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Disease Profile

Schindler disease type 1

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.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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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)

Neuroaxonal dystrophy, Schindler type; Alpha-N-acetylgalactosaminidase deficiency, type 1; NAGA deficiency, type 1;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary

Schindler disease is an inherited condition that primarily causes neurological problems. There are three types of Schindler disease. Schindler disease type 1, also called the infantile type, is the most severe form. Babies with this condition appear healthy a birth, but by the age of 8 to 15 months they stop developing new skills and begin losing skills they had already acquired. As the condition progresses, affected individuals develop blindness and seizures, and eventually lose awareness of their surroundings and become unresponsive. People with this form of the condition usually don't survive past early childhood. Schindler disease type 1 is caused by mutations in the NAGA gene. The condition follows an autosomal recessive pattern of inheritance.[1]

Symptoms

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 pyramidal sign
0007256
Abnormality of brainstem morphology
Abnormal shape of brainstem
0002363
Cerebral visual impairment
0100704
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Generalized amyotrophy
Diffuse skeletal muscle wasting
Generalized muscle degeneration
Muscle atrophy, generalized

[ more ]

0003700
Global developmental delay
0001263
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation

[ more ]

0010864
Muscle weakness
Muscular weakness
0001324
Muscular hypotonia
Low or weak muscle tone
0001252
Seizure
0001250
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
30%-79% of people have these symptoms
Abnormality of extrapyramidal motor function
0002071
Autism
0000717
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Hyperkeratosis
0000962
Myoclonus
0001336
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Optic atrophy
0000648
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Telangiectasia of the skin
0100585
Vertigo
Dizzy spell
0002321
5%-29% of people have these symptoms
Aplasia/Hypoplasia of the cerebellum
Absent/small cerebellum
Absent/underdeveloped cerebellum

[ more ]

0007360
Hepatomegaly
Enlarged liver
0002240
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Lymphedema
Swelling caused by excess lymph fluid under skin
0001004
Paresthesia
Pins and needles feeling
Tingling

[ more ]

0003401
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Hyperreflexia
Increased reflexes
0001347
Increased urinary O-linked sialopeptides
0003461
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Osteopenia
0000938

Cause

Schindler disease type 1 is caused by mutations in the NAGA gene. This gene provides instructions for making the enzyme alpha-N-acetylgalactosaminidase.This enzyme works in the lysosomes (compartments within cells that digest and recycle materials) to help break down complexes called glycoproteins and glycolipids (sugar molecules attached to certain proteins and fats). More specifically, alpha-N-acetylgalactosaminidase helps remove a molecule called alpha-N-acetylgalactosamine from sugars in these complexes.[1]

Mutations in the NAGA gene interfere with the ability of the alpha-N-acetylgalactosaminidase enzyme to perform its role in breaking down glycoproteins and glycoliipids. These substances accumulate in the lysosomes and cause cells to malfunction and eventually die. Cell damage in the nervous system and other tissues and organs of the body leads to the signs and symptoms of Schindler disease type 1.[1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

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.

    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

        • 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 Schindler disease type 1. Click on the link to view a sample search on this topic.

          References

          1. Schindler disease. Genetics Home Reference (GHR). February 2010; https://ghr.nlm.nih.gov/condition/schindler-disease. Accessed 5/13/2015.

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