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 May 2024

Clinical

Disease Class

Rare abdominal surgical diseases

Rare endocrine diseases

Rare gastroenterological diseases

Rare genetic diseases

Rare inborn errors of metabolism

Rare neurological diseases

Body Systems

Digestive

Endocrine

Metabolic

Nervous / Sensory

Organs

Brain

Intestines

Kidneys

Pancreas

Genes

ABCC8

CACNA1D

CREBBP

EP300

FOXA2

GCK

GLUD1

GPC3

HADH

HK1

HNF1A

HNF4A

KCNJ11

KDM6A

KMT2D

MAFA

PMM2

SLC16A1 (MCT1)

TRMT10A

Type of Inheritance

Not specified / unknown

Disease Mechanism(s)

Abnormal cell proliferation

Enzyme deficiency

Epigenetic aberration

Glutamate pathway malfunction

Glycogen pathway dysregulation

Glycosylation disorder

Inborn errors of metabolism

Insulin pathway defects

Ion channel dysfunction

Pathogenic mutation

Protein misfolding

mTOR pathways dysregulation

Age of Onset

Early childhood (age 1+-5)

Infancy (age 0-1)

Prebirth

Incidence

Less than 10

Prevalence

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

cardiac abnormalities

cognitive impairment / confusion / brain fog

coma

excessive hunger / hyperphagia

feeding difficulties

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

Alternative treatments (eg. nutritional supplements)

· maltodextrin (corn starch)

Drugs approved for the disease(s)

Drugs used off-label

· octreotide, octreotide LAR, lanreotide, Dextrose, glucagon

Expanded access to drugs

· Dasiglucagon, RZ358

Organizational & Research

Cell Lines

Beta cells

Rat Insulinoma Cell Line

Cell Lines, location

Millipore

Cell Lines, share

Disease Model

Mouse

Disease Model, location

AscendRare Pharmaceutical Technology

Childrens Hospital at Vanderbilt

Children’s Hospital of Philadelphia (CHOP)

Stanford University

Washington University

Disease Model, share

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

Biobank

Children’s Hospital of Philadelphia (CHOP)

Center of Excellence

Charite-Universitatsmedizin

Children’s Hospital of Philadelphia (CHOP)

Cook Children’s Medical Center

Great Ormond Street Hospital (GOSH)

University Children’s Hospital Duesseldorf

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 use an ICD-10 code capturing the family of diseases to which our disease belongs

Diagnostic Guidelines

Yes

Clinical/Treatment Guidelines

Yes

Organizational Roles

Director of Operations/Director of Development

Executive Director

Patient Engagement Manager/Director

Registry Coordinator

Research/Scientific Director

Science Advisory Board Policies

Yes, willing to share SAB policies

Research Network Policies

Has CRN and willing to share policies

Research Roadmap

Yes we have a Research Roadmap, and will share policies

International Chapters

None

International Partners

Asia

Europe

Middle East

South America