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K Hussain - One of the best experts on this subject based on the ideXlab platform.
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Congenital Hyperinsulinism (CHI)
Advanced Practice in Endocrinology Nursing, 2019Co-Authors: Claire Gilbert, Kate Morgan, Louise Doodson, K HussainAbstract:The aim of this chapter is to highlight a rare endocrine condition (Congenital Hyperinsulinism, CHI), which can cause low blood glucose levels leading to permanent brain injury. Many Paediatric Nurses are unfamiliar with this condition. CHI is caused by unregulated insulin secretion from the pancreas and typically presents in the newborn period, but it can also present later in life. It is imperative for Paediatric Nurses to be knowledgeable on the subject of CHI as they are usually the first to identify the infant’s low blood glucose levels, often accompanied by non-specific symptoms such as floppiness, jitteriness, fitting, lethargy, or poor feeding. It is always important to consider CHI if an infant or child presents with unexplained recurrent and persistent hypoglycaemia.
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Molecular mechanisms of Congenital Hyperinsulinism
Journal of molecular endocrinology, 2015Co-Authors: Sofia Rahman, Azizun Nessa, K HussainAbstract:Congenital Hyperinsulinism (CHI) is a complex heterogeneous condition in which insulin secretion from pancreatic β-cells is unregulated and inappropriate for the level of blood glucose. The inappropriate insulin secretion drives glucose into the insulin-sensitive tissues, such as the muscle, liver and adipose tissue, leading to severe hyperinsulinaemic hypoglycaemia (HH). At a molecular level, genetic abnormalities in nine different genes (ABCC8, KCNJ11, GLUD1, GCK, HNF4A, HNF1A, SLC16A1, UCP2 and HADH) have been identified which cause CHI. Autosomal recessive and dominant mutations in ABCC8/KCNJ11 are the commonest cause of medically unresponsive CHI. Mutations in GLUD1 and HADH lead to leucine-induced HH, and these two genes encode the key enzymes glutamate dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase which play a key role in amino acid and fatty acid regulation of insulin secretion respectively. Genetic abnormalities in HNF4A and HNF1A lead to a dual phenotype of HH in the newborn period and maturity onset-diabetes later in life. This state of the art review provides an update on the molecular basis of CHI.
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Congenital Hyperinsulinism in a newborn with a novel homozygous mutation (p.Q392H) in the ABCC8 gene.
Journal of pediatric endocrinology & metabolism : JPEM, 2014Co-Authors: Deniz Anuk Ince, K Hussain, Sarah E. Flanagan, Nursel Muratoglu Sahin, Ayşe Ecevit, Abdullah Kurt, Sibel Tulgar Kinik, Aylin TarcanAbstract:Congenital Hyperinsulinism is the most frequent cause of persistent hypoglycemia in infancy. We present the case of a preterm, large-for-gestation-age infant with Congenital Hyperinsulinism who was found to have a novel p.Q392H homozygous mutation in the ABCC8 gene. The patient had severe brain damage, despite early diagnosis and appropriate management. The new mutations may provide an understanding of the prognosis and treatment of the disease. In addition, the data will help the family make informed decisions about future pregnancies.
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Short term outcome of Congenital Hyperinsulinism: case series
International Journal of Pediatric Endocrinology, 2013Co-Authors: Song Hai Lim, Sian Ellard, Janet Yh Hong, Sarah Flanagan, K HussainAbstract:Congenital Hyperinsulinism (CH) is a major cause of recurrent hypoglycaemia in neonates and infants, results in varying degrees of neurological impairment. Advances in molecular study and imaging technique have been used to guide treatment option for CH. However, there were centres treating CH with long-term medications and reported good neurodevelopmental outcome.
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Congenital Hyperinsulinism presenting with different clinical, biochemical and molecular genetic spectra.
The Turkish journal of pediatrics, 2013Co-Authors: Sarah E. Flanagan, Sian Ellard, K HussainAbstract:Congenital Hyperinsulinism (CHI) is a common cause of hypoglycemia in infants. We report three cases of CHI with differing clinical, biochemical, and molecular genetic spectra. One patient was unresponsive to medical treatment and died after subtotal pancreatectomy because of complications due to the surgery. Two patients have been followed successfully with medical treatment. Early diagnosis and appropriate treatment of CHI are essential to prevent morbidity and mortality.
Charles A. Stanley - One of the best experts on this subject based on the ideXlab platform.
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accuracy of pet ct scan in the diagnosis of the focal form of Congenital Hyperinsulinism
Journal of Pediatric Surgery, 2013Co-Authors: Pablo Laje, Andrew A. Palladino, Charles A. Stanley, Lisa J. States, Hongming Zhuang, Susan Becker, Scott N AdzickAbstract:Purpose The purpose of the study was to determine the sensitivity of the 18fluoro-dihydroxyphenylalanine positron emission tomography/computed tomography scan (18 F-PET/CT) in the diagnosis of focal Congenital Hyperinsulinism (HI).
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Accuracy of PET/CT Scan in the diagnosis of the focal form of Congenital Hyperinsulinism
Journal of pediatric surgery, 2013Co-Authors: Pablo Laje, Andrew A. Palladino, Charles A. Stanley, Susan A. Becker, Lisa J. States, Hongming Zhuang, N. Scott AdzickAbstract:Purpose The purpose of the study was to determine the sensitivity of the 18fluoro-dihydroxyphenylalanine positron emission tomography/computed tomography scan (18 F-PET/CT) in the diagnosis of focal Congenital Hyperinsulinism (HI).
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Historical Perspective on the Genetic Forms of Congenital Hyperinsulinism
Monogenic Hyperinsulinemic Hypoglycemia Disorders, 2012Co-Authors: Charles A. Stanley, Franz M. MatschinskyAbstract:Since 1995, a total of 8 genetic defects in the pathways of beta- cell insulin secretion have been identified that cause Congenital Hyperinsulinism. These advances parallel the discovery of 10 different monogenic diabetes disorders. Together these disorders of islet regulation provide important insight into the mechanisms controlling beta- cell insulin secretion not only in patients, but also in normal humans.
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Rare forms of Congenital Hyperinsulinism
Seminars in pediatric surgery, 2011Co-Authors: Jan Marquard, Andrew A. Palladino, Charles A. Stanley, Ertan Mayatepek, Thomas MeissnerAbstract:Rare forms of Congenital Hyperinsulinism (CHI) are caused by mutations in GLUD1 (encoding glutamate dehydrogenase), GCK (encoding glucokinase), HADH (encoding for L-3-hydroxyacyl-CoA dehydrogenase), SLC16A1 (encoding the monocarboxylat transporter 1), HNF4A (encoding hepatocyte nuclear factor 4α) or UCP2 (encoding mitochondrial uncoupling protein 2). The clinical presentation is very heterogeneous in regards to age of onset, severity, and manner of symptoms, as well as the response to medical treatment. Special individual characteristics have to be accounted in diagnosis and treatment. Diazoxide is the first-line drug for the rare forms of CHI for long-term treatment but is not entirely effective in some of these rarer defects (GCK, MCT1). The use of diazoxide is often limited by side effects and the use of octreotide as second-line drug has to be considered. A near-total pancreatectomy is only reserved for patients with diffuse disease and resistance to medical treatment as a last resort. Patients with CHI should be managed by centers with a highly experienced team in diagnostic work-up and treatment of this disease.
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Necrotizing enterocolitis in neonates receiving octreotide for the management of Congenital Hyperinsulinism.
Pediatric diabetes, 2009Co-Authors: Pablo Laje, N. Scott Adzick, Lori P. Halaby, Charles A. StanleyAbstract:Laje P, Halaby L, Adzick NS, Stanley CA. Necrotizing enterocolitis in neonates receiving octreotide for the management of Congenital Hyperinsulinism. The somatostatin analog octreotide was used for the first time in the treatment of an infant with Congenital Hyperinsulinism in 1986. Since then, it is commonly used in the management of Congenital hyperinsulinemic hypoglycemias. Despite a wide variety of potential adverse reactions, octreotide is generally well tolerated. It has been extensively demonstrated that octreotide reduces the splanchnic blood flow in a dose-dependent manner, affecting the entire gastrointestinal tract, and some concern has been recently raised regarding the potential implications of this effect in the development of necrotizing enterocolitis in neonates receiving octreotide for the management of Congenital Hyperinsulinism. The aim of this report is to present a series of patients treated at our institution in which we observed this association, and review the current related literature.
N. Scott Adzick - One of the best experts on this subject based on the ideXlab platform.
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Surgical treatment of Congenital Hyperinsulinism.
Seminars in pediatric surgery, 2020Co-Authors: N. Scott AdzickAbstract:A multidisciplinary approach to patients with Congenital Hyperinsulinism (HI) can distinguish focal from diffuse HI, localize focal lesions, and permit partial pancreatectomy with cure in almost all focal patients. Surgery does not cure diffuse disease but can help prevent severe hypoglycemia and brain damage. Surgery can be curative for insulinoma and for some cases of atypical HI.
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Surgery for Congenital Hyperinsulinism
2018Co-Authors: N. Scott Adzick, Pablo LajeAbstract:Transient hypoglycemia in the newborn period is common and generally associated either with immaturity of the glucose regulatory pathways (which responds to frequent feeds and resolves spontaneously within hours), or with stress-associated Hyperinsulinism (which responds well to hyperglycemic drugs and resolves spontaneously within the first few weeks or months of life). Congenital Hyperinsulinism (HI) is the most frequent cause of persistent, long-term hypoglycemia in newborns and infants, and can lead to severe and irreversible brain damage and developmental delay. It is a rare Congenital disorder of the glucose metabolism that has an estimated incidence of 1–1.4 cases per 50,000 live births, leading to about 80–120 new cases in the United States each year. An incidence as high as 1 in 2500 live births has been reported in populations with high consanguinity like Arabians and Ashkenazi Jews. Inappropriate oversecretion of insulin is the hallmark of HI, and the genetic background is quite variable. Depending on the genetic mutation, babies with HI may be treated medically or may require surgery either as a palliative treatment or as a definitive cure.
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Iatrogenic Necrolytic Migratory Erythema in an Infant with Congenital Hyperinsulinism.
Pediatric dermatology, 2015Co-Authors: Carrie C. Coughlin, N. Scott Adzick, Sani M. Roy, Lisa M. Arkin, Albert C. Yan, M.s.c.e. Diva D. De León, Adam I. RubinAbstract:Necrolytic migratory erythema (NME) is a rare cutaneous finding characterized by painful, pruritic, scaly red patches and plaques, bullae, and superficial erosions. Typically NME is a paraneoplastic phenomenon associated with glucagonoma. We report the exceptional case of an infant who developed iatrogenic NME arising secondary to glucagon therapy for Congenital Hyperinsulinism.
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Accuracy of PET/CT Scan in the diagnosis of the focal form of Congenital Hyperinsulinism
Journal of pediatric surgery, 2013Co-Authors: Pablo Laje, Andrew A. Palladino, Charles A. Stanley, Susan A. Becker, Lisa J. States, Hongming Zhuang, N. Scott AdzickAbstract:Purpose The purpose of the study was to determine the sensitivity of the 18fluoro-dihydroxyphenylalanine positron emission tomography/computed tomography scan (18 F-PET/CT) in the diagnosis of focal Congenital Hyperinsulinism (HI).
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Localization of a Focal Lesion of Congenital Hyperinsulinism: Imaging and Surgery
Monogenic Hyperinsulinemic Hypoglycemia Disorders, 2012Co-Authors: Lisa J. States, N. Scott AdzickAbstract:Approximately half of the infants with Congenital Hyperinsulinism who require surgical pancreatectomy for glucose control have a potentially curable focal lesion. Molecular imaging with [18
Raja Padidela - One of the best experts on this subject based on the ideXlab platform.
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Increased plasma incretin concentrations identifies a subset of patients with persistent Congenital Hyperinsulinism without KATP channel gene defects.
The Journal of pediatrics, 2014Co-Authors: Yanqin Shi, Jacques Rahier, Sarah E. Flanagan, Sian Ellard, Raja Padidela, Hima Bindu Avatapalle, Mars Skae, Melanie Newbould, Lindsey Rigby, Peter E. ClaytonAbstract:Congenital Hyperinsulinism causes profound hypoglycemia, which may persist or resolve spontaneously. Among 13 children with Congenital Hyperinsulinism, elevated incretin hormone concentrations were detected in 2 with atypical, persistent disease. We suggest that incretin biomarkers may identify these patients, and that elevated hormone levels may contribute to their pathophysiology.
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Can network biology unravel the aetiology of Congenital Hyperinsulinism
Orphanet journal of rare diseases, 2013Co-Authors: Adam Stevens, Indraneel Banerjee, Karen E. Cosgrove, Raja Padidela, Mars Skae, Peter E. Clayton, Mark J. DunneAbstract:Congenital Hyperinsulinism is a condition with a number of genetic causes, but for the majority of patients, the underlying aetiology is unknown. We present here a rational argument for the use of computational biology as a valuable resource for identifying new candidate genes which may cause disease and for understanding the complex mechanisms which define the pathophysiology of this rare disease.
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Focal Congenital Hyperinsulinism in a patient with septo-optic dysplasia
Nature Reviews Endocrinology, 2010Co-Authors: Raja Padidela, Clare Gilbert, Sarah E. Flanagan, Sian Ellard, Ritika R Kapoor, Yuva Moyo, K HussainAbstract:Background . An infant diagnosed as having hypopituitarism and on adequate hydrocortisone replacement therapy was referred to a tertiary endocrine unit at 5 weeks of age with persistent hypoglycemia that required a high rate of intravenous glucose infusion (up to 18 mg/kg•min^−1) to maintain euglycemia. Investigations . A controlled hypoglycemia screen was performed to measure levels of plasma glucose, insulin, C-peptide and 3-β-hydroxybutyrate concentrations. The pancreas was analyzed by fluorine-18- L -3,4-dihydroxyphenylalanine (^18F-DOPA) PET scan. Genetic analyses were performed on the peripheral blood leukocytes, and loss of heterozygosity within the resected focal lesion of the pancreas was investigated by microsatellite analysis. A glucagon stimulation test helped determine pituitary function, and an MRI of the brain and pituitary gland was performed to define the anatomy of the intracranial structures and the pituitary gland. Diagnosis . Focal form of Congenital Hyperinsulinism localized to the head of the pancreas, septo-optic dysplasia and pituitary hormone deficiencies. Management . Resection of the focal lesion from the head of the pancreas and hormonal replacement therapy for hypopituitarism. This Case Study describes an infant diagnosed as having focal Congenital Hyperinsulinism associated with septo-optic dysplasia, highlighting the importance of maintaining a high degree of suspicion in all infants who are investigated for chronic hypoglycemia. The authors report an as yet unidentified genetic etiology that may account for both focal Congenital Hyperinsulinism and septo-optic dysplasia.
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Focal Congenital Hyperinsulinism in a patient with septo-optic dysplasia
Nature reviews. Endocrinology, 2010Co-Authors: Raja Padidela, Clare Gilbert, Sarah E. Flanagan, Sian Ellard, Ritika R Kapoor, Yuva Moyo, K HussainAbstract:This Case Study describes an infant diagnosed as having focal Congenital Hyperinsulinism associated with septo-optic dysplasia, highlighting the importance of maintaining a high degree of suspicion in all infants who are investigated for chronic hypoglycemia. The authors report an as yet unidentified genetic etiology that may account for both focal Congenital Hyperinsulinism and septo-optic dysplasia.
Sarah E. Flanagan - One of the best experts on this subject based on the ideXlab platform.
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Focal Congenital Hyperinsulinism as a Cause for Sudden Infant Death.
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society, 2018Co-Authors: Amish Chinoy, Indraneel Banerjee, Mark J. Dunne, Sarah E. Flanagan, Sian Ellard, Bing Han, Zainab Mohamed, Stefania BitettiAbstract:Congenital Hyperinsulinism (CHI) is the commonest cause of persistent and severe hypoglycemia in infancy due to unregulated insulin secretion from pancreatic β-cells. Prompt early diagnosis is impo...
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Congenital Hyperinsulinism: A Novel Mutation in the KCNJ11 Gene
Journal of the Pancreas, 2017Co-Authors: Keziban Asli Bala, Nihat Demir, Oğuz Tuncer, Selami Kocaman, Sarah E. FlanaganAbstract:Introduction Hyperinsulinism is the most common cause of both transient and persistent hypoglycemia in the neonatal period. Hyperinsulinism due to mutations in the ATP-sensitive potassium channel encoded by the KCNJ11 and ABCC8 genes cause the most common and severe form of Hyperinsulinism. Herein, we present a case of Congenital Hyperinsulinism in which a novel KCNJ11 mutation was identified. Case Report An eight-day-old boy with a birth weight of 4,550 g born to a 32-year-old female with diabetes mellitus was transferred to our clinic with the diagnoses of respiratory distress syndrome, Congenital heart disease and hypoglycemia. A diagnosis of Congenital Hyperinsulinism was made based on the presence of elevated serum insulin levels (109 μIU/mL [2.6-24]) during hypoglycemia. Levels of serum growth hormone, cortisol, ammonium, and lactate were normal. Metabolic screening tests for blood and urine ketones and fatty acid oxidation defects were found to be normal. Glucose infusion (14 mg/kg/min), glucagon infusion, and diazoxide were initiated based on the diagnosis of hyperinsulinemic hypoglycemia; however, glycemic control was only achieved after the addition of octreotide and nifedipine. There were no abnormal findings in sonography and abdominal magnetic resonance imaging (MRI). Molecular diagnosis ABCC8 and KCNJ11 mutation analyses was performed on the genomic DNA extracted from peripheral blood. A novel homozygous missense mutation (p.E126K) was detected in KCNJ11 confirming the diagnosis of Congenital Hyperinsulinism. Conclusion A novel homozygous missense mutation (p.E126K) was detected in our case, which resulted in Hyperinsulinism.
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Molecular genetics, correlation between genotype and phenotype of 65 Vietnames patients with Congenital Hyperinsulinism
International Journal of Pediatric Endocrinology, 2015Co-Authors: Dang Anh Duong, Sarah E. Flanagan, Vu Chi Dung, Nguyen Phu Dat, Bui Phuong Thao, Can Thi Bich Ngoc, Nguyen Ngoc Khanh, Tran Minh Dien, Nguyen Thanh Liem, Sian EllardAbstract:Hyperinsulinemic hypoglycemia (HH) is a consequence of unregulated insulin secretion by pancreatic β-cells. Congenital HH is caused by mutations in genes involved in regulation of insulin secretion (ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1, HNF4A and UCP2). Severe forms of Congenital HH are caused by inactivating mutations in ABCC8 and KCNJ11, which encode the two components of the pancreatic β-cell ATP-sensitive potassium channel. Our aim is to identify mutations in the ABCC8 and KCNJ11, HNF4A and GLUD genes, and to describe genotype and phenotype correlations of Vietnamese children with Congenital Hyperinsulinism. A prospective study was conducted on 65 cases with Congenital Hyperinsulinism diagnosed and treated at the National Hospital of Pediatric from January 2007 to April 2014. Patients were selected by using inclusion criteria of Hussain K (2008). Mutations were identified in 32 cases (49.2%) including mutations of ABCC8 gene (28 cases; 43.1%), KCNJ11 (3 cases; 4.6%), HNF4A (1 case; 1.5%). 100% of cases with homozygous/compound heterozygous recessive mutations or one paternal dominant mutation of ABCC8 gene did not respond to diazoxide treatment and required 95% pancreatectomy. Molecular analysis using pancreas tissue after surgery from cases with one mutation of ABCC8 gene inherited from father confirmed focal lesion type. Other cases without identified mutations usually responded to diazoxide. In conclusions, children with Congenital Hyperinsulinism should be performed mutation analysis which helps in making diagnosis and treatment decision. Families of children with Congenital Hyperinsulinism should be given genetic counseling. Prenatal diagnosis should be performed as well as follow - up and treatment should be given to children with Congenital Hyperinsulinism immediately after birth.
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Increased plasma incretin concentrations identifies a subset of patients with persistent Congenital Hyperinsulinism without KATP channel gene defects.
The Journal of pediatrics, 2014Co-Authors: Yanqin Shi, Jacques Rahier, Sarah E. Flanagan, Sian Ellard, Raja Padidela, Hima Bindu Avatapalle, Mars Skae, Melanie Newbould, Lindsey Rigby, Peter E. ClaytonAbstract:Congenital Hyperinsulinism causes profound hypoglycemia, which may persist or resolve spontaneously. Among 13 children with Congenital Hyperinsulinism, elevated incretin hormone concentrations were detected in 2 with atypical, persistent disease. We suggest that incretin biomarkers may identify these patients, and that elevated hormone levels may contribute to their pathophysiology.
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Congenital Hyperinsulinism in a newborn with a novel homozygous mutation (p.Q392H) in the ABCC8 gene.
Journal of pediatric endocrinology & metabolism : JPEM, 2014Co-Authors: Deniz Anuk Ince, K Hussain, Sarah E. Flanagan, Nursel Muratoglu Sahin, Ayşe Ecevit, Abdullah Kurt, Sibel Tulgar Kinik, Aylin TarcanAbstract:Congenital Hyperinsulinism is the most frequent cause of persistent hypoglycemia in infancy. We present the case of a preterm, large-for-gestation-age infant with Congenital Hyperinsulinism who was found to have a novel p.Q392H homozygous mutation in the ABCC8 gene. The patient had severe brain damage, despite early diagnosis and appropriate management. The new mutations may provide an understanding of the prognosis and treatment of the disease. In addition, the data will help the family make informed decisions about future pregnancies.