Rare Ophthalmology News

Disease Profile

Galactosialidosis

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

All ages

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ICD-10

E77.1

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)

Goldberg syndrome; Neuraminidase deficiency with beta-galactosidase deficiency; Lysosomal protective protein deficiency of;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

Summary

Galactosialidosis affects many different body systems, including the brain, eyes, muscles, and skeleton. There are three different types: early infantile, late infantile and juvenile/adult. The most common type is juvenile/adult galactosialidosis. Individuals with this type start developing symptoms in adolescence. Symptoms include difficulty walking, vision problems, spine abnormalities, dark red spots on the skin, and intellectual disability that gets worse with time. Symptoms of the early infantile and late infantile types are more severe and begin in infancy or early childhood. In these types, the symptoms tend to get worse over time and are associated with decreased survival. All three types of galactosialidosis are caused by variations in the CTSA gene and are inherited in an autosomal recessive pattern. Galactosialidosis is diagnosed based on a clinical exam, the symptoms, and genetic testing. Treatment is focused on managing the symptoms.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with galactosialidosis. These features may be different from person to person, even between people with the same type. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Infants with early infantile galactosialidosis have symptoms that usually appear before or at the time of birth. The signs and symptoms of include:[1][2]

  • Abnormal fluid build up in the fetus or newborn (hydrops fetalis)
  • Enlarged liver and/or spleen (hepatosplenomegaly)
  • Enlarged heart (cardiomyopathy)
  • Abnormal bone development (dysostosis multiplex)
  • Cherry red spot on the back of the eye
  • Kidney disease that gets worse with time
  • Facial features that are described as 'coarse'

Symptoms of the late infantile type of galactosialidosis usually start after 6 months of age, and are similar, but less severe, to those of the early infantile type. Additional features include hearing and vision loss, growth problems, and seizures.[1][2] 

The juvenile/adult type of galactosialidosis has symptoms that are somewhat different than those of the other two types. Symptoms typically start in adolescence, but the age at onset and severity is variable. Symptoms include:[1][2] 

  • Difficulty coordinating movements (ataxia)
  • Muscle twitches (myoclonus)
  • Seizures
  • Visual loss
  • Dark red spots on the skin (angiokeratomas)

The symptoms of the early and late infantile types of galactosialidosis often lead to a shortened life span. The symptoms of the juvenile/adult type vary in severity and age of onset. The symptoms include intellectual disability that gets worse with time, but lifespan is not generally affected.

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 vertebral morphology
0003468
Cherry red spot of the macula
0010729
Coarse facial features
Coarse facial appearance
0000280
Corneal opacity
0007957
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Intellectual disability
Mental deficiency
Mental-retardation
Mental retardation, nonspecific
Mental retardation

[ more ]

0001249
Seizure
0001250
Skeletal dysplasia
0002652
5%-29% of people have these symptoms
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Conjunctival telangiectasia
Small dilated blood vessels near membrane covering front of eye and eyelids
0000524
Decreased beta-galactosidase activity
0008166
Dysostosis multiplex
0000943
Hemangioma
Strawberry mark
0001028
Nonimmune hydrops fetalis
0001790
Opacification of the corneal stroma
0007759
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe

[ more ]

0003510
Visceromegaly
0003271

Cause

Galactosialidosis occurs when the CTSA gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[4]

Diagnosis

Galactosialidosis is diagnosed based on the symptoms, a clinical exam, and the results of genetic testing for variants in the CTSA gene.[2] The type of galactosialidosis is determined by the age that symptoms begin.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment for galactosialidosis is focused on managing the symptoms.[1] 

    Specialists involved in the care of someone with galactosialidosis may include:

    • Medical geneticist
    • Neurologist
    • Ophthalmologist

    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

      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.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • 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 Galactosialidosis. Click on the link to view a sample search on this topic.

          References

          1. Annunziata I, d'Azzo A. Galactosialidosis: historic aspects and overview of investigated and emerging treatment options. Expert Opin Orphan Drugs. 2017; 5(2):131-141. https://pubmed.ncbi.nlm.nih.gov/28603679.
          2. Sade Sláma T, GarbF, Kölker S, Hoffmann GF, Ries M. Quantitative natural history characterization in a cohort of 142 published cases of patients with galactosialidosis-A cross-sectional study.. J Inherit Metab Dis. 2019; 42(2):295-302. https://pubmed.ncbi.nlm.nih.gov/30693535.
          3. Prada CE, Gonzaga-Jauregui C, Tannenbaum R, et al. Clinical utility of whole-exome sequencing in rare diseases: Galactosialidosis. Eur J Med Genet. 2014; 57(7):339-344. https://pubmed.ncbi.nlm.nih.gov/24769197.
          4. Galactosialidosis; GSL. Online Mendelian Inheritance in Man. Updated 7/15/2016; https://www.omim.org/entry/256540.

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