Glycogen Storage Disease Type I

In children with a glycogen storage disorder, one of the enzymes needed to convert glucose into glycogen, or to break down glycogen into glucose, is missing. There are many different types of glycogen storage disorders (also known as glycogenoses). Type 1 glycogenosis results in low blood sugar (hypoglycemia), increased lactate (a glucose metabolite produced by body tissues when oxygen supply is insufficient) and a bulky abdomen (glycogen accumulation induces liver enlargement). Low blood sugar leads to sweating, confusion, convulsions and coma. Type 1 glycogenosis manifests itself early in life. In children, glycogen storage disorders can have other consequences, such as stunted growth linked to chronic acidosis, tend to increase uric acid levels (a breakdown product) which accumulate in the joints, leading to gout, and in the kidneys, leading to kidney stones. The mainstay of treatment is frequent oral feeding with raw cornstarch or a lactose-free preparation with maltodextrin to maintain normal blood sugar levels. Nocturnal enteral feeding via gastrostomy is necessary during the first years of life. These children tend to have greater insulin reactions (= hormone that brings sugar into the cells), resulting in a more rapid fall in blood sugar levels. Diazoxide is a drug that inhibits pancreatic insulin secretion and prevents blood sugar levels from falling. It has been used successfully in some patients. The main objective of this project is to describe the metabolic balance in children with type 1 glycogenosis treated with Diazoxide compared with children who did not receive Diazoxide treatment.

The aim of this observational study is to evaluate the impact of raw cornstarch supplementation on postprandial glycemic response in adult patients with Glycogen Storage Disease type I (GSD I), using continuous glucose monitoring (CGM) systems.GSD I is a rare inherited metabolic disorder characterized by impaired glucose homeostasis during fasting, leading to recurrent hypoglycemia and metabolic abnormalities. Nutritional therapy, based on frequent carbohydrate intake and raw cornstarch supplementation, represents the cornerstone of treatment. However, the optimal timing of raw cornstarch administration in relation to meals and its effect on postprandial glycemic control remain unclear.The main question this study aims to answer is: "Does raw cornstarch intake during meals affect postprandial glycemic response in adult patients with Glycogen Storage Disease type I?". Additional objectives include evaluating whether dose and timing of cornstarch intake influences glucose profile, glycemic variability, hypoglycemic events, body composition, energy expenditure, and lipid profile. Participants will include adults with genetically confirmed GSD Ia or Ib who routinely use CGM systems and regularly consume raw cornstarch as part of their dietary management. This is a real-life observational study, and participants will continue their routine clinical care without receiving additional experimental treatments. After providing informed consent, participants will undergo clinical, metabolic, and nutritional assessments, including: * anthropometric measurements; * body composition analysis by bioelectrical impedance; * indirect calorimetry for resting energy expenditure; * handgrip strength evaluation; * biochemical analyses, including fasting glucose, HbA1c, lipid profile, liver enzymes, creatinine, uric acid, and lactate. CGM-derived parameters collected during the 14 days preceding the visit will be analyzed, including Time in Range (TIR), Time Above Range (TAR), Time Below Range (TBR), coefficient of variation (CV%), Glucose Management Indicator (GMI), and frequency of hypoglycemic episodes. Participants will also complete a 7-day food diary reporting meal timing, food intake, and raw cornstarch consumption. Investigators will compare meals consumed with and without raw cornstarch supplementation and evaluate postprandial glycemic trends. Postprandial glycemic response will be assessed using dynamic indices, including glucose peak, nadir, time to peak, time to nadir, glucose excursion rates, and incremental area under the curve (iAUC). Glucose values will be analyzed every 5 minutes for up to 4 hours after meals using CGM data. Inclusion criteria include: genetically confirmed GSD Ia or Ib, age \>18 years, routine CGM use, and habitual raw cornstarch consumption.Exclusion criteria include psychiatric disorders, pregnancy, celiac disease, dialysis treatment, nocturnal enteral feeding, and severe acute or chronic illnesses. Approximately 8 adult patients are expected to be enrolled. Risks for participants are considered minimal, as all procedures are part of routine clinical follow-up. Potential benefits include improved personalization of nutritional therapy and optimization of carbohydrate and raw cornstarch administration, potentially improving glycemic control and reducing metabolic complications in patients with GSD I.

The goal of this study is to determine if the Lactate Plus meter is accurate compared to lab lactate levels, and to determine if the Accu chek guide glucometer is accurate compared to lab serum glucose levels in patients with Glycogen Storage Disease Types Ia, Ib and XI. To determine this, patient's will have a one-time planned admission to Connecticut Children's for approximately 8 hours and receive hourly blood draws as well as finger-sticks.

The present project will specifically assess metabolic effects of dietary interventions with controlled intake of fructose and fructose/galactose in GSDI, with the aim to provide evidence whether relaxed dietary restrictions of fructose and galactose may be justified in treatment recommendations at least for adults, which would considerably enlarge food choice in everyday life of the patients with an expected positive impact on the quality of life of patients with this rare disorder.