glycogen storage disease I

Glycogen storage disease I (GSD I), sometimes called von Gierke disease, is an inherited metabolic disorder that interferes with the body’s ability to release glucose from stored glycogen, leading mainly to liver and blood-sugar problems. The condition results from changes in the G6PC1 gene, which encodes the enzyme glucose-6-phosphatase that works in the final step of producing free glucose during fasting. Symptoms usually begin in infancy or early childhood with episodes of low blood sugar, enlarged liver, and poor growth, though the condition can be lifelong. Exact prevalence figures are not available, but it is thought to be uncommon, and most clinicians encounter only a few individuals with GSD I in their careers. Severity and symptoms vary widely between individuals.

Early signs often appear within the first months of life when fasting tolerance is limited. Metabolic features dominate the presentation: many children experience recurrent hypoglycemia that can cause sweating, irritability, and in severe episodes seizures or even unconsciousness. Accumulation of glycogen and fat in the liver leads to a noticeably enlarged liver and the characteristic rounded "full" cheeks seen in many toddlers with GSD I. Neurological involvement is common. Persistent or severe hypoglycemia may contribute to cognitive impairment, developmental delays, and seizures. Low muscle tone (hypotonia) can further affect motor development. Families are often surprised to learn that a condition centered on sugar metabolism can also influence brain function, but the enzyme affected by G6PC1 is active in the central nervous system as well as the liver. Over time, ongoing metabolic imbalance may produce elevated blood lipids (hyperlipidemia) and uric acid (hyperuricemia). Short stature is frequent, reflecting both chronic metabolic stress and nutritional challenges. Recurrent respiratory or other infections are reported in many individuals, possibly related to altered immune function or energy reserves. Less commonly, yellowish cholesterol-rich skin nodules called xanthomas develop, especially when blood lipids remain high. Not all individuals experience every feature, and severity varies considerably. Some people maintain relatively good health with careful dietary management, while others face more significant neurological or metabolic complications.

GSD I is linked to pathogenic variants in the G6PC1 gene. G6PC1 provides instructions for making glucose-6-phosphatase, the enzyme that converts glucose-6-phosphate into free glucose in the liver and kidneys. When the enzyme is absent or works poorly, glycogen and fat build up inside cells and the body cannot release glucose efficiently during fasting, leading to low blood sugar and the other metabolic complications described above. Specific information about how the condition is inherited was not included in the available data. Because GSD I clusters in families and genetic changes can be passed from parents to children, relatives may benefit from genetic counseling to discuss testing options and family-planning considerations. Even within the same family, the course can show variable expressivity, meaning the type and severity of symptoms can differ from one affected person to another.

Currently, management focuses on supportive care and symptom management. The cornerstone of treatment is strict dietary planning to maintain steady blood glucose levels, which may include frequent meals or specialized nutritional formulas. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Monitoring usually includes periodic checks of liver and kidney function, lipid and uric acid levels, growth, and cognitive development. Because the condition affects multiple organ systems, care is typically coordinated by a multidisciplinary team that can include a metabolic specialist, dietitian, neurologist, endocrinologist, and other specialists as needed. Families should discuss individualized treatment plans and emerging therapeutic options with their healthcare team and consider genetic counseling for additional guidance.

Outcomes for individuals with GSD I depend on how early the condition is recognized, the effectiveness of metabolic control, and the presence of complications such as cognitive challenges or liver dysfunction. With attentive dietary management and regular monitoring, many children grow into adulthood, pursue education, and lead active lives. Nevertheless, some individuals may experience ongoing neurological, metabolic, or growth issues that require lifelong support. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialized metabolic clinics and patient support groups, and genetic counseling can provide guidance for relatives who may be at risk.

Several clinical trials are currently investigating new treatments such as gene-based therapies and enzyme replacement strategies aimed at correcting the underlying metabolic defect. Individuals interested in participating can search ClinicalTrials.gov or consult their care team about eligibility.