What are the other Names for this Condition? (Also known as/Synonyms)

• Alpha-N-Acetylgalactosaminidase Deficiency, Type 1
• NAGA Deficiency, Type 1
• Neuroaxonal Dystrophy, Schindler type

What is Schindler Disease Type 1? (Definition/Background Information)

• 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

(Source: Schindler Disease Type 1; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Schindler Disease Type 1? (Age and Sex Distribution)

• Schindler Disease Type 1 is a rare, congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Schindler Disease Type 1? (Predisposing Factors)

• A positive family history may be an important risk factor, since Schindler Disease Type 1 is an inherited condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Schindler Disease Type 1? (Etiology)

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
• Mutations in the NAGA gene interfere with the ability of the alpha-N-acetylgalactosaminidase enzyme to perform its role in breaking down glycoproteins and glycolipids
• 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
• Schindler Disease Type 1 is inherited in an autosomal recessive pattern. This means that both copies of the gene in each cell have mutations
• The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically so not show signs and symptoms of the condition

(Source: Schindler Disease Type 1; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Schindler Disease Type 1?

The signs and symptoms of Schindler Disease Type 1 include:

• Hyperreflexia
• Increased urinary O-linked sialic peptides
• Osteopenia

Very frequently present symptoms in 80-99% of the cases:

• Abnormal pyramidal signs
• Abnormality of brain stem morphology
• Cortical visual impairment
• Developmental regression
• Generalized amyotrophy
• Hearing impairment
• Intellectual disability, severe
• Muscular hypotonia
• Seizures
• Spasticity

Frequently present symptoms in 30-79% of the cases:

• Abnormality of extrapyramidal motor function
• Autism
• Hemiplegia/hemiparesis
• Hyperkeratosis
• Myoclonus
• Nystagmus
• Optic atrophy
• Strabismus
• Telangiectasia of the skin
• Vertigo

Occasionally present symptoms in 5-29% of the cases:

• Hepatomegaly
• Hypertrophic cardiomyopathy
• Lymphedema
• Parethesia

(Source: Schindler Disease Type 1; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Schindler Disease Type 1 Diagnosed?

Schindler Disease Type 1 is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the Possible Complications of Schindler Disease Type 1?

The complications of Schindler Disease Type 1 may include:

• Severe intellectual problems
• Vision defects
• Heart abnormalities

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Schindler Disease Type 1 Treated?

There is no cure for Schindler Disease Type 1, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Schindler Disease Type 1 be Prevented?

Currently, Schindler Disease Type 1 may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Schindler Disease Type 1? (Outcomes/Resolutions)

• The prognosis of Schindler Disease Type 1 is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Schindler Disease Type 1:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/rare-disorders/