Natural History of the Hyperinsulinism Hyperammonemia Syndrome – A Multi-center Observational Study Incorporating Patient-centered Data through the HI Global Registry
Awardee: Elizabeth Rosenfeld
Institution: Children's Hospital of Philadelphia
Grant Amount: $73,045
Funding Period: February 1, 2022 - January 31, 2023
Summary:
Congenital hyperinsulinism (HI) is a rare genetic disorder that causes low blood sugar. The second most common genetic form of hyperinsulinism is the hyperinsulinism hyperammonemia (HI/HA) syndrome. Individuals with HI/HA syndrome develop low blood sugar after fasting and after eating protein-rich foods. HI/HA syndrome is also associated with high blood concentrations of ammonia, characteristic seizures, and learning and behavioral problems. Low blood sugar in HI/HA syndrome is treated with dietary modification and a medication called diazoxide, Studies have shown that the severity of low blood sugar in other (ie: non-HI/HA) forms of HI treated with diazoxide can improve with time – many individuals are able to discontinue diazoxide, or decrease the dose, as they age. There have been isolated reports documenting resolution of low blood sugar and seizures in individuals with HI/HA syndrome. However, studies describing the typical trajectory of disease over time in HI/HA syndrome are lacking. Closing this knowledge gap is an important first step toward individualizing therapy, establishing standards of care, and improving patient outcomes. We propose a multi-center, multimodal approach to describe the natural history of the HI/HA syndrome. Data will be obtained through both medical chart review and telephone interview of patients with HI/HA syndrome followed by the Hyperinsulinism Centers at the Children’s Hospital of Philadelphia and Cook Children's Health Care System. The HI Global Registry will additionally be utilized as a source for collection of detailed, patient-level data. Primary outcomes will include the frequency of diazoxide discontinuation and seizure resolution in individuals with HI/HA syndrome. The relationship between these outcomes and other assessed patient characteristics will be explored. We will also explore the utility of this multi-prong approach to examine the natural history of different HI subtypes. Ultimately, by combining clinical data and patient perspectives, we aim to develop a deeper understanding of the natural history of the HI/HA syndrome that will lead to improved patient outcomes.