Rare Rheumatology News

Disease Profile

GM1 gangliosidosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Childhood

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ICD-10

E75.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Beta galactosidase 1 deficiency; GLB 1 deficiency; Beta-galactosidosis

Summary

GM1 gangliosidosis is an inherited lysosomal storage disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. The condition may be classified into three major types based on the general age that signs and symptoms first appear: classic infantile (type 1); juvenile (type 2); and adult onset or chronic (type 3). Although the types differ in severity, their features may overlap significantly. GM1 gangliosidosis is caused by mutations in the GLB1 gene and is inherited in an autosomal recessive manner. Treatment is currently symptomatic and supportive.[1][2]

Symptoms

There are three general types of GM1 gangliosidosis, which differ in severity but can have considerable overlap of signs and symptoms.[1]

  • Classic infantile (type 1) GM1 gangliosidosis is the most severe type, with onset shortly after birth (usually within 6 months of age).[1] Affected infants typically appear normal until onset, but developmental regression (loss of acquired milestones) eventually occurs.[1] Signs and symptoms may include neurodegeneration, seizures, liver and spleen enlargement, coarsening of facial features, skeletal irregularities, joint stiffness, a distended abdomen, muscle weakness, an exaggerated startle response to sound, and problems with gait (manner of walking). About half of people with this type develop cherry-red spots in the eye. Children may become deaf and blind by one year of age.[3][4][5] Affected children typically do not live past 2 years of age.[1]
  • Juvenile (type 2) GM1 gangliosidosis is considered an intermediate form of the condition and may begin between the ages of 1 and 5. Features include ataxia, seizures, dementia, and difficulties with speech. This type progresses more slowly than type 1, but still causes decreased life expectancy (around mid-childhood or early adulthood).[1]
  • Adult (type 3) GM1 gangliosidosis may cause signs and symptoms to develop anywhere between the ages of 3 and 30. Affected people may have muscle atrophy, corneal clouding and dystonia.[3][4][5] Non-cancerous skin blemishes may develop on the lower part of the trunk of the body.[3] Adult GM1 is usually less severe and progresses more slowly than other forms of the condition.[3][4][5]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal diaphysis morphology
Abnormal shape of shaft of long bone
Abnormality of shaft of long bone of the limbs

[ more ]

0000940
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Aplasia/Hypoplasia of the abdominal wall musculature
Absent/small abdominal wall muscles
Absent/underdeveloped abdominal wall muscles

[ more ]

0010318
Arthralgia
Joint pain
0002829
Brain imaging abnormality
0410263
Coarse facial features
Coarse facial appearance
0000280
Coarse metaphyseal trabecularization
0100670
Decreased beta-galactosidase activity
0008166
Depressed nasal ridge
Flat nose
Recessed nasal ridge

[ more ]

0000457
Encephalitis
Brain inflammation
0002383
Ganglioside accumulation
0004345
Hyperreflexia
Increased reflexes
0001347
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Splenomegaly
Increased spleen size
0001744
Weight loss
0001824
30%-79% of people have these symptoms
Abnormality of extrapyramidal motor function
0002071
Abnormality of the cerebral white matter
0002500
Ataxia
0001251
Camptodactyly of finger
Permanent flexion of the finger
0100490
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Generalized dystonia
0007325
Generalized hirsutism
Excessive hairiness over body
0002230
Gingival overgrowth
Gum enlargement
0000212
Global developmental delay
0001263
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Hyperlordosis
Prominent swayback
0003307
Inguinal hernia
0000023
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue

[ more ]

0000158
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw

[ more ]

0000303
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment

[ more ]

0002167
Short stature
Decreased body height
Small stature

[ more ]

0004322
Skeletal dysplasia
0002652
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Thickened skin
Thick skin
0001072
Tremor
0001337
Unsteady gait
Unsteady walk
0002317
5%-29% of people have these symptoms
Abnormality of the scrotum
0000045
Bilateral tonic-clonic seizure with generalized onset
0025190
Blindness
0000618
Broad nasal tip
Broad tip of nose
Broad, upturned nose
Increased breadth of nasal tip
Increased breadth of tip of nose
Increased width of nasal tip
Increased width of tip of nose
Nasal tip, broad
Nasal tip, wide
Wide tip of nose

[ more ]

0000455
Cardiomyopathy
Disease of the heart muscle
0001638
Cherry red spot of the macula
0010729
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure

[ more ]

0001635
Corneal opacity
0007957
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Dysostosis multiplex
0000943
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Frontal bossing

Diagnosis

A diagnosis of GM1 gangliosidosis (GM1), can be made by either enzyme analysis of the beta-galactosidase enzyme, or by molecular genetic testing of the GLB1 gene. Despite the availability of molecular genetic testing, the mainstay of diagnosis will likely continue to be enzyme activity because of cost and difficulty in interpreting unclear results.[6] However, enzyme activity may not be predictive of carrier status in relatives of affected people. Carrier testing for at-risk family members is done with molecular genetic testing, and is possible if the disease-causing mutations in the family are already known.[6]

The Genetic Testing Registry (GTR) provides information about the labs that offer genetic testing for this condition. The intended audience for the GTR is health care providers and researchers. Therefore, patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

There is currently no effective medical treatment for GM1 gangliosidosis.[3][4] Symptomatic treatment for some of the neurologic signs and symptoms is available, but does not significantly alter the progression of the condition.[4][7] For example, anticonvulsants may initially control seizures. Supportive treatments may include proper nutrition and hydration, and keeping the affected individual's airway open.[3]

Bone marrow transplantation was reportedly successful in an individual with infantile/juvenile GM1 gangliosidosis; however, no long-term benefit was reported. Presymptomatic cord-blood hematopoietic stem-cell transplantation has been advocated by some as a possible treatment due to its success in other lysosomal storage disorders.[4] Active research in the areas of enzyme replacement and gene therapy for the condition is ongoing but has not yet advanced to human trials.[4][7]

Neurologic and orthopedic sequelae may prevent adequate physical activity, but affected individuals may benefit from physical and occupational therapy.[4]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss GM1 gangliosidosis. Click on the link to view a sample search on this topic.

          References

          1. GM1 gangliosidosis. Genetics Home Reference. August 2013; https://ghr.nlm.nih.gov/condition/gm1-gangliosidosis.
          2. Anna Caciotto, Maria Alice Donati, and Amelia Morrone. GM1 Gangliosidosis. Orphanet. May, 2012; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=354.
          3. NINDS Gangliosidoses Information Page. National Institute of Neurological Disorders and Stroke (NINDS). October 2011; https://www.ninds.nih.gov/Disorders/All-Disorders/Generalized-Gangliosidoses-Information-Page.
          4. Tegay D. GM1 Gangliosidosis. Medscape. March 29, 2012; https://emedicine.medscape.com/article/951637-overview.
          5. About Gangliosidosis-1 (GM-1). National Tay-Sachs and Allied Diseases Association, Inc.. October 3, 2012; https://www.ntsad.org/index.php/the-diseases/gm-1.
          6. Debra S Regier and Cynthia J Tifft. GLB1-Related Disorders. GeneReviews. October 17, 2013; https://www.ncbi.nlm.nih.gov/books/NBK164500/.
          7. GM1 Gangliosidosis Infantile. Hide & Seek Foundation for Lysosomal Disease Research. https://www.hideandseek.org/Diseases.html.

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