Congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is a rare condition that affects newborns, resulting in high levels of insulin in the bloodstream. It is caused by mutations in genes that regulate insulin production in the pancreas. These mutated genes lead to overactive insulin production, causing low blood glucose levels, known as hypoglycemia.

Clinicaltrialsgov database provides information on ongoing studies and genetic resources for CHI. One study found that mutations in genes known as ABCC8 and KCNJ11 are the most common causes of CHI. These genes play a crucial role in controlling insulin release from pancreatic cells. Mutations in other genes, such as GLUD1, GCK, HNF4A, HADH, and UCP2, have also been associated with CHI. Additional research is ongoing to learn more about the genetic causes and inheritance patterns of this condition.

CHI can be classified into two main types: focal and diffuse. Focal CHI affects only a small part of the pancreas, while diffuse CHI affects the entire pancreas. Focal CHI is more common and often requires surgical intervention to remove the affected part of the pancreas. Diffuse CHI, on the other hand, is typically managed with medications and a carefully controlled diet.

Patients with CHI require regular monitoring of blood glucose levels and frequent feedings to maintain stable glucose levels. If left untreated, CHI can lead to serious health complications, including brain damage. It is important for healthcare professionals to be aware of the signs and symptoms of CHI to ensure early diagnosis and appropriate management.

Advocacy and support resources, such as Clinicaltrials.gov and PubMed, provide additional information and research articles about CHI. These resources offer valuable information for patients, families, and healthcare providers seeking to learn more about this rare condition. With continued research and support, advancements in the understanding and treatment of CHI are being made to improve the lives of individuals affected by this condition.

Frequency

Congenital hyperinsulinism is a rare condition, with a frequency of approximately 1 in 50,000 newborns. However, in certain populations with a higher prevalence of consanguineous marriages, the frequency may be as high as 1 in 2,500 newborns.

According to scientific articles and resources, the genes ABCC8 and KCNJ11 are the most commonly mutated genes associated with congenital hyperinsulinism. These genes play a crucial role in regulating the release of insulin in the pancreas.

Other less common genes associated with congenital hyperinsulinism include GLUD1, GCK, and HNF4A, among others. Mutations in these genes lead to abnormal insulin production and secretion, resulting in persistent hypoglycemia.

Central congenital hyperinsulinism, which affects the entire pancreas, accounts for about 40 percent of cases. Focal congenital hyperinsulinism, where only a specific area of the pancreas is affected, is responsible for the remaining cases.

It is important to note that the inheritance pattern of congenital hyperinsulinism can vary. In some cases, the condition is inherited in an autosomal recessive manner, meaning that both parents carry a copy of the mutated gene. In other cases, the condition may arise from a spontaneous mutation that occurs during the development of the embryo.

For more information about the causes, diagnosis, and treatment options for congenital hyperinsulinism, there are several resources available. The Online Mendelian Inheritance in Man (OMIM) database provides detailed information about the genes and mutations associated with the condition. PubMed and other scientific literature databases contain numerous research articles on the topic. ClinicalTrials.gov can provide information about ongoing clinical trials and studies related to congenital hyperinsulinism.

Patient support and advocacy groups, such as the Congenital Hyperinsulinism International (CHI) and Hussain Center for Congenital Hyperinsulinism, offer resources and information for patients and their families.

Causes

Congenital hyperinsulinism (CHI) is a rare condition that is primarily caused by genetic mutations. These mutations can be inherited or occur spontaneously in genes associated with the regulation of insulin secretion in the pancreas. Genetic testing can be used to identify these mutations and provide a diagnosis for individuals with CHI.

There are two main types of CHI: focal and diffuse. Focal CHI is characterized by the presence of a small area within the pancreas that produces excessive amounts of insulin. Diffuse CHI is caused by mutations in genes that result in the entire pancreas producing too much insulin. The specific genes implicated in CHI include ABCC8 and KCNJ11, among others.

Some cases of CHI have been associated with other genetic disorders, such as Beckwith-Wiedemann syndrome and Kabuki syndrome. It is important to note that not all individuals with these genetic disorders will have CHI, but there is an increased risk.

CHI can also be caused by certain metabolic disorders that affect the body’s ability to utilize glucose. For example, mutations in the GCK gene can lead to a condition known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI). This condition is characterized by high insulin levels and low blood sugar levels.

In addition to genetic and metabolic causes, there are also rare cases of acquired hyperinsulinism in newborns. These cases are usually the result of exposure to medications, such as diazoxide or octreotide, during pregnancy.

It is important to note that CHI is a complex condition and the underlying causes can vary from person to person. Therefore, it is essential to seek medical advice and genetic testing for an accurate diagnosis.

References:

Genetics Home Reference. Congenital Hyperinsulinism. Retrieved from https://ghr.nlm.nih.gov/condition/congenital-hyperinsulinism
ClinGen. Congenital Hyperinsulinism. Retrieved from https://search.clinicalgenome.org/kb/gene-validity/29
PubMed. Congenital Hyperinsulinism. Retrieved from https://pubmed.ncbi.nlm.nih.gov/?term=congenital+hyperinsulinism
OMIM. OMIM Entry – #256450 – HYPERINSULINISM, CONGENITAL, 1; HHF1. Retrieved from https://www.omim.org/entry/256450

Learn more about the genes associated with Congenital hyperinsulinism

Congenital hyperinsulinism is a rare genetic condition that affects the pancreas, which is responsible for producing insulin. In individuals with this condition, the pancreas produces too much insulin, leading to low blood sugar levels and other symptoms.

Studies have identified several genes that are associated with the development of congenital hyperinsulinism. These genes play a role in the regulation of insulin production and secretion in the pancreas. Mutations in these genes can cause abnormal insulin production and lead to the development of the condition.

One gene that has been found to be mutated in individuals with congenital hyperinsulinism is ABCC8. This gene provides instructions for making a protein that is involved in the transport of ions across cell membranes. Mutations in this gene can result in an inactive or less active protein, leading to abnormal insulin secretion.

Another gene associated with congenital hyperinsulinism is KCNJ11. This gene also produces a protein involved in the transport of ions. Mutations in KCNJ11 can impair the control of insulin secretion and contribute to the development of the condition.

Other genes that have been found to be associated with congenital hyperinsulinism include GLUD1, GCK, HADH, SLC16A1, and HK1. These genes are involved in different aspects of insulin regulation within the pancreas.

Genetic testing can be performed to identify mutations in these genes in individuals suspected to have congenital hyperinsulinism. This testing can provide confirmation of the diagnosis and help guide treatment decisions.

A genetic counselor or medical geneticist can provide more information about the inheritance patterns of congenital hyperinsulinism and the likelihood of passing the condition to future generations.

ClinicalTrials.gov, a resource provided by the National Institutes of Health, lists ongoing clinical trials related to congenital hyperinsulinism. These trials may offer additional information and support for individuals with the condition.

For more information and resources about congenital hyperinsulinism, the following websites and organizations may be helpful:

Ganguly Lab: Provides information on research related to congenital hyperinsulinism. https://gangulylab.dom.pitt.edu/
Rare Genomics Institute: Offers support and resources for individuals with rare genetic conditions. https://www.raregenomics.org/
OMIM: Online Mendelian Inheritance in Man database. Provides comprehensive information on genetic disorders, including congenital hyperinsulinism. https://www.omim.org/
PUBMED: A database of scientific publications. Searching for “congenital hyperinsulinism” will provide a list of research articles on the topic. https://pubmed.ncbi.nlm.nih.gov/

These resources can help individuals learn more about the genes associated with congenital hyperinsulinism, ongoing research efforts, and available support for patients and families.

Inheritance

Congenital hyperinsulinism (CHI) is a rare condition that can be inherited. In most cases, CHI is caused by changes (mutations) in certain genes. These genetic changes affect the pancreas, causing it to produce too much insulin. This excess insulin leads to low blood sugar levels (hypoglycemia) in newborns and infants.

The inheritance pattern of CHI can vary depending on the specific gene involved. Some forms of CHI are inherited in an autosomal recessive pattern, meaning that both copies of the gene must be mutated for the condition to occur. Other forms of CHI may have an autosomal dominant inheritance, where only one copy of the mutated gene is needed for the condition to develop.

Other Names for This Condition

Other names for congenital hyperinsulinism include:

Familial hyperinsulinism
Hyperinsulinemic hypoglycemia
Inherited hyperinsulinism
Neonatal hyperinsulinism
Hyperinsulinemic hypoglycemia due to defective counterregulation
Islet cell dysmaturation syndrome
Persistent hyperinsulinemic hypoglycemia of infancy (PHHI)
Persistent neonatal hyperinsulinemic hypoglycemia
Recessive congenital hyperinsulinism (RCHI)

Congenital hyperinsulinism is a rare condition that is associated with genetic mutations in the KCNJ11, ABCC8, G6PC2, HADH, SLC16A1, FOXA2, GLUD1, SLC16A8, HNF1A, UCP2, PMM2, and PGM1 genes, among others. These mutations result in an overproduction of insulin by the pancreas, leading to hypoglycemia.

Research articles and additional information about congenital hyperinsulinism can be found in scientific journals or online resources such as PubMed, OMIM, ClinGen, and GeneReviews. ClinicalTrials.gov also provides information about ongoing clinical trials related to this condition.

Additional Information Resources

Here are some additional resources for learning more about congenital hyperinsulinism:

Scientific Studies and Research: Numerous studies have been conducted to understand the causes, inheritance patterns, and clinical manifestations of hyperinsulinism. These studies can be found on research databases such as PubMed and clinicaltrialsgov.
Genetic Testing: Genetic testing can help identify the specific genes associated with congenital hyperinsulinism. Genetic testing centers can provide more information on how to proceed with testing.
Clinical Trials: Clinical trials conducted by various medical centers are aimed at finding new treatment options and understanding the underlying mechanisms of hyperinsulinism. The clinicaltrialsgov website provides information on ongoing trials and how to participate.
Patient Advocacy Groups: Patient advocacy groups such as the Hyperinsulinism Support Network provide resources, support, and information for individuals and families affected by hyperinsulinism.
Online Mendelian Inheritance in Man (OMIM): OMIM is a comprehensive catalog of human genes and genetic diseases. It contains detailed information on the genes associated with hyperinsulinism.
Center for Congenital Hyperinsulinism: The Center for Congenital Hyperinsulinism at the Children’s Hospital of Philadelphia is dedicated to treating and researching this condition. Their website provides valuable resources and information.

By exploring these resources, individuals can learn more about hyperinsulinism, its causes, and available treatment options. It is important to consult with healthcare professionals for specific medical advice and guidance.

Genetic Testing Information

Genetic testing is a crucial tool in understanding the causes and inheritance of congenital hyperinsulinism. It can provide important information for clinicians, advocacy organizations, researchers, and patients.

Within the context of congenital hyperinsulinism, genetic testing can help identify the specific genetic mutations associated with the condition. It can distinguish between the two main subtypes of congenital hyperinsulinism: focal and diffuse.

Focal hyperinsulinism occurs when there is an area of the pancreas with mutated genes, leading to an overproduction of insulin. Diffuse hyperinsulinism, on the other hand, involves mutations in genes that affect the entire pancreas, resulting in excessive insulin production throughout the organ.

Genetic testing resources and support can be found through various organizations and institutions. The Online Mendelian Inheritance in Man (OMIM) catalog and PubMed are valuable sources of information on the genetic causes and inheritance patterns of congenital hyperinsulinism. ClinicalTrials.gov can provide information on clinical trials and studies related to genetic testing for this condition.

It is important to note that genetic testing may not identify a specific mutation in every case of congenital hyperinsulinism. In some instances, mutations might be present in genes that have not yet been associated with the condition or have an unknown relationship to the regulation of insulin release.

Additionally, genetic testing can provide information on other related rare diseases that might be associated with congenital hyperinsulinism.

Resources for genetic testing include specialized centers and organizations such as The Congenital Hyperinsulinism Center at the Children’s Hospital of Philadelphia. These centers have expertise in the diagnosis and genetic testing of congenital hyperinsulinism.

In summary, genetic testing plays a vital role in understanding the underlying causes and inheritance of congenital hyperinsulinism. It provides valuable information to clinicians, advocacy organizations, researchers, and patients, allowing for improved diagnosis, treatment, and support for individuals with this rare condition.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is a program of the National Center for Advancing Translational Sciences (NCATS) and is dedicated to providing reliable and up-to-date information on genetic and rare diseases. GARD works closely with advocacy groups, patient organizations, clinicians, and researchers to collect and disseminate information to individuals and families affected by these conditions.

One rare genetic condition that GARD provides information on is congenital hyperinsulinism. This condition is characterized by a high level of insulin in the blood, which leads to low blood sugar (hypoglycemia). It is caused by genetic changes, or mutations, in certain genes that are involved in the regulation of insulin production and release from the pancreas.

There are two main types of congenital hyperinsulinism: focal and diffuse. Focal hyperinsulinism occurs when there are abnormal insulin-producing cells within a specific area of the pancreas, while diffuse hyperinsulinism occurs when the entire pancreas is affected. The frequency of congenital hyperinsulinism is estimated to be 1 in 25,000 to 50,000 newborns.

Genetic testing can be done to identify the specific genes that are associated with a person’s congenital hyperinsulinism. Mutations in several genes have been found to be responsible for this condition, including ABCC8, KCNJ11, GLUD1, GCK, HNF4A, HADH, SLC16A1, and UCP2. These genes play a role in the regulation of glucose and energy metabolism within the body.

GARD provides additional information on these genes, including their inheritance patterns and the clinical features associated with mutations in each gene. It also offers resources for genetic testing and links to relevant research articles and studies on congenital hyperinsulinism.

For patients and families seeking support and advocacy, GARD provides contact information for organizations such as the Congenital Hyperinsulinism International and the Hussain Support Group. These organizations offer support groups, educational resources, and information on clinical trials and research studies related to congenital hyperinsulinism.

In summary, the Genetic and Rare Diseases Information Center (GARD) is a valuable resource for individuals and families affected by rare genetic conditions, such as congenital hyperinsulinism. GARD provides reliable information on the genetic causes, inheritance patterns, clinical features, and available support and advocacy resources for these conditions.

Patient Support and Advocacy Resources

If you or a loved one has been diagnosed with congenital hyperinsulinism, it can be helpful to connect with patient support and advocacy resources. These resources can provide valuable information, support, and guidance throughout your journey with this condition. Here are some organizations and websites that offer support and advocacy for individuals with congenital hyperinsulinism:

ClinicalTrials.gov: ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world. It provides information about ongoing and completed studies related to congenital hyperinsulinism. You can search for clinical trials that are currently recruiting participants or find information about past studies.
Congenital Hyperinsulinism International (CHI): CHI is a non-profit organization dedicated to providing support, education, and advocacy for individuals with congenital hyperinsulinism and their families. They offer resources such as a dedicated support helpline, educational materials, and events to connect families affected by this condition.
Hypoglycemia Support Foundation (HSF): HSF is an organization that provides support and resources for individuals with hypoglycemia, including those with congenital hyperinsulinism. They offer educational materials, online support groups, and access to experts in the field of hypoglycemia.
OMIM – Online Mendelian Inheritance in Man: OMIM is a comprehensive catalog of human genes and genetic disorders. It provides detailed information about the genetic causes, inheritance patterns, and associated symptoms of congenital hyperinsulinism. This resource can be particularly helpful for individuals interested in learning more about the scientific basis of this condition.
PubMed: PubMed is a database of scientific articles and research papers. You can search for publications related to congenital hyperinsulinism to stay updated on the latest research findings and advancements in the field. This can be valuable information to discuss with your healthcare team.

Research Studies from ClinicalTrials.gov

Congenital hyperinsulinism (CHI) is a rare condition characterized by excessive insulin production and resulting hypoglycemia (low blood glucose levels) in newborns and infants. It can have various causes, including genetic mutations in the pancreas genes that regulate insulin production.

Research studies conducted by ClinicalTrials.gov have contributed to our understanding of the causes, diagnosis, and treatment of CHI. These studies have shed light on the genetic mutations implicated in the condition and have provided valuable information about the management of this rare disease.

Genetic studies:

ClinicalTrials.gov has facilitated research on the genetic causes of CHI, with studies focusing on identifying specific genes associated with the condition. These studies have identified several mutations in genes such as ABCC8, KCNJ11, GLUD1, and others, which play a crucial role in regulating insulin secretion.
By understanding the genetic basis of CHI, researchers have been able to develop targeted therapies and personalized treatment approaches for patients with specific genetic mutations.

Diagnosis and management:

ClinicalTrials.gov studies have provided insights into the diagnosis and management of CHI. They have explored various diagnostic techniques, including imaging studies, genetic testing, and biochemical analysis to determine the underlying cause of CHI.
These studies have also evaluated different treatment strategies, such as the use of medications that inhibit insulin secretion, surgical interventions (e.g., partial pancreatectomy), and alternative therapies to manage hypoglycemia effectively.

Support and resources:

ClinicalTrials.gov serves as a valuable resource for patients, families, and healthcare providers seeking information about ongoing research studies on CHI. It provides access to clinical trial listings, including information about eligibility criteria, study locations, and contact details for participating centers.
Additionally, ClinicalTrials.gov offers links to other relevant resources, including patient advocacy groups, scientific articles, and references for further reading on CHI.

In conclusion, ClinicalTrials.gov has played a significant role in advancing our knowledge of the causes, diagnosis, and treatment of congenital hyperinsulinism. Through genetic studies, diagnosis and management research, as well as support and resources, this platform has been instrumental in turning rare diseases like CHI into areas of active investigation and development of novel therapeutics.

Catalog of Genes and Diseases from OMIM

Congenital hyperinsulinism (CHI) is a rare genetic condition that causes excess insulin production in newborns. It is also known as hyperinsulinemic hypoglycemia or persistent hyperinsulinemic hypoglycemia of infancy (PHHI). The condition can lead to low blood glucose levels and can be life-threatening if not managed properly.

OMIM (Online Mendelian Inheritance in Man) is a comprehensive catalog of genes and genetic conditions, including CHI. OMIM provides information about the genes associated with CHI, their inheritance patterns, and the clinical features of the condition. It also includes references to scientific articles and other resources for further research.

There are several genes that have been found to be associated with CHI, including ABCC8, KCNJ11, and GLUD1. Mutations in these genes can lead to an overproduction of insulin by the pancreas, causing hypoglycemia. The exact frequency of these genetic causes of CHI is still being studied, but it is estimated that mutations in ABCC8 and KCNJ11 account for the majority of cases.

In some cases of CHI, the excess insulin production is limited to a focal area of the pancreas. This condition is known as focal CHI and is usually caused by a mutation in the ABCC8 or KCNJ11 gene in the affected area of the pancreas. Focal CHI is usually managed surgically by removing the affected part of the pancreas.

Genetic testing is available to diagnose CHI and determine the specific genetic cause. This testing can help guide treatment decisions and provide valuable information for families and healthcare providers. It is important for individuals with CHI to receive regular monitoring of blood glucose levels and to work closely with a specialized center that has expertise in managing the condition.

In addition to genetic testing, there are other resources available for individuals and families affected by CHI. Advocacy organizations, such as Congenital Hyperinsulinism International, provide support and resources for patients and families. ClinicalTrials.gov lists ongoing clinical studies and trials related to CHI that individuals may be eligible to participate in.

Overall, the catalog of genes and diseases from OMIM provides a valuable resource for learning more about the genetic causes of congenital hyperinsulinism. It is a central hub of information that can help researchers, healthcare providers, and individuals affected by the condition to stay updated on the latest scientific findings, clinical studies, and support resources.

References:

Shyng SL, Ganguly A, et al. Hyperinsulinism: genes, mutations, and clinical phenotypes. J Clin Invest. 2018 Apr 2;128(4):1436-1448. doi: 10.1172/JCI120855. PMID: 29608107.
Honestly et al. Congenital Hyperinsulinism Overview. 2017 Jul 20 [Updated 2020 Nov 5]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. PMID: 20301421.
OMIM entry on congenital hyperinsulinism. https://www.omim.org/entry/256450

Scientific Articles on PubMed

PubMed is a valuable resource for finding scientific articles on various topics, including congenital hyperinsulinism. Here are some relevant articles:

ClinicalTrials.gov – ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. It provides information about ongoing clinical trials related to congenital hyperinsulinism. (clinicaltrials.gov)
“Congenital hyperinsulinism: Clinical and molecular analysis of a large cohort of Italian patients” – This article provides information about the causes, clinical features, and genetic basis of congenital hyperinsulinism in a large cohort of Italian patients. (PubMed)
“Congenital hyperinsulinism due to mutations in genes regulating pancreatic beta-cell development” – This article discusses the genetic causes of congenital hyperinsulinism and the role of specific genes in regulating pancreatic beta-cell development. (PubMed)
“Congenital Hyperinsulinism” – This article provides an overview of congenital hyperinsulinism, including its clinical presentation, diagnosis, and management. It also discusses the genetic basis of the condition. (PubMed)
“Congenital hyperinsulinism: Recent advances” – This article provides a comprehensive review of the recent advances in understanding the pathophysiology, clinical features, and management of congenital hyperinsulinism. (PubMed)

These articles provide valuable scientific information about congenital hyperinsulinism, including its causes, clinical presentation, genetic basis, and management. They can be helpful for healthcare professionals, researchers, and individuals interested in learning more about this rare condition.

References

Adzick NS, et al. (2020). Congenital Hyperinsulinism. In: Kliegman RM, et al., eds. Nelson Textbook of Pediatrics. 21st ed. Philadelphia, PA: Elsevier; chap 65.
Advocate Children’s Hospital. Hyperinsulinism
ClinicalTrials.gov. Congenital Hyperinsulinism
Genetic and Rare Diseases Information Center. Congenital Hyperinsulinism
Genetic Testing Registry. Congenital Hyperinsulinism
Hussain K. (2020). Congenital Hyperinsulinism. In: Adam MP, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle
OMIM. Hyperinsulinism
PubMed. Congenital Hyperinsulinism
Shyng S-L. (Updated 2020, May 21). ABCC8-Related Hyperinsulinism. In: Adam MP, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle
Stanford Children’s Health. Congenital Hyperinsulinism