glycogen storage disease Ib

Glycogen Storage Disease Type Ib (GSDIb), also known as von Gierke disease, is a rare inherited disorder caused by mutations in the SLC37A4 gene. This genetic mutation leads to a deficiency of glucose-6-phosphate translocase, an enzyme responsible for transporting glucose-6-phosphate across the membrane of cells.

As a result of this deficiency, the body's ability to break down glycogen and release glucose into the bloodstream is impaired. This can lead to various symptoms and complications, including:

• Hepatomegaly: Enlargement of the liver due to accumulation of glycogen.
• Growth retardation: Slowed growth and development in children.
• Muscle weakness: Weakness and fatigue in muscles due to lack of glucose availability.
• Cardiac involvement: Cardiac problems, such as arrhythmias and cardiomyopathy.

There are two main subtypes of GSDIb: Type Ia and Type Ib. Type Ia is caused by a deficiency in the enzyme glucose-6-phosphatase, while Type Ib is caused by a deficiency in the transport protein glucose-6-phosphate translocase [5][10]. Both deficiencies affect the body's ability to break down glycogen and release glucose into the bloodstream.

GSDIb is an autosomal recessive disorder, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition. The disease presents with variable cardiac muscle, skeletal muscle, and liver involvement [1].

References:

[1] November 13, 2021 - It is an autosomal recessive disorder in which there is an AGL gene mutations which causes deficiency in glycogen debranchinging enzyme and limited storage of dextrin. The disease presents with variable cardiac muscle, skeletal muscle and liver involvement and has different subtypes.

[5] October 11, 2024 - GSD Ia is caused by a deficiency in the enzyme glucose-6-phosphatase; GSD Ib, a deficiency in the transport protein glucose-6-phosphate translocase. Because glycogenolysis is the principal metabolic mechanism by which the liver supplies glucose to the body during fasting, both deficiencies ...

[10] by J Schaub · 1983 · Cited by 59 — Glycogen storage disease type Ib has all the clinical manifestations of glycogen storage disease type Ia such as hepatomegaly, growth retardation, ...

Glycogen storage disease type Ib (GSD Ib) is a rare genetic disorder that affects the body's ability to break down glycogen, a complex carbohydrate stored in the liver and muscles.

Common Signs and Symptoms:

• Hypoglycemia: Low blood sugar levels due to impaired glucose production from glycogen breakdown.
• Liver enlargement (hepatomegaly): The liver becomes enlarged due to excessive accumulation of glycogen.
• Kidney enlargement (nephromegaly): The kidneys become enlarged due to the buildup of glycogen and other substances.
• Growth retardation: Children with GSD Ib may experience delayed growth and development.
• Lactic acidemia: Elevated levels of lactic acid in the blood, which can lead to fatigue, weakness, and shortness of breath.
• Hyperlipidemia: High levels of lipids (fats) in the blood, which can increase the risk of heart disease.
• Hyperuricemia: Elevated levels of uric acid in the blood, which can increase the risk of kidney stones.

Other Symptoms:

• Neutropenia and neutrophil dysfunction: Patients with GSD Ib may experience low white blood cell counts (neutropenia) and impaired function of these cells.
• Increased susceptibility to infections: The compromised immune system makes patients more susceptible to infections.
• Fatigue and weakness: Recurring episodes of hypoglycemia can lead to fatigue, weakness, and shortness of breath.

Age of Onset:

• Symptoms typically appear around 3-4 months of age, but can vary depending on the severity of the disease.

It's essential to note that these symptoms may not be present in all individuals with GSD Ib, and the severity of the disease can vary widely among affected people.

Glycogen storage disease type Ib (GSDIb) can be diagnosed through various laboratory tests that indicate abnormal levels of glucose and glycogen in the body.

• Fasting blood sugar test: This test measures blood sugar levels after an overnight fast, which can point to GSDIb if they are low [4].
• Ketone blood test: This test checks for the presence of ketones in the blood, which can indicate that the body is breaking down fat for energy instead of glucose [4].
• Molecular genetic testing: This involves sequencing the full genes associated with GSDIb, such as G6PC and SLC37A4, to confirm the diagnosis [3].
• Blood tests: These tests check blood glucose levels and how the liver, kidneys, and muscles are functioning, which can indicate abnormal glycogen metabolism [2].

In addition to these tests, a diagnosis of GSDIb may also be supported by:

• Abnormal liver function tests: These tests can indicate that the liver is not functioning properly due to abnormal glycogen storage [2].
• Neutropenia: Many people with GSDIb have a shortage of white blood cells (neutropenia), which can make them prone to recurrent bacterial infections [8].

It's worth noting that a diagnosis of GSDIb typically involves a combination of these tests, as well as a thorough medical history and physical examination.

References: [1] Not applicable [2] 2. Diagnosis of glycogen storage disease · blood tests to check blood glucose levels and how the liver, kidneys and muscles are functioning · abdominal ultrasound to ... [3] by Z Beyzaei · 2019 · Cited by 30 — Molecular genetic testing via sequencing of the G6PC (GSD Ia) and SLC37A4 (GSD Ib) full genes can be used for confirming the diagnosis of these diseases ... [4] How is glycogen storage disease diagnosed? · Fasting blood sugar test: Fasting low blood sugar can point to GSD. · Ketone blood test: Your body produces ketones ... [5] Not applicable [6] by WL Stone · 2023 · Cited by 33 — Glycogen storage diseases (GSDs) are inherited inborn errors of carbohydrate metabolism. Clinical onset can range from neonatal life to adulthood. [7] Dec 23, 2019 — This type of GSDI is termed glycogen storage disease type Ib. ... GSD type I is diagnosed by laboratory tests that indicate abnormal ... [8] Jul 1, 2015 — Many people with GSDIb have a shortage of white blood cells (neutropenia), which can make them prone to recurrent bacterial infections. [9] Not applicable [10] Not applicable

Treatment Options for Glycogen Storage Disease Ib

Glycogen storage disease Ib (GSD Ib) is a rare genetic disorder that affects the body's ability to break down glycogen, leading to various complications. While there is no specific treatment available for GSD Ib, several management strategies can help alleviate symptoms and improve quality of life.

• Dietary Management: Individuals with GSD Ib require careful monitoring of their diet, including the frequency of meals and type of foods eaten [4]. A balanced diet that is rich in protein, moderate in carbohydrates, and low in fat can help manage symptoms.
• Symptomatic Therapy: As there is no specific treatment available for GSD Ib, symptomatic therapy is the mainstay of medical care [3]. This includes managing complications such as neutropenia/neutrophil dysfunction, chronic inflammatory bowel disease, and other related conditions.
• Empagliflozin: Recent studies have explored the potential use of empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in treating GSD Ib [7][9]. Empagliflozin may be a new safe treatment option for patients with advanced stages of the disease.

Gene Therapy and Other Experimental Treatments

• Gene Therapy: Researchers are exploring gene therapy as a potential treatment for GSD Ib. This involves using adeno-associated virus (AAV) vectors to deliver the glucose-6-phosphatase gene to affected individuals [8].
• Colony-Stimulating Factors: Colony-stimulating factors have been used to treat chronic inflammatory bowel disease in patients with GSD Ib [6].

Importance of Ongoing Research

While these treatment options show promise, more research is needed to fully understand the efficacy and safety of these approaches. Ongoing studies will help determine the best course of management for individuals with GSD Ib.

References:

[3] Dec 1, 2022 — There is no specific treatment available for patients with GSD type I. [4] The treatment of GSDIb involves careful monitoring of the affected individual's diet... [7] by J Bidiuk · 2022 · Cited by 14 — Empagliflozin may be new safe treatment in GSD Ib patients with advanced stage of the disease. [8] by MA Chen · 2016 · Cited by 98 — Gene therapy using AAV-8 injected into the diaphragm is also being attempted in humans with the disease [59]. [9] by SC Grünert · 2023 · Cited by 14 — The use of SGLT2 inhibitors is a breakthrough in the therapy of GSD Ib, and empagliflozin has the potential to become the first-line treatment.

Differential Diagnoses for Glycogen Storage Disease Ib

Glycogen storage disease Ib (GSD Ib) is a rare genetic disorder that affects the body's ability to break down glycogen, leading to excessive accumulation in the liver and kidneys. When diagnosing GSD Ib, it's essential to consider other conditions that may present with similar symptoms. Here are some differential diagnoses for GSD Ib:

• Other Glycogenoses: Disorders of glycogen metabolism, such as glycogen storage disease due to glycogen debranching enzyme deficiency (GDE deficiency), can mimic the symptoms of GSD Ib [9].
• Glucose-6-phosphatase Deficiency: A deficiency in glucose-6-phosphatase enzyme (GSD Ia) or a deficiency in the microsomal transport proteins for glucose 6-phosphate (GSD Ib) can result in excessive accumulation of glycogen and fat in the liver, kidney, and other organs [15].
• Congenital Lactic Acidosis: This condition is characterized by an accumulation of lactic acid in the blood, which can be a feature of GSD Ib [3].

Key Features to Consider

When considering differential diagnoses for GSD Ib, physicians should look out for the following key features:

• Fasting Hypoglycemia: Low blood glucose levels during fasting periods are a hallmark of GSD Ib.
• Hepatomegaly: An enlarged liver can be a feature of GSD Ib due to excessive glycogen accumulation.
• Hypertransaminasemia: Elevated liver enzymes can indicate liver damage or dysfunction, which is common in GSD Ib.

Diagnostic Considerations

In diagnosing GSD Ib, physicians should consider the following diagnostic approaches:

• Molecular Genetic Testing: Full gene sequencing of the G6PC1 (GSD Ia) and SLC37A4 (GSD Ib) genes can confirm the diagnosis [10].
• Hepatic Enzyme Activity Analysis: This test can measure glucose-6-phosphatase catalytic activity, which is specific to GSD Ia [11].

References

[9] Differential diagnoses include the other glycogenoses, in particular glycogen storage disease due to glycogen debranching enzyme deficiency (GDE deficiency) or ...

[15] Glycogen storage disease type I (GSD I) is a rare disease of variable clinical severity that primarily affects the liver and kidney. ... and severity. In addition, patients with type Ib have ...