hypospadias at bi...

Introduction Manufacturer-supported didactic teaching programmes offer effective automated insulin delivery (AID) systems onboarding in children and young people (CYP) with type 1 diabetes (T1D). However, this approach has limited flexibility to accommodate the needs of families requiring additional support. Research design and methods Evaluate th...

Background PTEN is primarily known as a tumour suppressor gene. However, research describes higher rates of difficulties including intellectual disability and difficulties relating to autism spectrum conditions (ASCs) in people with germline PTEN mutations. Other psychological characteristics/experiences are less often reported and are explored in...

Introduction Language barriers can pose a significant hurdle to successfully educating children and young people with type 1 diabetes (CYPD) and their families, potentially influencing their glycaemic control. Methods Retrospective case-control study assessing HbA1c values at 0, 3, 6, 9, 12 and 18 months post-diagnosis in 41 CYPD requiring interpr...

Background: Children with pre-symptomatic type 1 diabetes can be identified through testing for circulating islet autoantibodies. Identifying children at risk reduces the rates of diabetic ketoacidosis at presentation and allows participation in clinical trials for type 1 diabetes prevention. Aim: The Early Surveillance for Autoimmune diabetes s...

Objectives Children with pre-symptomatic type 1 diabetes (T1D) can be identified through testing for circulating islet autoantibodies. Identifying children at risk reduces the rates of diabetic ketoacidosis at presentation and allows participation in clinical trials for T1D prevention.The EarLy Surveillance for Autoimmune diabetes (ELSA) study is e...

Background Many children and adolescents with Type 1 Diabetes Mellitus (T1DM) don’t meet the recommended levels of physical activity. Healthcare professionals (HCPs) have a key role in supporting and encouraging children and adolescents with T1DM to be physically active. This study aims to understand the perspectives of HCPs in relation to supporti...

Background: Although differentiated thyroid carcinoma (DTC) is the most frequent endocrine pediatric cancer, it is rare in childhood and adolescence. While tumor persistence and recurrence are not uncommon, mortality remains extremely low. Complications of treatment are however reported in up to 48% of the survivors. Due to the rarity of the diseas...

Objectives Primary hyperparathyroidism (PHPT), whilst common in elderly populations, is rare in adolescents. Hereditary cases make up less than 10% of patients with PH. We report two patients with CDC73 mutation presenting in early adolescence. Case presentation Case 1: A 14-year-old patient was referred from an adolescent mental health unit with...

At present no European recommendations for the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC) exist. Differences in clinical, molecular, and pathological characteristics between pediatric and adult DTC emphasize the need for specific recommendations for the pediatric population. An expert panel was instituted by...

Objectives: Compare the clinical and cost-effectiveness of an established face to face (F2F) structured education program to a new remote (VIRTUAL) program teaching dynamic glucose management (DynamicGM) to children and young people with type 1 diabetes (CYPD) using continuous glucose monitoring (CGM). To ascertain the most effective DynamicGM str...

Background The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could...

Background P hosphatase and ten sin homologue ( PTEN ) is a cancer suppressor gene. Constitutional mutations affecting this gene are associated with several conditions, collectively termed PTEN hamartoma tumour syndromes (PHTS). In addition to hamartomas, PTEN aberrations have been associated with a range of non-tumoural phenotypes such as macrocep...

Purpose Disruptions of genomic imprinting are associated with congenital imprinting disorders (CIDs) and other disease states, including cancer. CIDs are most often associated with altered methylation at imprinted differentially methylated regions (iDMRs). In some cases, multiple iDMRs are affected causing multilocus imprinting disturbances (MLIDs)...

Background Wolfram syndrome (WFS) is a rare disorder characterised by childhood-onset diabetes mellitus and progressive optic atrophy. Most patients have variants in the WFS1 gene. We undertook functional studies of WFS1 variants and correlated these with WFS1 protein expression and phenotype. Methods 9 patients with a clinical diagnosis of WFS we...

Objectives Create and evaluate the effectiveness of a structured education program in children and young people (CYP) with type 1 diabetes using continuous glucose monitoring (CGM). Design & Methods Step 1: CGM devices were evaluated for pre‐determined criteria using a composite score. Step 2: The education program was developed following review o...

Aims The UK newborn screening program facilitates early identification and treatment of Congenital Hypothyroidism (CHT) to prevent neurodevelopmental defects. This study audited practice and outcome data from a regional tertiary centre (RTC) over a 21 year period against the 2013 CHT national screening standards. Data from this centre was compared...

Objective: Androgen excess in childhood is a common presentation and may signify sinister underlying pathology. Data describing its patterns and severity are scarce, limiting the information available for clinical decision processes. Here, we examined the differential diagnostic value of serum dehydroepiandrosterone sulfate (DHEAS), androstenedione...

Type 1 diabetes mellitus is an autoimmune disorder characterized by the destruction of insulin‐secreting β cells, and subsequent insulin deficiency. Shortly after diagnosis, 60% of adults with Type 1 diabetes experience a period of partial remission, or ‘honeymoon’ period, characterized by low insulin requirement and good glycaemic control [1]. His...

Objective: To evaluate a novel approach to measure ß-cell function by frequent testing of C-peptide concentrations in 'dried blood spots' (DBS). Patients: Thirty-two children, aged 7-17 years, recently diagnosed with type 1 diabetes. Design: Mixed-meal-tolerance-test (MMTT) within 6 and again 12 months after diagnosis with paired venous and DB...

Background: Patients with homozygous intronic pseudoexon GH receptor(GHR) mutations(6Ψ) have growth hormone Insensitivity(GHI) (growth failure, IGF1 deficiency and normal/elevated serum GH). We report 9 patients in addition to previously described 11 GHR 6Ψ patients and their responses to rhIGF1 therapy. Methods: 20 patients (12 males, 11 famili...

Aim Wolfram syndrome is a rare genetic defect in WFS1 or WSF2(CISD2). It includes diabetes mellitus and insipidis, sensorineural deafness, optic atrophy, but not bladder dysfunction. However, this has appeared a common finding in our national referral clinic, and we sought to quantify this problem. Methods Data were collected from a multidisciplin...

Supp. Table S1 Patients included in the genotype‐phenotype analysis.

We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1,...

Objectives: Many successful European centres provide intensive education as 2 week inpatient admissions for newly diagnosed type 1 diabetes. Prolonged inpatient stay is resource intensive and disrupts the family unit. Our centre aimed to determine the feasibility of delivering an intensive education programme in an ambulatory care setting. Methods:...

This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver-Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However,...

Context: Steroid sulfatase (STS) cleaves the sulfate moiety off steroid sulfates, including DHEAS, the inactive sulfate ester of the adrenal androgen precursor DHEA. Deficient DHEA sulfation, the opposite enzymatic reaction to that catalyzed by STS, results in androgen excess by increased conversion of DHEA to active androgens. STS deficiency (STS...

Wolcott-Rallison Syndrome is the commonest cause of neonatal diabetes in consanguineous families. It is associated with liver dysfunction, epiphyseal dysplasia, and developmental delay. It is caused by mutations in eukaryotic translation initiation factor 2-α kinase 3 (EIF2AK3). We report 4 children with WRS and Os Odontoideum resulting in signific...

Background: Wolfram syndrome (WS) is a rare autosomal recessive disorder, characterised by early-onset diabetes and optic atrophy. It is caused by mutations in WFS1. Objective and hypotheses: This study aimed to comprehensively review the natural history of WS in a large cohort of patients from the EURO-WABB registry. Method: Data from EURO-WABB pa...

Background Beckwith-Wiedemann syndrome (BWS), a congenital overgrowth disorder with variable expressivity and a predisposition to tumorigenesis, results from disordered expression and/or function of imprinted genes at chromosome 11p15.5. There are no generally agreed clinical diagnostic criteria, with molecular studies commonly performed to confirm...

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder associated with abnormalities in 11p15.5 imprinted genes. The most common cause is loss of methylation (epimutation) at the imprinting control centre 2 (IC2/KvDMR1). Most IC2 epimutations occur sporadically but an association with conception after assisted reproductive technologi...

About half of all children with a clinical diagnosis of Silver-Russell syndrome (SRS) have a detectable molecular genetic abnormality (maternal uniparental disomy of chromosome upd(7)mat or hypomethylation of H19 differentially methylated region (DMR). The selection of children for molecular genetic testing can be difficult for non-specialists beca...

Genomic imprinting is a parent-of-origin allele-specific epigenetic process that is critical for normal development and health. The establishment and maintenance of normal imprinting is dependent on both cis-acting imprinting control centers, which are marked by differentially (parental allele specific) methylated marks, and trans mechanisms, which...

AimsWe prospectively evaluated the effect of insulin intensification on glycaemic control and lipid levels in children and young persons with Type 1 diabetes in relation to ethnicity.Methods In the first 2 years of a 3-year observation period, as part of routine clinical care, 231 children and young persons (40% white, 28% South Asian, 32% black) f...

Background: Silver-Russell syndrome (SRS; online inheritance in man 180860) is a low-birth-weight syndrome characterized by postnatal growth restriction and variable dysmorphic features. Although maternal uniparental disomy (UPD) of chromosome 7 and hypomethylation of H19 have been reported in up to 50% of all cases, no unifying mechanism is appar...

Missense mutations in the imprinted gene that encodes cyclin-dependent kinase inhibitor 1C (CDKN1C, also called p57Kip2) result in a rare disorder associated with prenatal growth retardation (IMAGe syndrome). Loss-of-function mutations in CDKN1C have been previously described in the congenital overgrowth syndrome Beckwith-Wiedemann syndrome and som...

Cushing’s syndrome (CS) is a rare pediatric problem on which few pediatric endocrinologists have extensive experience. Hence, close collaboration with an adult endocrinologist colleague is strongly recommended. This chapter reviews the main types of CS occurring in the pediatric age range. Results are presented from the authors’own experience of ma...

Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating germline protein kinase A regulatory subunit type 1-alpha (PRKAR1A) mutations and loss of heterozygosity at the 17q22-24 locus in approximately 50% patients. PRKAR1A mutations are observed in both isolated PPNAD (iPPNAD) and Carney complex (CNC). Most mutations...

Cushing's disease (CD) is rare in the paediatric age range, but presents a diagnostic and therapeutic challenge. Most paediatric endocrinologists have limited experience managing children or adolescents with CD and thus benefit from close consultation with adult colleagues. A diagnostic protocol for investigation is required which broadly follows t...

Cushing's disease (CD) in prepubertal children is very rare and presents important diagnostic and therapeutic challenges. We report experience of the management of this subpopulation of CD patients. Retrospective patient case note review. Between 1985 and 2008, 17 prepubertal children (13M, 4F), aged 5.7-14.1 years presented to our centre for diagn...

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease caused by ACTH resistance and leads to isolated glucocorticoid deficiency. Although FGD patients typically have normal mineralocorticoid secretion, subtle alterations in the renin-angiotensin-aldosterone axis have been reported in a subset of patients at presentation. An...