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Abcc8-related Hyperinsulinism

First Report Of Diabetes Phenotype Due To A Loss-of-function Abcc8 Mutation Previously Known To Cause Congenital Hyperinsulinism

First Report Of Diabetes Phenotype Due To A Loss-of-function Abcc8 Mutation Previously Known To Cause Congenital Hyperinsulinism

First Report of Diabetes Phenotype due to a Loss-of-Function ABCC8 Mutation Previously Known to Cause Congenital Hyperinsulinism Theocharis Koufakis ,1 Amalia Sertedaki ,2 Elizabeth-Barbara Tatsi ,2 Christina-Maria Trakatelli ,1 Spyridon N. Karras ,1 Eleni Manthou ,1 Christina Kanaka-Gantenbein ,2 and Kalliopi Kotsa 1 1Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece 2Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Childrens Hospital, Athens, Greece Correspondence should be addressed to Kalliopi Kotsa ; [email protected] Received 10 February 2019; Revised 25 March 2019; Accepted 31 March 2019; Published 11 April 2019 Copyright 2019 Theocharis Koufakis et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Monogenic Diabetes is relatively rare, representing only 1-2% of total diabetes cases; nevertheless, it is often misdiagnosed primarily as type 1 diabetes, leading to unnecessary insulin therapy and delayed recognition of affected family members. In the present article, we describe a case of a young, male patient who presented with hyperglycemia in the absence of ketosis and following genetic testing; he proved to harbor the loss-of-function p.Arg1353His (c.4058G>A) mutation in the ABCC8 gene, inherited from his mother. This mutation has been previously described in patients with Congenital Hyperinsulinism. Furthermore, different mutations Continue reading >>

Familial Hyperinsulinism

Familial Hyperinsulinism

Synonyms: FHI, Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI) Familial hyperinsulinism (referred to as FHI in this GeneReview) is characterized by hypoglycemia that ranges from severe neonatal-onset, difficult-to-manage disease to childhood-onset disease with mild symptoms and difficult-to-diagnose hypoglycemia. Neonatal-onset disease manifests within hours to two days after birth. Childhood-onset disease manifests during the first months or years of life. In the newborn period, presenting symptoms may be nonspecific, including seizures, hypotonia, poor feeding, and apnea. In severe cases, serum glucose concentrations are typically extremely low and thus easily recognized, whereas in milder cases, variable and mild hypoglycemia may make the diagnosis more difficult. Even within the same family, disease manifestations can range from mild to severe. Individuals with autosomal recessive familial hyperinsulinism, caused by pathogenic variants in either ABCC8 or KCNJ11 (FHI-KATP), tend to be large for gestational age and usually present with severe refractory hypoglycemia in the first 48 hours of life; affected infants usually respond only partially to diet or medical management (i.e., diazoxide therapy) and thus may require pancreatic resection. Individuals with autosomal dominant FHI-KATP tend to be appropriate for gestational age at birth, to present at approximately age one year (range: 2 days - 30 years), and to respond to diet and diazoxide therapy. Exceptions to both of these generalities have been reported. FHI-GCK, caused by pathogenic variants in GCK, may be much milder than FHI-KATP; however, some persons have severe, diazoxide-unresponsive hypoglycemia. FHI-HADH, caused by pathogenic variants in HADH, tends to be relatively mild, although severe case Continue reading >>

Abcc8-related Congenital Hyperinsulinism Via Abcc8 Gene Sequencing With Cnv Detection - Preventiongenetics

Abcc8-related Congenital Hyperinsulinism Via Abcc8 Gene Sequencing With Cnv Detection - Preventiongenetics

ABCC8-Related Congenital Hyperinsulinism via ABCC8 Gene Sequencing with CNV Detection This test is also offered via our exome backbone with CNV detection ( click here ). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes. For ordering sequencing of targeted known variants, please proceed to our Targeted Variants landing page. The great majority oftests are completed within 20 days. In a cohort of 417 CHI patients studied at the Hyperinsulinism Center in The Children's Hospital of Philadelphia (CHOP), approximately 75% (160/213) of mutations, regardless of inheritance pattern, were identified in the ABCC8 gene via DNA sequencing (Snider, K. et al. J Clin Endocrinol Metab. 98(2):E355-363, 2013). Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous condition characterized by hypoglycemia (Glaser, B. et al. GeneReviews, 2003; Arnoux, J.B. et al. Early Hum Dev 86(5):287-294, 2010). The age of disease onset ranges from the neonatal period with severe forms to infancy or childhood with milder forms. Severe patients typically have extremely low serum glucose while milder cases present with variable hypoglycemia. Affected newborns also develop nonspecific symptoms including seizures, apnea, hypotonia, and poor feeding. Severity of disease manifestations can vary within the same family. CHI is genetically caused by defects in genes involved in regulation of insulin secretion from pancreatic beta-cells (Kapoor, R. et al. Eur J Endocrinol 168(4):557-564, 2013; Snider, K. et al. J Clin Endocrinol Metab 98(2):E355-363, 2013). ABCC8-related congenital hyperinsulinism can be inherited in an autosomal recessive or dominant manner. ABCC8 has 39 coding exons that encode the sulfonylu Continue reading >>

(pdf) Clinical Characteristics Of Recessive And Dominant Congenital Hyperinsulinism Due To Mutation(s) In The Abcc8/kcnj11 Genes Encoding The Atp-sensitive Potasium Channel In The Pancreatic Beta Cell

(pdf) Clinical Characteristics Of Recessive And Dominant Congenital Hyperinsulinism Due To Mutation(s) In The Abcc8/kcnj11 Genes Encoding The Atp-sensitive Potasium Channel In The Pancreatic Beta Cell

All content in this area was uploaded by Zeynep Siklar on Nov 25, 2015 J Pediatr Endocr Met 2011;24(11-12):10191023 2011 by Walter de Gruyter Berlin Boston. DOI 10.1515/JPEM.2011.347 *Corresponding author: Dr. Zeynep Siklar, Ankara Universitesi Tip Fak ltesi Pediatrik Endokrinoloji Bilim Dali 06100 Cebeci, Phone: + 90 5956791, E-mail: [email protected] Received July 10, 2011; accepted October 24, 2011; previously Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8 / KCNJ11 genes encoding the ATP-sensitive Gnl al 1 , Sarah E. Flanagan 2 , Blent Hacihamdio g lu 1 , Merih Berbero g lu 1 , Zeynep S iklar 1, * , Emel Okulu 3 , Ilke Mungan Akin 3 , Begum Atasay 3 , 1 Department of Pediatric Endocrinology , Medical School of 2 Institute of Biomedical and Clinical Science , Peninsula Medical School, Barrack Road, University of Exeter , UK 3 Department of Neonatology , Medical School of Ankara 4 Departmant of Pediatric Surgery , Medical School of Ankara Background: Recessive mutations in ABCC8/KCNJ11 of -cell K ATP channel generally cause severe medically unre- sponsive hyperinsulinemic hypoglycemia (HH). Rarer domi- nant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulin- ism. Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. To date the phenotype of patients with dominant mutations seems to be different from those with recessive mutations as the majority of patients are responsive to diazoxide therapy. Controversy exists on whether these dominant ABCC8 or KCNJ11 genes mutations predispose to Subjects: We report the clinical and genetic characteristics of ve patients wi Continue reading >>

Modeling Congenital Hyperinsulinism With Abcc8-deficient Human Embryonic Stem Cells Generated By Crispr/cas9

Modeling Congenital Hyperinsulinism With Abcc8-deficient Human Embryonic Stem Cells Generated By Crispr/cas9

Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by excess insulin secretion, which results in hypoglycemia. Mutation of sulfonylurea receptor 1 (SUR1), encoded by the ABCC8 gene, is the main cause of CHI. Here, we captured the phenotype of excess insulin secretion through pancreatic differentiation of ABCC8-deficient stem cells generated by the CRISPR/Cas9 system. ABCC8-deficient insulin-producing cells secreted higher insulin than their wild-type counterparts, and the excess insulin secretion was rescued by nifedipine, octreotide and nicorandil. Further, we tested the role of SUR1 in response to different potassium levels and found that dysfunction of SUR1 decreased the insulin secretion rate in low and high potassium environments. Hence, pancreatic differentiation of ABCC8-deficient cells recapitulated the CHI disease phenotype in vitro, which represents an attractive model to further elucidate the function of SUR1 and to develop and screen for novel therapeutic drugs. Congenital hyperinsulinism (CHI) refers to a group of rare genetic disorders that are characterized by excess insulin secretion by pancreatic -cells. As insulin is a key hormone in the regulation of blood glucose levels, excess insulin secretion leads to severe and persistent hypoglycemia 1 . Persistent hypoglycemia can induce jitteriness, lethargy, unresponsiveness and seizures and can increase the risk of brain injury 2 . The prevalence of CHI has increased from 1:50000 births to 1:2500 in the general population 3 . Therefore, a more relevant and specific disease model system that can recapitulate human CHI pathogenesis is desired for studying the disease mechanism and developing effective therapies. The molecular mechanisms of CHI involve anomalies in key genes that regulat Continue reading >>

Abcc8-related Hyperinsulinism

Abcc8-related Hyperinsulinism

ABCC8-related hyperinsulinism, also called congenital hyperinsulinism, is an inherited condition in which the pancreas releases inappropriately large quantities of the hormone insulin, leading to low blood sugar (hypoglycemia). When blood sugar drops to dangerously low levels, seizures and permanent brain damage may occur. If untreated, the condition could ultimately be fatal. ABCC8 refers to the name of the gene that causes this disease. Other genes have been identified which also cause hyperinsulinism. The pancreas normally secretes insulin in response to rising blood sugar. In people with ABCC8-related hyperinsulinism, the pancreas secretes insulin even without sugar consumption, thereby removing too much sugar from the blood. Infants with ABCC8-related hyperinsulinism tend to have significantly low blood sugar within the first few days of life. They often require immediate infusions of the sugar glucose to prevent seizures. These newborns are typically born larger than normal and may show difficulty feeding, poor muscle tone, and breathing problems. In some people with ABCC8-related hyperinsulinism, symptoms do not appear until later in childhood. The low blood sugar associated with the condition can also range from mild to severe depending on the individual, and varies even among members of the same family. Early and aggressive treatment is important to avoid permanent brain damage. How common is ABCC8-related Hyperinsulinism? ABCC8-related hyperinsulinism affects roughly 1 in 50,000 Europeans. It is particularly common among people of Finnish and Saudi Arabian descent, where the disease may affect as many as 1 in 2,500. A certain genetic mutation is prevalent in people of Ashkenazi Jewish descent. How is ABCC8-related Hyperinsulinism treated? Treatments for ABCC8 Continue reading >>

Paternally Inherited Abcc8 Mutation Causing Diffuse Congenital Hyperinsulinism

Paternally Inherited Abcc8 Mutation Causing Diffuse Congenital Hyperinsulinism

HH is a cause of severe hypoglycaemia in the newborn period. Paternal mutations in ABCC8/KCNJ11 can lead to diffuse or focal disease. 18F-DOPA-PET/CT scan is the current imaging of choice for localising focal lesions. Gallium-68 tetra-aza-cyclododecane-NNNN--tetra-acetate octreotate PET scan is not a useful imaging tool for localising focal lesions. The molecular mechanism by which a heterozygous ABCC8 mutation leads to diffuse disease is currently unclear. Focal lesions are curable by lesionectomy and so genetic studies in patients with HH must be followed by imaging using 18F-DOPA-PET/CT scan. Congenital hyperinsulinism (CHI) leads to severe hyperinsulinaemic hypoglycaemia (HH) in the neonatal, infancy and childhood periods. The genetic basis of CHI is beginning to be understood. Genetic studies are indicated in infants with persistent hypoglycaemia, hypoketonaemia and low fatty acid levels while requiring a glucose infusion rate (GIR) of more than 8 mg/kg per min to maintain euglycaemia (3.56.5 mmol/l). Most of the CHI cases are due to recessive or dominant mutations of ABCC8/KCNJ11 genes. The majority of the recessive mutations are resistant to medical treatment. Dominant forms are characterised by the various presentations and treatment responses. Initial management is aimed at correction of hypoglycaemia to prevent long-term neuro-disability. The response to diazoxide therapy is the key to managing CHI. Diazoxide unresponsiveness is considered as an indication for a rapid mutational analysis of ABCC8/KCNJ11 genes. Fluorine-18-l-dihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA-PET/CT) scan is recommended if the genetic studies are suggestive of focal disease, which can then be cured by laparoscopic excision. We present the first ca Continue reading >>

Congenital Hyperinsulinism

Congenital Hyperinsulinism

"PHHI" redirects here. It is not to be confused with Wheeler Army Airfield . Congenital hyperinsulinism ,CHI, is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. [4] [3] Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. These conditions are present at birth and most become apparent in early infancy. Mild cases can be treated by frequent feedings, more severe cases can be controlled by medications that reduce insulin secretion or effects [4] [5] Insulin (which this condition creates in excess) Hypoglycemia in early infancy can cause jitteriness, lethargy , unresponsiveness, or seizures . [1] The most severe forms may cause macrosomia in utero, producing a large birth weight, often accompanied by abnormality of the pancreas. Milder hypoglycemia in infancy causes hunger every few hours, with increasing jitteriness or lethargy. Milder forms have occasionally been detected by investigation of family members of infants with severe forms, adults with the mildest degrees of congenital hyperinsulinism have a decreased tolerance for prolonged fasting. Other presentations are: [4] [5] [3] [6] The variable ages of presentations and courses suggest that some forms of congenital hyperinsulinism, especially those involving abnormalities of KATP channel function, can worsen or improve with time the potential harm from hyperinsulinemic hypoglycemia depends on the severity, and duration. Children who have recurrent hyperinsulinemic hypoglycemia in infancy can suffer harm to the brain [4] The cause of congenital hyperinsulinism has been linked to anomalies in nine different genes. [7] The diffuse form of this condition is inherited via the autosomal recessive manne Continue reading >>

Omim Entry - # 256450 - Hyperinsulinemic Hypoglycemia, Familial, 1; Hhf1

Omim Entry - # 256450 - Hyperinsulinemic Hypoglycemia, Familial, 1; Hhf1

A number sign (#) is used with this entry because of evidence that familial hyperinsulinemic hypoglycemia-1 (HHF1) is caused by homozygous or compound heterozygous mutation in the ABCC8 gene (600509), encoding the SUR1 subunit of the pancreatic beta cell inwardly rectifying potassium channel, on chromosome 11p15. Familial hyperinsulinism, also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur (Thornton et al., 1998). Genetic Heterogeneity of Hyperinsulinemic Hypoglycemia HHF2 (601820) is caused by mutation in the KCNJ11 gene (600937), on chromosome 11p15.1. HHF3 (602485) is caused by mutation in the glucokinase gene (GCK; 138079) on chromosome 7p15-p13. HHF4 (609975) is caused by mutation in the HADH gene (601609) on chromosome 4q22-q26. HHF5 (609968) is caused by mutation in the insulin receptor gene (INSR; 147670) on chromosome 19p13.2. HHF6 (606762) is caused by mutation in the GLUD1 gene (138130) on chromosome 10q23.3. HHF7 (610021) is caused by mutation in the SLC16A1 (600682) on chromosome 1p13.2-p12. There is evidence of further genetic heterogeneity of HHF. The term nesidioblastosis (meaning neoformation of islets of Langerhans from pancreatic duct epithelium) was coined by Laidlaw (1938) to describe the diffuse abnormality of the pancreas in which there is extensive, often disorganized formation of new islets. 'Nesidio' comes from a Greek word for islet. Yakovac et al. (1971) was first to report nesidioblastosis i Continue reading >>

Frontiers | Neonatal Diabetes And Congenital Hyperinsulinism Caused By Mutations In Abcc8/sur1 Are Associated With Altered And Opposite Affinities For Atp And Adp | Endocrinology

Frontiers | Neonatal Diabetes And Congenital Hyperinsulinism Caused By Mutations In Abcc8/sur1 Are Associated With Altered And Opposite Affinities For Atp And Adp | Endocrinology

Front. Endocrinol., 15 April 2015 | Neonatal diabetes and congenital hyperinsulinism caused by mutations in ABCC8/SUR1 are associated with altered and opposite affinities for ATP and ADP 1Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA 2Pacific Northwest Diabetes Research Institute, Seattle, WA, USA ATP-sensitive K+ (KATP) channels composed of potassium inward-rectifier type 6.2 and sulfonylurea receptor type 1 subunits (Kir6.2/SUR1)4 are expressed in various cells in the brain and endocrine pancreas where they couple metabolic status to membrane potential. In -cells, increases in cytosolic [ATP/ADP]c inhibit KATP channel activity, leading to membrane depolarization and exocytosis of insulin granules. Mutations in ABCC8 (SUR1) or KCNJ11 (Kir6.2) can result in gain or loss of channel activity and cause neonatal diabetes (ND) or congenital hyperinsulinism (CHI), respectively. SUR1 is reported to be a Mg2+-dependent ATPase. A prevailing model posits that ATP hydrolysis at SUR1 is required to stimulate openings of the pore. However, recent work shows nucleotide binding, without hydrolysis, is sufficient to switch SUR1 to stimulatory conformations. The actions of nucleotides, ATP and ADP, on ND (SUR1E1506D) and CHI (SUR1E1506K) mutants, without Kir6.2, were compared to assess both models. Both substitutions significantly impair hydrolysis in SUR1 homologs. SUR1E1506D has greater affinity for MgATP than wildtype; SUR1E1506K has reduced affinity. Without Mg2+, SUR1E1506K has a greater affinity for ATP4 consistent with electrostatic attraction between ATP4, unshielded by Mg2+, and the basic lysine. Further analysis of ND and CHI ABCC8 mutants in the second transmembrane and nucleotide-binding domains (TMD2 and NBD2) found a relation between their Continue reading >>

Abcc8-related Familial Hyperinsulinism

Abcc8-related Familial Hyperinsulinism

What Is ABCC8-Related Familial Hyperinsulinism? ABCC8-related familial hyperinsulinism is an inherited condition of disrupted insulin response. In a healthy individual, the pancreas normally secretes a hormone called insulin in response to rising blood sugar after eating carbohydrates. In familial hyperinsulinism, insulin is secreted even without carbohydrate consumption. An excess of insulin released into the blood can cause blood sugars to drop to dangerously low levels (hypoglycemia). One cause of familial hyperinsulinism is due to mutations in the ABCC8 gene. Infants with familial hyperinsulinism tend to have significantly low blood sugar within the first few days of life. These newborns are typically larger at birth and may have difficulty feeding, poor muscle tone, and breathing problems. These infants often require immediate infusions of glucose to help raise blood sugar levels and prevent seizures. Prolonged hypoglycemia can also lead to permanent brain damage. In some individuals with familial hyperinsulinism, symptoms do not appear until later in childhood. The low blood sugar associated with the condition can also range from mild to severe depending on the individual, and it can vary even among members of the same family. Rarely, specific mutations in the ABCC8 gene cause neonatal diabetes. In neonatal diabetes, not enough insulin is secreted, and blood sugar increases to dangerously high levels (hyperglycemia). Infants with neonatal diabetes tend to have high blood sugar levels between birth and six months of age. These newborns are typically smaller at birth than normal and may have difficulty feeding, severe dehydration, glucose in the urine, and excessive urination. While some with neonatal diabetes need lifelong treatment to prevent high blood sugar, ot Continue reading >>

Pathological Features Of Aberrant Pancreatic Development In Congenital Hyperinsulinism Due To Abcc8 Mutations

Pathological Features Of Aberrant Pancreatic Development In Congenital Hyperinsulinism Due To Abcc8 Mutations

2008 by the Association of Clinical Scientists, Inc. Pathological Features of Aberrant Pancreatic Development in Congenital Hyperinsulinism Due to ABCC8 Mutations 1Departments of Molecular and Human Genetics, 2Surgery, 3Pediatrics, and 4Pathology, Baylor College of Medicine, Houston, Texas Address correspondence to Nina Tatevian, M.D., Ph.D., Department of Pathology, Texas Childrens Hospital, 6621 Fannin St. MC2-2261, Houston TX 77030, USA; tel 832 824 1868; fax 832 825 1032; e-mail nxtatevi{at}texaschildrenshospital.org. We describe a patient with congenital hyperinsulinism with previously unreported pathological findings including normal to decreased number of insulin-positive cells with very few enlarged nuclei, aberrant distribution of glucagon-positive cells, and a non-insulin producing adenomatous focus of unusual morphology. Molecular analysis showed that the patient was a compound heterozygote for two mutations of the ABCC8 gene: a previously unreported nonsense mutation (R841X) and a missense mutation (D1471N) that has been previously described. This case suggests that abnormal function of ABCC8 may result in aberrant pancreatic development. Congenital hyperinsulinism (CHI, MIM 256450 ), characterized by profound hypoglycemia related to inappropriate insulin secretion, may be associated with either diffuse insulin hypersecretion or focal adenomatous hyperplasia [ 1 ]. Both forms of CHI have similar clinical presentations, but they differ in management and molecular pathogenesis. Diffuse hyperinsulinism, characterized by presence of enlarged islet cell nuclei throughout the pancreas, is due to recessive mutations in ABCC8 [ 2 , 3 ] or KCNJ11 [ 4 ]. All -cells are functionally abnormal, and infants with diffuse hyperinsulinism require nearly total pancreatectomy Continue reading >>

Congenital Hyperinsulinism - Genetics Home Reference

Congenital Hyperinsulinism - Genetics Home Reference

What does it mean if a disorder seems to run in my family? What is the prognosis of a genetic condition? Congenital hyperinsulinism affects approximately 1 in 50,000 newborns. This condition is more common in certain populations, affecting up to 1 in 2,500 newborns. What information about a genetic condition can statistics provide? Why are some genetic conditions more common in particular ethnic groups? Congenital hyperinsulinism is caused by mutations in genes that regulate the release (secretion) of insulin, which is produced by beta cells in the . Insulin clears excess sugar (in the form of glucose) from the bloodstream by passing glucose into cells to be used as energy. congenital hyperinsulinism lead to over-secretion of insulin from beta cells. Normally, insulin is secreted in response to the amount of glucose in the bloodstream: when glucose levels rise, so does Congenital hyperinsulinism can have different inheritance patterns, usually depending on the form of the condition. At least two forms of the condition have been identified. The most common form is the diffuse form, which occurs when all of the beta cells in the pancreas secrete too much insulin. The focal form of congenital hyperinsulinism occurs when only some of the beta cells over-secrete insulin. congenital hyperinsulinism is inherited in an , which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Less frequently, the diffuse form is inherited in an , which means one copy of the altered gene in each cell is sufficient to cause the disorder. congenital hyperinsulinism is more complex. For most genes, both copies are t Continue reading >>

Abcc8 Gene - Genecards | Abcc8 Protein | Abcc8 Antibody

Abcc8 Gene - Genecards | Abcc8 Protein | Abcc8 Antibody

Leucine-induced hypoglycemia (LIH) [MIM:240800]: Rare cause of hypoglycemia and is described as a condition in which symptomatic hypoglycemia is provoked by high protein feedings. Hypoglycemia is also elicited by administration of oral or intravenous infusions of a single amino acid, leucine. {ECO:0000269 PubMed:15356046}. Note=The disease is caused by mutations affecting the gene represented in this entry. Familial hyperinsulinemic hypoglycemia 1 (HHF1) [MIM:256450]: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. {ECO:0000269 PubMed:10202168, ECO:0000269 PubMed:10334322, ECO:0000269 PubMed:10615958, ECO:0000269 PubMed:11018078, ECO:0000269 PubMed:11226335, ECO:0000269 PubMed:11867634, ECO:0000269 PubMed:12364426, ECO:0000269 PubMed:12941782, ECO:0000269 PubMed:15562009, ECO:0000269 PubMed:15579781, ECO:0000269 PubMed:15807877, ECO:0000269 PubMed:16357843, ECO:0000269 PubMed:16429405, ECO:0000269 PubMed:24814349, ECO:0000269 PubMed:25720052, ECO:0000269 PubMed:8650576, ECO:0000269 PubMed:8751851, ECO:0000269 PubMed:8923011, ECO:0000269 PubMed:9618169, ECO:0000269 PubMed:9648840, ECO:0000269 PubMed:9769320}. Note=The disease is caused by mutations affecting the gene represented in this entry. Diabetes mellitus, permanent neonatal (PNDM) [MIM:606176]: A rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy. {ECO:0000269 PubMed:16613899, ECO:0000269 PubMed:16885549, ECO:0000269 PubMed:17213273, ECO:0000269 PubMed:17668386}. Note=The disease is caused by Continue reading >>

Abcc8-related Hyperinsulinism

Abcc8-related Hyperinsulinism

Some carriers show no symptoms of ABCC8-related hyperinsulinism while others have symptoms ranging from congenital hyperinsulinism to type 2 diabetes mellitus in adulthood. All carriers are at an increased risk of having a child with ABCC8-related hyperinsulinism. ABCC8-related hyperinsulinism is an inherited disorder characterized by hypoglycemia, or low blood sugar. Individuals with ABCC8-related hyperinsulinism release insulin into the blood stream even in the absence of glucose. The low level of sugar in the blood increases the risk for seizures and brain damage and can ultimately lead to death. Treatment of individuals with ABCC8-related hyperinsulinism includes glucose infusions as well as other medications and frequent eating to prevent complications associated with hypoglycemia. In some cases it may be necessary to surgically remove most of the pancreas. Even with treatment, some individuals may have some degree of brain damage or learning disabilities. In general, individuals have two copies of the ABCC8 gene. Individuals with ABCC8-related hyperinsulinism typically have pathogenic variants in both copies of their ABCC8 genes, one inherited from each parent. In addition to the autosomal recessive form, ABCC8-related hyperinsulinism caused by a single ABCC8 variant, E1506K, has been associated with symptoms ranging from congenital hyperinsulinism to type 2 diabetes mellitus in adulthood. Determining which screens or set of screens are right for you will depend on where you are in your reproductive journey. Tell us where you are today so you can learn more about how to move forward tomorrow. Continue reading >>

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