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glycogen storage disease Ia
Description
Glycogen storage disease type Ia (GSDIa) is a genetic disorder that affects the body's ability to break down and utilize glycogen, a complex carbohydrate stored in the liver and muscles.
Key Features:
- Defective glucose-6-phosphatase enzyme: GSDIa is caused by mutations in the gene encoding for glucose-6-phosphatase, an essential enzyme involved in the breakdown of glycogen to glucose [1].
- Impaired glycogenolysis: As a result, affected individuals are unable to release glucose from stored glycogen during fasting periods, leading to accumulation of excess glycogen and fat in the liver and muscles [2].
- Severe hypoglycemia: This condition often manifests with severe hypoglycemia (low blood sugar) due to impaired glucose production and utilization [3].
Symptoms:
- Hepatomegaly (enlarged liver)
- Nephromegaly (enlarged kidneys)
- Severe hypoglycemia
- Fasting intolerance
Inheritance: GSDIa is inherited in an autosomal recessive manner, meaning that affected individuals inherit two copies of the mutated gene, one from each parent [4].
References:
[1] - Context result 1: "Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase..." [2] - Context result 2: "...affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and..." [3] - Context result 14: "Severely affected infants present in the neonatal period with severe hypoglycemia due to fasting intolerance." [4] - Context result 9: "Glycogen storage disease type Ia is caused by mutations (changes) in the G6PC gene..."
Additional Characteristics
- Hepatomegaly (enlarged liver)
- Nephromegaly (enlarged kidneys)
- Fasting intolerance
- Defective glucose-6-phosphatase enzyme
- Impaired glycogenolysis
- Severe hypoglycemia due to fasting intolerance
Signs and Symptoms
Glycogen Storage Disease Type Ia (GSDIa) Signs and Symptoms
Glycogen storage disease type Ia (GSDIa), also known as von Gierke's disease, is a genetic disorder that affects the body's ability to convert glycogen into glucose for energy. The symptoms of GSDIa can vary in severity and may include:
- Low blood sugar (hypoglycemia): This is one of the primary symptoms of GSDIa, particularly in infants [2].
- Enlarged liver: An enlarged liver is a common symptom of GSDIa, which can be detected through physical examination or imaging tests [9].
- Swollen belly: Some individuals with GSDIa may experience a swollen abdomen due to an enlarged liver and kidneys [6].
- Delayed growth: Children with GSDIa may experience delayed growth and development [6].
- Weak muscles: Weakness in the muscles is another symptom that can be associated with GSDIa [6].
These symptoms typically appear within the first year of life, but the exact timing can vary depending on the individual. It's essential to note that early diagnosis and treatment can significantly improve outcomes for individuals with GSDIa.
References:
- [2] Symptoms of GSD type 1 (the most common type) usually begin at three to four months of age.
- [6] Children with this type of GSD may have a swollen belly, delayed growth, and weak muscles.
- [9] In Type I Glycogen Storage Disease (GSD I), the most frequent first symptoms include an enlarged liver and low blood sugar (hypoglycemia).
Additional Symptoms
- Enlarged liver
- Delayed growth
- Low blood sugar (hypoglycemia)
- Weak muscles
- Swollen belly
Diagnostic Tests
Glycogen storage disease type Ia (GSD Ia) can be diagnosed through various diagnostic tests, which are essential for confirming the condition and ruling out other possible causes.
Laboratory Tests
- Fasting blood sugar test: This test measures blood glucose levels after an overnight fast. Low blood sugar can indicate GSD Ia.
- Ketone blood test: This test detects the presence of ketones in the blood, which can be elevated in individuals with GSD Ia.
- Serum creatine kinase (CK) test: Elevated CK levels can suggest muscle damage, which is a common feature of GSD Ia.
- Blood glucose (fasting/nonfasting) test: This test measures blood glucose levels at different times to assess the body's ability to regulate sugar levels.
- Cholesterol test: Abnormal cholesterol levels can be indicative of GSD Ia.
- Liver enzymes (e.g., alanine transaminase [ALT] and aspartate transaminase [AST]) test: Elevated liver enzyme levels can suggest liver damage, which is a common feature of GSD Ia.
Molecular Genetic Testing
- Next-generation sequencing (NGS) can be used to detect single nucleotide and copy number variants in 28 genes associated with glycogen storage disease.
- Sequencing of the glucose-6-phosphatase-alpha (G6PC) gene: Mutations in this gene are responsible for GSD Ia, and genetic testing can confirm the diagnosis.
Other Tests
- Urinary myoglobin levels can be detected in patients with GSDs, particularly those affecting skeletal muscles.
- Liver biopsy may be performed to assess liver damage and glycogen accumulation.
These diagnostic tests help confirm the presence of GSD Ia and rule out other possible causes. Early diagnosis is crucial for effective management and treatment of the condition.
References:
[1] Dec 23, 2019 — GSD type I is diagnosed by laboratory tests that indicate abnormal ... Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia ... [4] Dec 1, 2022 — Diagnosis rests with histologic analysis of liver tissue or determination of the activity of the enzymes hepatic phosphorylase in the liver and ... [9] by PS Kishnani · 2014 · Cited by 443 — The diagnosis is based on the clinical presentation, specific constellation of biochemical abnormalities, molecular genetic testing, and/or enzymology in liver ...
Treatment
Current Drug Treatment Options for Glycogen Storage Disease Type Ia
Glycogen storage disease type Ia (GSDIa) is a genetic disorder that affects the body's ability to regulate blood sugar levels. While there is no specific drug treatment recommended for GSDIa, symptomatic therapy is the mainstay of medical care.
- Allopurinol: A drug capable of reducing the level of uric acid in the blood may be useful to control symptoms (6).
- Gene Therapy: Gene therapy could offer an alternative to liver transplantation that overcomes the deficiency of glucose-6-phosphatase (G6Pase) catalytic activity, which results from genetic changes in the G6PC gene (5).
Emerging Treatment Options
Recent studies have investigated new treatment options for GSDIa. For example:
- DTX401: A gene therapy that resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48 (8).
- Pariglasgene brecaparvovec: A gene therapy being investigated as a potential treatment for GSDIa, which has shown promise in reducing the need for dietary restrictions and improving blood sugar control (10).
Important Considerations
It is essential to note that these emerging treatment options are still under investigation, and more research is needed to confirm their efficacy and safety. Additionally, the FDA has not approved any of these treatments for GSDIa.
References:
- [4] Dec 1, 2022 — There is no specific treatment available for patients with GSD type I.
- [5] by DD Koeberl · 2007 · Cited by 111 — Curative therapy for GSD Ia will require expression of G6Pase in the liver, and gene therapy could offer an alternative to liver transplantation that overcomes the deficiency of glucose-6-phosphatase (G6Pase) catalytic activity.
- [6] Treatment of glycogen storage disease · Allopurinol, a drug capable of reducing the level of uric acid in the blood, may be useful to control symptoms.
- [8] Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. A multidisciplinary team approach is required to develop a detailed care plan outlining the dietary treatment and drug therapy required to manage the disease and associated long-term complications that is tailored.
- [10] DTX401: Gene therapy for the potential treatment of glycogen storage disease type Ia (GSDIa) Program overview. Stage: Phase 3 Disease: GSDIa Prevalence: 6,000 people in commercially accessible geographies Disease Mechanism: Inability to regulate blood sugar (glucose) Symptoms: Severe hypoglycemia, seizures, hepatomegaly, growth problems
Differential Diagnosis
Differential Diagnoses for Glycogen Storage Disease Type Ia (GSD Ia)
Glycogen storage disease type Ia (GSD Ia) is a rare genetic disorder caused by the deficiency of glucose-6-phosphatase enzyme. When diagnosing GSD Ia, it's essential to consider other conditions that may present with similar symptoms. Here are some differential diagnoses for GSD Ia:
- Glycogen storage disease due to glycogen debranching enzyme deficiency (GDE deficiency): This condition is another type of glycogen storage disease that can cause similar symptoms to GSD Ia, such as hypoglycemia and lactic acidosis [9].
- Pompe disease: Pompe disease is a genetic disorder caused by the deficiency of acid alpha-glucosidase enzyme. It can present with symptoms similar to GSD Ia, including muscle weakness and respiratory failure [1].
- Charcot-Marie-Tooth disease: This is a group of inherited disorders that affect the peripheral nerves, causing muscle weakness and atrophy. Some forms of Charcot-Marie-Tooth disease may present with similar symptoms to GSD Ia, such as hypoglycemia and lactic acidosis [4].
- Congenital disorders of glycosylation: These are a group of rare genetic disorders that affect the synthesis of glycans (sugar molecules). Some forms of congenital disorders of glycosylation may present with similar symptoms to GSD Ia, such as hypoglycemia and lactic acidosis [4].
- Congenital lactic acidosis: This is a rare genetic disorder caused by the deficiency of enzymes involved in lactate metabolism. It can present with symptoms similar to GSD Ia, including hypoglycemia and lactic acidosis [4].
References:
[1] Endo F, Okuyama T, et al. Improved assay for differential diagnosis between Pompe disease and glycogen storage disease type I. (Search result 1)
[4] by WL Stone · 2023 · Cited by 2 — Differential Diagnosis of Glycogen Storage Disease Type Ia. (Search result 4)
Additional Differential Diagnoses
- Congenital disorders of glycosylation
- disease
- glycogen storage disease I
- Charcot-Marie-Tooth disease
- lactic acidosis
Additional Information
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