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GM1 gangliosidosis type 2
Description
GM1 Gangliosidosis Type 2: A Rare Genetic Disorder
GM1 gangliosidosis type 2, also known as GM1G2, is a rare genetic disorder that affects the nervous system. It is characterized by slowly progressive generalized neurodegeneration and is caused by mutations in the GLB1 gene encoding the enzyme β-galactosidase.
Key Features:
- Normal Early Development: Individuals with GM1 gangliosidosis type 2 typically experience normal early development, but then undergo developmental regression [7].
- Neurodegeneration: The disorder is characterized by slowly progressive generalized neurodegeneration, which affects the brain and spinal cord [6].
- No Cherry-Red Spots: Unlike other forms of GM1 gangliosidosis, type 2 does not typically feature cherry-red spots on the skin or mucous membranes [2].
Causes and Effects:
- Genetic Mutation: GM1 gangliosidosis type 2 is caused by mutations in the GLB1 gene encoding the enzyme β-galactosidase [9].
- Nerve Cell Destruction: The disorder progressively destroys nerve cells (neurons) in the brain and spinal cord, leading to neurodegeneration [3][4].
References:
[1] - GM1 gangliosidosis type 2 is a clinically variable, infancy or childhood-onset form of GM1 gangliosidosis characterized by normal early development and ... (Source: #7) [2] - Individuals with GM1 gangliosidosis type II experience developmental regression but usually do not have cherry-red spots, coarse facial features ... (Source: #2) [3] - GM1 gangliosidosis, also called beta-galactosidase-1 deficiency, is a genetic disorder that progressively destroys nerve cells in the brain and spinal cord. (Source: #3) [4] - GM1 gangliosidosis is an inherited lysosomal storage disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. (Source: #4) [5] - GM1-gangliosidosis type II (GM1G2) is an autosomal recessive lysosomal storage disease characterized by slowly progressive generalized neurodegeneration and ... (Source: #6) [6] - GM1 gangliosidosis type 2 is a clinically variable, infancy or childhood-onset form of GM1 gangliosidosis characterized by normal early development and ... (Source: #7) [7] - Type 2 GM1 gangliosidosis consists of intermediate forms of the condition, also known as the late infantile and juvenile forms. Children with ... (Source: #8) [8] - GM1 gangliosidosis is a progressive, neurosomatic, lysosomal storage disorder caused by mutations in the GLB1 gene encoding the enzyme β-galactosidase. (Source: #9)
Additional Characteristics
- a rare genetic disorder
- autosomal recessive lysosomal storage disease
- caused by mutations in the GLB1 gene encoding the enzyme β-galactosidase
- GM1 gangliosidosis type 2
- characterized by slowly progressive generalized neurodegeneration
- typically experience normal early development, but then undergo developmental regression
- no cherry-red spots on the skin or mucous membranes
- progressively destroys nerve cells (neurons) in the brain and spinal cord
- clinically variable, infancy or childhood-onset form of GM1 gangliosidosis
Signs and Symptoms
Developmental Regression and Distinct Facial Features
Individuals with GM1 gangliosidosis type II experience developmental regression, which means they may have a delay or loss of previously acquired skills. This can manifest in various ways, such as difficulty speaking, walking, or performing daily tasks.
- Distinct facial features: Children with GM1 gangliosidosis may exhibit coarse facial features, which are a characteristic sign of this condition [4].
- No cherry-red spots: Unlike some other lysosomal storage disorders, individuals with GM1 gangliosidosis type II usually do not have cherry-red spots on their maculae (the center of the retina) [7].
These symptoms can vary in severity and may be accompanied by other signs, such as seizures, balance problems, or difficulty swallowing. It's essential to note that diagnosis is typically suggested by clinical signs, with biochemical and/or genetic tests confirming the diagnosis [2].
Additional Symptoms
- difficulty swallowing
- seizures
- difficulty walking
- balance problems
- developmental regression
- coarse facial features
- difficulty speaking
- difficulty performing daily tasks
Diagnostic Tests
Diagnostic Tests for GM1 Gangliosidosis Type 2
GM1 gangliosidosis type 2 is a genetic disorder that can be diagnosed through various tests. Here are some of the diagnostic tests used to confirm the condition:
- Biochemical and/or Genetic Tests: These tests can confirm the diagnosis by detecting the presence of the GLB1 gene mutation or measuring the enzyme activity of beta-galactosidase [2]. The tests can also identify other genetic mutations that may be associated with GM1 gangliosidosis type 2.
- Peripheral Blood Smear: This test involves examining a blood sample under a microscope to look for vacuolated lymphocytes, which are characteristic of GM1 gangliosidosis type 2 [6].
- Urine Oligosaccharides Test: This test detects the presence of abnormal oligosaccharides in the urine, which is a hallmark of GM1 gangliosidosis type 2.
- Bone Marrow Examination: This test can also be used to confirm the diagnosis by examining the bone marrow for signs of disease [6].
- Enzyme Assay: An enzyme assay can measure the activity of beta-galactosidase in the blood or other tissues, which is typically low in individuals with GM1 gangliosidosis type 2 [5].
Additional Diagnostic Tools
In addition to these tests, other diagnostic tools may also be used to monitor disease progression and assess the severity of the condition. These include:
- Inflammatory Biomarkers: Inflammatory biomarkers can be used to monitor disease progression in GM1 gangliosidosis patient serum and CSF samples [8].
- Genetic Testing Services: Some laboratories offer genetic testing services for fast, reliable diagnosis of GM1 and GM2 Gangliosidosis, including enzyme and genetic testing [4].
References
[1] Clinical resource with information about GM1 gangliosidosis type 2 and its clinical features, GLB1, available genetic tests from US and labs around the world.
[2] Diagnosis is suggested by clinical signs, such as psychomotor regression and facial coarsening. Biochemical and/or genetic tests confirm the diagnosis.
[3] Apr 26, 2023 — Individuals with GM1 gangliosidosis type II experience developmental regression but usually do not have cherry-red spots, coarse facial features are present in some cases.
[4] Our diagnostic testing services for GM1 and GM2 Gangliosidosis include enzyme and genetic testing for fast, reliable diagnosis.
[5] by R Tonin · 2019 · Cited by 15 — Current diagnostic tools for lysosomal storage diseases are based on enzymatic assays, and/or genetic screening, although glycosphingolipid (GSL) ...
[6] Sep 6, 2022 — Peripheral blood smear (testing vacuolated lymphocytes); Urine oligosaccharides; and Bone marrow examination.
[7] Diagnosis is confirmed by biochemical assay of beta-galactosidase activity and/or by molecular genetic testing. A secondary combined defect of both GLB1 and ...
[8] by R Tonin · 2019 · Cited by 15 — It has also been shown that inflammatory biomarkers are able to monitor disease progression in GM1 gangliosidosis patient serum and CSF samples.
[9] GM1 gangliosidosis, also called beta-galactosidase-1 deficiency, is a genetic disorder that progressively destroys nerve cells in the brain and spinal cord.
Additional Diagnostic Tests
- Enzyme Assay
- Bone Marrow Examination
- Peripheral Blood Smear
- or Genetic Tests
- Urine Oligosaccharides Test
- Inflammatory Biomarkers
- Genetic Testing Services
Treatment
Current Treatments for GM1 Gangliosidosis Type 2
GM1 gangliosidosis type 2 is a rare genetic disorder caused by the deficiency of the enzyme beta-galactosidase. While there are no approved therapies that can reverse the effects of this condition, several treatments have been explored to manage its symptoms.
Substrate Reduction Therapy (SRT)
One promising approach is substrate reduction therapy with Miglustat. Studies have shown that SRT can delay neurological involvement in pediatric patients with GM1 type 2 gangliosidosis [3]. This treatment works by reducing the accumulation of GM1 ganglioside in fibroblasts, which may help alleviate some symptoms.
Enzyme Replacement Therapy (ERT)
Another potential treatment is enzyme replacement therapy (ERT). ERT involves replacing the deficient enzyme with a functional one. Research suggests that ERT could be an effective treatment for GM1 gangliosidosis [2].
Stem Cell Therapy and Gene Editing
Additionally, stem cell therapy and gene editing have been proposed as potential treatments for GM1 gangliosidosis. These approaches aim to replace or correct the faulty gene responsible for the condition.
Current Challenges
Despite these promising treatments, there are currently no approved therapies that can reverse the effects of GM1 gangliosidosis type 2. Current approaches focus on managing symptoms through interdisciplinary collaboration [4].
Gene Therapy in Clinical Trials
A recent development is the initiation of clinical trials for a gene therapy called AXO-AAV-GM1. This treatment has the potential to provide meaningful clinical benefits for patients with GM1 gangliosidosis [7].
References:
[2] by D Foster · 2024 · Cited by 3 — The most promising treatments for GM1, include enzyme replacement therapy (ERT), substrate reduction therapy (SRT), stem cell therapy and gene editing.
[3] by ER Nicoli · 2021 · Cited by 59 — Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: a multicenter experience.
[4] by AK Rha · 2021 · Cited by 51 — 17,18 Patients with GM1 often receive anti-convulsants to control seizures, gastrostomy tubes to ensure proper nutrition and hydration, and ...
[7] Oct 16, 2020 — “AXO-AAV-GM1 is the first gene therapy to enter clinical trials for GM1 gangliosidosis and has the potential to provide meaningful clinical ...
Recommended Medications
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Differential Diagnosis
Differential Diagnosis of GM1 Gangliosidosis Type 2
GM1 gangliosidosis type 2 is a rare lysosomal storage disorder that can be challenging to diagnose due to its similarity with other conditions. The differential diagnosis for GM1 gangliosidosis type 2 includes:
- Mucopolysaccharidoses: A group of genetic disorders caused by the deficiency of enzymes needed to break down and recycle sugar molecules in the body.
- Sphingolipidoses: A group of genetic disorders caused by the deficiency of enzymes needed to break down sphingolipids, a type of fat molecule found in cell membranes.
- Oligosaccharidoses: A group of genetic disorders caused by the deficiency of enzymes needed to break down oligosaccharides, a type of sugar molecule.
Other conditions that may be considered in the differential diagnosis of GM1 gangliosidosis type 2 include:
- Spinocerebellar ataxia syndromes: A group of genetic disorders that affect the cerebellum and spinal cord, leading to problems with coordination and balance.
- Gaucher disease type 3: A rare form of Gaucher disease that affects the nervous system and causes progressive neurodegeneration.
- Canavan disease: A rare genetic disorder that affects the brain and causes progressive neurodegeneration.
- Sialidosis type II: A rare genetic disorder caused by the deficiency of the enzyme sialidase, which is needed to break down sialic acid in the body.
- Infantile Alexander's disease: A rare genetic disorder that affects the brain and causes progressive neurodegeneration.
- Ceroid lipofuscinoses: A group of genetic disorders caused by the accumulation of abnormal proteins and lipids in cells, leading to progressive neurodegeneration.
These conditions can be difficult to distinguish from GM1 gangliosidosis type 2 based on clinical presentation alone. Therefore, a comprehensive diagnostic workup, including genetic testing, is essential for accurate diagnosis and management.
References:
- [3] Rapidly progressive neurodegenerative disorders such as Gaucher disease type 3, GM1 gangliosidoses type 2, Canavan disease, sialidosis type II, infantile Alexander’s disease, ceroid lipofuscinoses, Juvenile Niemann-Pick C (NPC), and early-onset spinocerebellar ataxia, among others, should be considered in the differential diagnoses of GM1 gangliosidosis type 2.
- [13] Rapidly progressive neurodegenerative disorders such as Gaucher disease type 3, GM1 gangliosidoses type 2, Canavan disease, sialidosis type II, infantile Alexander’s disease, ceroid lipofuscinoses, Juvenile Niemann-Pick C (NPC), and early-onset spinocerebellar ataxia, among others, should be considered in the differential diagnoses of GM1 gangliosidosis type 2.
Additional Differential Diagnoses
- Spinocerebellar ataxia syndromes
- Mucopolysaccharidoses
- Gaucher disease type 3
- Sphingolipidoses
- Oligosaccharidoses
- Sialidosis type II
- Infantile Alexander's disease
- Ceroid lipofuscinoses
- Canavan disease
Additional Information
- rdf-schema#domain
- https://w3id.org/def/predibionto#has_symptom_3375
- owl#annotatedSource
- t354002
- oboInOwl#hasOBONamespace
- disease_ontology
- oboInOwl#id
- DOID:0080501
- core#notation
- DOID:0080501
- oboInOwl#hasDbXref
- MIM:230600
- IAO_0000115
- A GM1 gangliosidosis that is characterized by slowly progressive generalized neurodegeneration and mild skeletal changes, with onset between 7 months and 3 years of age.
- rdf-schema#label
- GM1 gangliosidosis type 2
- oboInOwl#hasExactSynonym
- juvenile GM1 gangliosidosis
- rdf-schema#subClassOf
- http://purl.obolibrary.org/obo/DOID_3322
- 22-rdf-syntax-ns#type
- http://www.w3.org/2002/07/owl#Class
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