Insight into hypoglycemia frequency in congenital hyperinsulinism: evaluation of a large UK CGM dataset (original) (raw)
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Syndromic Forms of Hyperinsulinaemic Hypoglycaemia—A 15‐year follow‐up Study
Clinical Endocrinology, 2021
ObjectiveHyperinsulinaemic hypoglycaemia (HH) is one of the commonest causes of hypoglycaemia in children. The molecular basis includes defects in pathways that regulate insulin release. Syndromic conditions like Beckwith‐Wiedemann (BWS), Kabuki (KS) and Turner (TS) are known to be associated with a higher risk for HH. This systematic review of children with HH referred to a tertiary centre aims at estimating the frequency of a syndromic/multisystem condition to help address stratification of genetic analysis in infants with HH.MethodsWe performed a retrospective study of 69 patients with syndromic features and hypoglycaemia in a specialist centre from 2004 to 2018.ResultsBiochemical investigations confirmed HH in all the cases and several genetic diagnoses were established. Responsiveness to medications and the final outcome following medical treatment or surgery were studied.ConclusionsThis study highlights the association of HH with a wide spectrum of syndromic diagnoses and that...
Variation in Glycemic Outcomes in Focal Forms of Congenital Hyperinsulinism—The UK Perspective
Journal of the Endocrine Society, 2022
Context In focal congenital hyperinsulinism (CHI), localized clonal expansion of pancreatic β-cells causes excess insulin secretion and severe hypoglycemia. Surgery is curative, but not all lesions are amenable to surgery. Objective We describe surgical and nonsurgical outcomes of focal CHI in a national cohort. Methods Patients with focal CHI were retrospectively reviewed at 2 specialist centers, 2003-2018. Results Of 59 patients with focal CHI, 57 had heterozygous mutations in ABCC8/KCNJ11 (51 paternally inherited, 6 de novo). Fluorine-18 L-3,4 dihydroxyphenylalanine positron emission tomography computed tomography scan identified focal lesions in 51 patients. In 5 patients, imaging was inconclusive; the diagnosis was established by frozen section histopathology in 3 patients, a lesion was not identified in 1 patient, and 1 declined surgery. Most patients (n = 56) were unresponsive to diazoxide, of whom 33 were unresponsive or partially responsive to somatostatin receptor analog (...
Reviews in Endocrine and Metabolic Disorders, 2020
Hyperinsulinemic hypoglycemia (HH) is characterized by unregulated insulin release, leading to persistently low blood glucose concentrations with lack of alternative fuels, which increases the risk of neurological damage in these patients. It is the most common cause of persistent and recurrent hypoglycemia in the neonatal period. HH may be primary, Congenital HH (CHH), when it is associated with variants in a number of genes implicated in pancreatic development and function. Alterations in fifteen genes have been recognized to date, being some of the most recently identified mutations in genes HK1, PGM1, PMM2, CACNA1D, FOXA2 and EIF2S3. Alternatively, HH can be secondary when associated with syndromes, intra-uterine growth restriction, maternal diabetes, birth asphyxia, following gastrointestinal surgery, amongst other causes. CHH can be histologically characterized into three groups: diffuse, focal or atypical. Diffuse and focal forms can be determined by scanning using fluorine-1...
Heterogeneity of persistent hyperinsulinaemic hypoglycaemia. A series of 175 cases
European Journal of Pediatrics, 2002
Hyperinsulinism is a heterogeneous disorder characterised by severe hypoglycaemia due to an inappropriate oversecretion of insulin. In a personal series of 175 patients investigated for hyperinsulinaemic hypoglycaemia over the last 20 years, we review clinical presentations, molecular studies and therapeutic management of hyperinsulinism. There were 98 neonatal-onset patients, including 86 permanent hyperinsulinism and 12 transient forms, 68 with infancy-onset and nine with childhood-onset. Hyperammonaemia was found in 12 out of 69 patients tested, 4 neonates and 8 infants. Neonates were clinically more severely affected than infants. Diagnosis of infancy-onset hyperinsulinism was often delayed because of less profound hypoglycaemia and better tolerance to hypoglycaemia. Neonates required higher rates of iv glucose than infants to maintain normal plasma glucose levels (16 mg/kg per min versus 12 mg/kg per min). Only 16% of neonates were diazoxide-sensitive compared to 66% of the infants. Neonates with hyperammonaemia or transient hyperinsulinism were diazoxide-sensitive. Most neonates were pancreatectomised whereas 65% of the infants were treated medically. Among surgically-treated patients, 47% had a focal adenomatous hyperplasia (31 neonates and 13 infants) and 53% a diffuse form of hyperinsulinism (39 neonates and 11 infants). Diazoxide-responsiveness in the focal and diffuse forms did not differ in both neonates and infants; it depended only upon the age of onset of hypoglycaemia. One or two mutations, SUR1 or KIR6.2, were found in 41 of 73 neonates who were investigated and in 13/38 infants using polymerase chain reaction-single strand conformational polymorphism analysis of both genes. Almost all patients with SUR1 (38/41) or KIR6.2 (5/7) mutations were resistant to diazoxide. Ten patients with hyperinsulinism-hyperammonaemia syndrome had a mutation in the glutamate dehydrogenase gene (three neonates and seven infants) after reverse transcriptase-polymerase chain reaction and sequence analysis of cDNA. No mutation was found by polymerase chain reaction-single strand conformational polymorphism in the glucokinase gene. Eight of nine patients with childhood onset hyperinsulinism were treated surgically and histological examination confirmed an adenoma in each case. Conclusion: the clinical severity of hyperinsulinism varies mainly with age at onset of hypoglycaemia. The heterogeneity of hyperinsulinism has major consequences in terms of therapeutic outcome and genetic counselling.
Hyperinsulinemic Hypoglycemia in Infancy: Current Concepts in Diagnosis and Management
Indian pediatrics, 2015
Molecular basis of various forms of hyperinsulinemic hypoglycemia, involving defects in key genes regulating insulin secretion, are being increasingly reported. However, the management of medically unresponsive hyperinsulinism still remains a challenge as current facilities for genetic diagnosis and appropriate imaging are limited only to very few centers in the world. We aim to provide an overview of spectrum of clinical presentation, diagnosis and management of hyperinsulinism. We searched the Cochrane library, MEDLINE and EMBASE databases, and reference lists of identified studies. Analysis of blood samples, collected at the time of hypoglycemic episodes, for intermediary metabolites and hormones is critical for diagnosis and treatment. Increased awareness among clinicians about infants at-risk of hypoglycemia, and recent advances in genetic diagnosis have made remarkable contribution to the diagnosis and management of hyperinsulinism. Newer drugs like lanreotide a long acting so...
Congenital hyperinsulinism: management and outcome, a single tertiary centre experience
European Journal of Pediatrics, 2020
Hyperinsulinemic hypoglycaemia (HH) is the most frequent cause of persistent hypoglycaemia in neonates and infants. The most severe forms of HH are inherited and referred to as congenital hyperinsulinism (CHI). Diazoxide is the mainstay of treatment, with surgery being an option in appropriate cases. To describe the management and outcome of patients with CHI within our service. Children referred to or attending HH clinic between 2009 and 2017 were identified. Clinical course, genetics and interventions were documented. A total of 39 children were identified, and seven patients with secondary and syndromic HH were excluded. Most were born with an appropriate weight for gestational age (62.5%). Diazoxide was started in all patients; however, 7 did not respond and required octreotide/continuous feeding, with 6/7 requiring surgery. Genetic mutations were detected in 12/32 (37.5%). Hyperinsulinism resolved in conservatively treated patients within 12 months in 11/32 (34.3%) compared to 14/32 (43.7%) requiring more than 12 months of medication. A total of 7 patients underwent pancreatectomy. Conclusion: Although LGA and SGA are risk factors, most babies in our cohort are born AGA. A genetic mutation does not exclude medical remission; long-term conservative treatment of CHI is feasible as surgery does not guarantee complete remission. What is Known: •Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disorder that is the most common cause of permanent hypoglycaemia in infants and children. •Identification of genetic mutations and the use of 18F-DOPA PET scan when feasible lead to better outcomes. What is New: •The study describes clinical criteria, management and outcome of large number of patients with CHI in single tertiary centre. •Conservative treatment is feasible without the need for surgery, with HH resolving in over 30% within 12 months, irrespective of genetic mutation.
Current Status of Childhood Hyperinsulinaemic Hypoglycaemia in Turkey
Journal of Clinical Research in Pediatric Endocrinology, 2016
Congenital hyperinsulinism (CHI) is a rare disease characterized by dysregulated insulin secretion from pancreatic β-cells. Recurrent hypoglycemia can lead to neurological insult and permanent brain injury. Recently, there are important advances in understanding the genetic mechanisms, histological characteristics, imaging, and surgical techniques of congenital hyperinsulinemic hypoglycemia that could reflect to improvement in the clinical care of infants with this disorder. In Turkey, there is a high rate of consanguinity, thus, the incidence of CHI is expected to be high. Until now, there are no nationwide data regarding the disorder, and some individual case reports or case series had been published. Determining the characteristics of Turkish patients with CHI can help develop a different perspective on this rare disease. In this review, we evaluated the clinical and molecular characteristics of Turkish patients with CHI based on reports published in the literature. The most frequently seen mutations were ABCC8 gene mutations (n=37), followed by HADH (n=11) and KCNJ11 gene (n=7) mutations. A total of 141 Turkish patients with CHI were reported until now. Among them, 115 patients had been genetically analyzed, and 56 of them had one of the mutation leading to hyperinsulinism.
Italian Journal of Pediatrics
Background Congenital Hyperinsulinism typically occurs with a neonatal hypoglycemia but can appear even in childhood or in adolescence with different types of glucose metabolism derangements. Current diagnostic algorithms don’t take into account cases with a late presentation. Patients and methods Clinical and laboratory data of twenty-two subjects diagnosed at Federico II University of Naples have been described: patients have been divided according to the molecular defect into channel defects, metabolic defects and unidentified molecular defects. A particular focus has been made on three cases with a late presentation. Results and conclusions Late presentation cases may not be identified by previous diagnostic algorithms. Consequently, it seems appropriate to design a new flow-chart starting from the age of presentation, also considering that late presentation cases can show glucose metabolism derangements other than hypoglycaemic crises such as diabetes, glucose intolerance, post...
Effects of Hypoglycemia on Developmental Outcome in Children With Congenital Hyperinsulinism
Journal of Pediatric Nursing, 2005
Children with congenital hyperinsulinism are at risk for recurring, severe episodes of hypoglycemia that can cause seizures, brain damage, and developmental delay. To assess the frequency of permanent brain damage in this disorder, we carried out a telephone survey of 68 children who presented to The Children's Hospital of Philadelphia between 1980 and 2000. One third of the group had some degree of developmental delay. Those presenting in the first week of life and those with medically unresponsive hyperinsulinism were more likely to have delays. Early recognition and control of hypoglycemia are essential for preventing developmental delay in these children.