Clinical Survey Study to Assess Physical Function and the Incidence of Hypoglycemia in Patients 1 Year of Age and Over with GSD III.

Glycogen Storage Diseases represent a group of metabolic disorders in which
there is a deficiency in the function of enzymes required to metabolize
glycogen, including synthesis, degradation, or regulation of glycogen. Glycogen
is the stored form of glucose, with glycogen formation occurring with
carbohydrate loading and glycogen degradation (glycogenolysis) to glucose
occurring to provide immediate energy and maintain blood glucose levels. GSD
III is a rare, autosomal recessive, metabolic disease, characterized by a broad
spectrum of clinical manifestations affecting primarily the liver, cardiac
muscle, and skeletal muscle. Other names for GSD III include limit dextrinosis
disease, Cori disease, and Forbes disease.

Clinical characteristics vary depending on the relative extent of liver or
muscle involvement, with most patients experiencing consequences of both liver
and muscle involvement . Patients with GSD III generally present by the age of
1.5 years with hepatomegaly, the most common presenting clinical sign. Other
hallmarks of the disease include ketotic hypoglycemia with fasting,
hyperlipidemia, growth retardation, elevated liver transaminases, and elevated
creatine kinase. Some individuals also develop osteoporosis or osteopenia over
time . Hepatomegaly may appear to improve with age with a reduced relative
glucose requirement; however, it is increasingly recognized that progressive
liver cirrhosis and hepatic failure can occur, with some patients developing
hepatic adenoma, hepatocellular carcinoma, or end-stage liver cirrhosis .
Skeletal and cardiac muscle involvement also varies widely, with reports of
asymptomatic cardiomyopathy, symptomatic cardiomyopathy leading to death,
ventricular hypertrophy, sudden death due to cardiac arrhythmia, and slowly
progressing myopathy with distal, proximal or generalized myopathy.

Currently, there is no approved treatment for GSD III, and symptoms are managed
with nutrition intervention, including small, frequent feedings and cornstarch
to avoid hypoglycemia in children, a high protein diet, low complex
carbohydrates, avoidance of fasting, and avoidance of simple sugars. Current
nutrition management is focused on prevention of hypoglycemia and maintenance
of glucose levels. Case reports indicate that a strict ketogenic regimen may
reduce hypertrophic cardiomyopathy .
No specific management approach has been shown to address the progressive and
debilitating muscle impairment experienced by patients with GSD III. The
current treatment approach of nutrition management is supportive, but
incomplete, and highlights a need for a targeted therapy that replaces the
missing or defective enzyme.

The primary objective of this study is to evaluate the incidence of
hypoglycemia in adult and pediatric patients with GSD III.

The secondary objective of this study is to evaluate the sensitivity of various
muscle strength and function measures to detect deficits in patients with
Glycogen Storage Disease (GSD) III.

This is a non-interventional clinical survey study in patients >= 1 year of age
with GSD III

No investigational product (IP) or reference product will be administered as
part of this study.
The burden associated with participation in this study is the time taken to
complete study assessments, the travel taken for any onsite visits, and
potential for mild discomfort from participating in procedures and assessments,
including discomfort and local skin irritation from
the continuous glucose monitor (CGM) and finger sticks for handheld glucometer
(HHG).
Patients may directly benefit by having previously undetected disease
manifestations, including asymptomatic hypoglycemia, identified during the
study assessments. This may lead to improved dietary management.
With no treatments currently available for this disorder, a clear medical need
exists for a novel therapeutic that could alter the clinical course of the
disease. This study is being conducted to support the clinical development of a
novel therapy for GSD III. In participating, subjects may
indirectly benefit by contributing to the understanding of GSD III and the
development of new therapies.