What is the difference between glucose 6 phosphatase (G6Pase) deficiency and glucose 6 phosphate dehydrogenase (G6PD) deficiency?

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From the Guidelines

Glucose 6 phosphatase (G6Pase) deficiency and glucose 6 phosphate dehydrogenase (G6PD) deficiency are two distinct genetic disorders with different clinical manifestations and management strategies, as highlighted in studies such as 1 and 1. The key difference between these two conditions lies in the metabolic pathways they affect. G6Pase deficiency, also known as glycogen storage disease type I or von Gierke disease, affects glucose production in the liver, leading to severe hypoglycemia, hepatomegaly, growth retardation, lactic acidosis, hyperlipidemia, and hyperuricemia, as noted in 1. On the other hand, G6PD deficiency is an X-linked disorder that affects red blood cells, making them vulnerable to oxidative damage and potentially triggering hemolytic anemia upon exposure to certain medications, infections, or fava beans, as discussed in 1 and 1.

Clinical Manifestations

Some of the clinical manifestations of these conditions include:

  • G6Pase deficiency: severe hypoglycemia, hepatomegaly, growth retardation, lactic acidosis, hyperlipidemia, and hyperuricemia
  • G6PD deficiency: hemolytic anemia, which can be triggered by certain medications, infections, or fava beans

Management Strategies

The management strategies for these conditions are also distinct:

  • G6Pase deficiency: treatment involves frequent feeding, cornstarch therapy, and careful dietary management to maintain blood glucose levels, as outlined in 1
  • G6PD deficiency: management involves avoiding known triggers and providing supportive care during hemolytic episodes, as discussed in 1 and 1

Pathways Affected

While both conditions involve the same molecule (glucose-6-phosphate), they affect completely different pathways:

  • G6Pase: glucose production in the liver
  • G6PD: protection of red blood cells from oxidative stress

In summary, the difference between G6Pase deficiency and G6PD deficiency lies in their distinct clinical manifestations, management strategies, and the metabolic pathways they affect, as supported by studies such as 1, 1, and 1.

From the Research

Overview of Glucose 6 Phosphatase and Glucose 6 Phosphate Dehydrogenase Deficiencies

  • Glucose 6 phosphatase (G6Pase) deficiency and glucose 6 phosphate dehydrogenase (G6PD) deficiency are two distinct metabolic disorders.
  • G6Pase deficiency, also known as glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases characterized by poor tolerance to fasting, growth retardation, and hepatomegaly resulting from accumulation of glycogen and fat in the liver 2.
  • G6PD deficiency, on the other hand, is an X-linked, hereditary genetic defect due to mutations in the G6PD gene, which cause functional variants with many biochemical and clinical phenotypes, including neonatal jaundice and acute hemolytic anemia 3, 4.

Clinical Manifestations

  • The clinical manifestations of G6Pase deficiency include hypoglycemia, hepatomegaly, growth retardation, osteopenia, and platelet dysfunctions, while G6PD deficiency is characterized by neonatal jaundice, acute hemolytic anemia, and chronic hemolysis 2, 4.
  • G6PD deficiency is usually triggered by an exogenous agent, such as certain medications or infections, while G6Pase deficiency is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia 2, 3.

Genetic and Molecular Aspects

  • G6Pase deficiency is caused by mutations in the G6PC (17q21) and SLC37A4 (11q23) genes, while G6PD deficiency is caused by mutations in the G6PD gene, with over 140 mutations described 2, 4.
  • The genetic transmission of G6Pase deficiency is autosomal recessive, while G6PD deficiency is X-linked recessive 2, 3.

Diagnosis and Management

  • The diagnosis of G6Pase deficiency is based on clinical presentation, abnormal basal values, and absence of hyperglycemic response to glucagon, while G6PD deficiency is diagnosed through screening programs and molecular analysis of the G6PD gene 2, 4.
  • The management of G6Pase deficiency involves dietary treatment to avoid hypoglycemia and acidosis, while the management of G6PD deficiency involves preventing hemolysis by avoiding oxidative stress and certain medications 2, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Glucose-6-phosphatase deficiency.

Orphanet journal of rare diseases, 2011

Research

Glucose-6-phosphate dehydrogenase deficiency.

Lancet (London, England), 2008

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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