Congenital Hyperinsulinism International (CHI)

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Congenital hyperinsulinism (HI) is the most frequent cause of severe, persistent hypoglycemia in newborn babies and children. HI is a life-threatening disorder that causes dangerously low blood sugar levels. Prolonged or severe low blood sugar can cause seizures, brain damage, and even death.

Last updated 04/30/2026

Clinical

Disease Class

Channelopathies

Ciliopathies

Endocrine diseases

Epilepsy and seizure disorders

Genetic diseases

Inherited metabolic disorder

Body Systems

Digestive

Endocrine

Metabolic

Nervous / Sensory

Organs

Brain

Intestines

Kidneys

Nerves

Pancreas

Known Genetic Link

Yes, there are both genes that cause the condition and genetic factors that contribute

Causative Genes

ABCC8

AKT2

CACNA1D

EP300

FOXA2

GCK

GLUD1

HADH

HK1

HNF1A

HNF4A

KCNJ11

KDM6A

KMT2D

MAFA

PMM2

SLC16A1 (MCT1)

TRMT10A

Contributory Genes

ABCC8

AKT2

CACNA1D

CREBBP

EP300

FOXA2

GCK

GLUD1

GPC3

HADH

HK1

HNF1A

HNF4A

KCNJ11

KDM6A

KMT2D

MAFA

PMM2

SLC16A1 (MCT1)

TRMT10A

Type of Inheritance

Autosomal dominant

Autosomal recessive

De novo

Newborn Screening

Disease Mechanism(s)

Abnormal channel conductance

Abnormal channel regulation

Altered channel kinetics

Ion channel dysfunction

Mislocalization of channels

Nutrient processing disorder

Protein misfolding

Transport defect

Age of Onset

Adolescence (12-17)

Adulthood (age 18-64)

Early childhood (age 1+-5)

Infancy (age 0-1)

Middle childhood (6-11)

Average Age at Diagnosis

Infancy (age 0-1)

Life Expectancy

Adulthood (age 18-64)

Elderly (age 65+)

Infancy (age 0-1)

Affected Sex(es)

Female

Intersex

Male

National Prevalence

1001-10000

Global Prevalence

10000+

National Incidence

101-1000

Global Incidence

1001-10000

Populations and/or ancestry with higher prevalence

Yes, there are founder mutations in the Ashkenazi Jewish and Finnish population. There is a large group of affected people in Saudi Arabia. People of Turkish descent have a larger proportion of a certain type of congenital hyperinsulinism. Wherever there is more consanguinity, there is more congenital hyperinsulinism.

Symptoms / Phenotypes

behavioral changes

breathing difficulties

cardiac abnormalities

cognitive impairment / confusion / brain fog

coma

excessive hunger / hyperphagia

fatigue

feeding difficulties

hyperhidrosis

hypoglycemia

movement disorders / ataxia / tremor

muscle weakness

seizures / epilepsy

Biomarkers

Diagnostic

· glucose, insulin, ketone, genetic testing

Monitoring

· glucose, insulin, ketones

Prognostic

· genetic testing; Those who can only fast for a short time without hypoglycemia and without producing ketones have a worse prognosis.

Therapeutic

· glucose, ketones, insulin

Existing Therapies

Complementary and Alternative treatments

· maltodextrin (corn starch)

Expanded access (Compassionate Use)

Off-Label Drug Use

Regulatory Agency-Approved to Cure or Modify the Disease

· Diazoxide

Therapies in Development

Antibody-based therapy (monoclonal antibodies, biologics)

· ersodetug

Devices/medical equipment

· continuous glucose monitor

Dietary & metabolic therapies (medical food, dietary restriction, supplements, etc.)

· D20

Other (please specify)

· peptides: dasiglucagon and efpegerglucagon

Radiation therapy

· LightCure

Repurposed drug

· Diazoxide, octreotide, lanreotide,

Small molecule therapy (novel small molecule drugs)

Surgical & interventional

· Pancreatectomy

Therapeutic Development Stages

Approved/Available

Awaiting final regulatory decision

In clinical trials (Phase I, II, III, or IV)

In preclinical development

In research/exploratory phase

Therapeutic Development Role

Access to registry or natural history study

Focus group participation or coordination

Meetings with regulators (e.g., FDA listening sessions, PFDD meetings)

Outcome measures development

Recruitment and outreach to patients

Recruitment and outreach to trial sites / physicians

Results dissemination (including publications)

Study material design and/or review (not protocol) — includes patient-facing materials such as informed consent

Study protocol design and/or review (includes selection of outcome measures)

Organizational & Research

Cell Lines

iPSCs

Cell Lines, Institution

Indiana Biosciences Research Institute

Millipore

Cell Lines, Involvement

Funded

Cell Lines, share

Unsure

Disease Model

Mouse

Disease Model, Involvement

Funded

Disease Model, share

Unsure

Organizational Challenges

Yes! In drug development: 1. Companies going for other hypoglycemia disorders rather than congenital hyperinsulinism 2. Companies not prioritizing our indication 3. Companies not communicating often enough with us. On the research side, our collaborative research network is very fruitful and our research partnerships are positive and impactful.

Clinical Trial Role

Data analysis

Data sharing

Focus group

Meeting with regulators

Other consulting

Outcome measures, development

Recruitment and outreach, patients

Recruitment and outreach, trial sites/physicians

Results dissemination, publication

Study material design, review (not protocol)

Study protocol design, review

Clinical Trial Types

Observational

Phase 1

Phase 2

Phase 3

Biobank, Institution

Children’s Hospital of Philadelphia (CHOP)

Biobank, Involvement

Consulted

Center of Excellence, Institution

Charite-Universitatsmedizin

Children’s Hospital of Philadelphia (CHOP)

Collaborative Alliance on Congenital Hyperinsulinism

Cook Children’s Medical Center

Great Ormond Street Hospital (GOSH)

Northern Congenital Hyperinsulinism Service

Odense University Hospital

University Children’s Hospital Duesseldorf

Center of Excellence, Involvement

Consulted

Endorsed/Certified/Accredited

Registry

Yes, we have a registry that we created

Data Collected, Registry

Clinical data

Electronic health records/electronic medical records

Genetic data

Longitudinal natural history data

Medication usage

Patient contact info

Patient-reported data

Data Entered by, Registry

Both

Platform, Registry

Matrix

Natural History Study

Yes, we have a natural history study that we created

Data Collected, Natural History Study

Clinical endpoints (outcomes)

Electronic health records/electronic medical records

Genetic data

Medication usage

Patient-reported outcomes

Prospective data

Retrospective data

Platform, Natural History Study

Matrix

FDA Patient Listening Session

Yes

FDA Patient-Focused Drug Development (PFDD) Program

ICD Codes

We are working on obtaining an ICD-10 code

Diagnostic Guidelines

Yes, we have guidance available on our website

Yes, we have published formal guidelines in a peer-reviewed journal

In the process of developing accredited guidelines

Science Advisory Board Policies

Yes, willing to share SAB policies

Research Network Policies

Has CRN and willing to share policies

Patient Priority Survey

Research Roadmap

Yes we have a Research Roadmap, and will share policies

None

Asia

Europe

Middle East

South America

Asia

Europe

Middle East

North America

Oceania

South America