This study is sponsored by Children's Hospital of Philadelphia Department of Radiology. The purpose of this research is to study 18F-L-Fluoro-DOPA (F-DOPA), a tracer, which is used to take pictures of the pancreas. This imaging test is called an F-DOPA PET scan. The F-DOPA tracer is used to highlight areas of the pancreas that make too much insulin on the PET scan images. The test includes a CT scan (computerized tomography) done at the same time on the same machine, to help define exactly where the highlighted area is located within the pancreas and determine the location of blood vessels and other vital structures. Who can participate:

• Infants, children and adults with hyperinsulinemic hypoglycemia, diagnosed by a fasting test and/or response to glucagon stimulation
• Any age, from birth on
• Requiring surgery to remove part or all of the pancreas

The purpose of the study is to evaluate blood sugar levels and beta-cell function in adolescents and adult with KATP hyperinsulinism whom did not undergo pancreatectomy. We will perform oral glucose tolerance tests, glucose potentiated arginine tests, and evaluate blood sugars in home environment by using continuous glucose monitoring for 10 days.

Our team at the Congenital Hyperinsulinism Center at CHOP is working on a research study to determine whether an experimental gene therapy product, DTX401, is safe and effective in people with glycogen storage disease type Ia (GSDIa). The FDA has not approved this drug for the treatment of GSDIa but has approved us to use this drug as part of this clinical trial. The purpose of this research study is to see if DTX401 can help people with GSDIa have normal blood sugar levels and fewer episodes of hypoglycemia. DTX041 works by delivering copies of the G6PC gene to your liver through a one-time infusion. Participation in this study will last for 2 years and will involve 30 study visits. It is possible that treatment with the study drug infusion may improve your blood sugar levels. Travel costs will be covered by the study and you will receive compensation for participating.

The purpose of this study is to look at the safety and tolerability (how well you will react) of the study drug (HM15136) and to determine if it is effective for the treatment of Congenital Hyperinsulinism (HI). HM15136 is an experimental drug which is not approved by the FDA for the treatment of HI. HM15136 is stable and has a long effect in the body, only requiring it to be given (by injection) once a week. HM15136 is designed to act like glucagon, a hormone produced by the pancreas that helps the body maintain normal blood sugar levels by increasing the glucose produced in the liver and breaking down glycogen (a form of stored glucose) into the usable glucose form.

Participation lasts for up to 22 weeks and will involve up to 13 study visits. Study procedures include taking the study drug for 8 weeks, having electrocardiograms, wearing a continuous glucose monitor (CGM) and using a handheld glucose meter, having blood and urine tests, and completing an electronic diary.

The main risks of this study include: nausea, vomiting, diarrhea, abdominal pain, injection site reactions (swelling, itching, bleeding, or pain), loss of appetite, weight loss, high blood sugar. You may benefit if the study drug proves to be more effective than your current treatment plan in treating low blood sugar.

Congenital Hyperinsulinism is the most common cause of low blood sugar (hypoglycemia) in infants and children.Infants who are born with this problem have low blood sugar, which can cause seizures or brain damage.

We are doing this study to see if the patterns of abnormalities in controlling insulin in children and adults with hyperinsulinism are related to any underlying genetic cause and to identify possible new genetic causes.This will be done by standard clinical tests of insulin control: a glucose tolerance test, a protein tolerance test, and a fasting test.

The Congenital Hyperinsulinism Center at the Childrens Hospital of Philadelphia is working on a research study to better understand how people with hyperinsulinism may have different blood sugar responses to certain tests (like fasting or drinking a high-protein shake) when compared to people without hyperinsulinism. This study will involve a screening visit where we will ask you about your medical history and any known episodes of low blood sugar. Depending on your responses during the interview, you will be asked to complete up to five tests at our outpatient research center. These tests include fasting, drinking a high-protein shake, drinking a high-sugar drink, eating a regular meal, and exercising on a stationary bike. We will collect blood samples from an IV throughout the tests to measure certain blood levels like glucose and insulin. You will be compensated for some or all of your travel costs and you will receive payment for your time. If you are interested in learning more, please contact us at HIResearch@chop.edu.

Our team is working on a study to better understand neurological problems, including seizures and developmental delays, that occur in children with hyperinsulinism, including HI/HA syndrome, and type 1 diabetes mellitus. The study involves a one-day visit to The Children's Hospital of Philadelphia and The University of Pennsylvania for a specialized magnetic resonance imaging scan (MRI) of the brain, an electroencephalogram (EEG), blood draw, and completion of questionnaires to evaluate development and behavior. The entire study visit is expected to take about five hours. If you are interested in learning more, please contact us at HIResearch@email.chop.edu.

Our team is working on a study to better understand neurological problems, including seizures and developmental delays, that occur in many individuals with HI/HA syndrome. The study involves a one day visit to The Children's Hospital of Philadelphia and The University of Pennsylvania for a specialized magnetic resonance imaging scan (MRI) of the brain, an electroencephalogram (EEG), blood draw, and completion of questionnaires to evaluate development and behavior. The entire study visit is expected to take about four hours. If you are interested in learning more, please contact us at HIResearch@email.chop.edu.

You or your child are being asked to take part in this research study because you have Glycogen Storage Disease Type III (GSD III). The purpose of this research study is to better understand blood sugar variability, muscle strength and function, and impact of Glycogen Storage Disease Type III (GSD III) on overall health. You will not receive any treatment for your GSD III as part of this study, but the information you provide will be helpful for the study sponsor, Ultragenyx Pharmaceutical Inc., to develop a new therapy for GSD III.

If you agree to take part, your participation will last for about 26 weeks and will involve up to 2 study visits to the hospital along with up to 26 phone calls. There will be no changes to your treatment regimen for GSD III as part of this study.

As a participant in the research you will:

• come to the hospital for 1-2 in person visits to complete interviews and questionnaires,
• wear a blinded continuous glucose monitor (CGM) 3 months and an unblinded CGM for 3 months,
• complete fingerstick blood sugar checks, maintain a nutrition diary for 3 or more weeks throughout the study,
• maintain a hypoglycemia symptom diary, and
• upload CGM and HHG device data to a study-provided laptop weekly.

The main risks of this study are from hypoglycemia related to your diagnosis of GSD III and a loss of confidentiality. There are no direct benefits to you for participating in this study but the information collected as part of this study will help researchers better understand GSD III.

Our team is working on a clinical drug trial that involves giving you a study drug that is not FDA-approved called RZ358. The goal of the trial is to test the study drug safety, how your body processes the drug, how the drug affects your body, and see if it can increase your blood sugar. If you agree to take part, your participation will last for up to 27 weeks and include 4 weeks of screening, 8 weeks of treatment, and a 15 week follow-up period. It is possible that treatment with the study drug infusions may improve your blood sugar levels and/or reduce the use of other medication(s) to prevent hypoglycemia. For more information, contact us at HIResearch@email.chop.edu.