Schindler disease type 1

Alternate names

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

Definition

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.

Epidemiology

Schindler disease is very rare. Only a few individuals with each type of the disorder have been identified.

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.

Gene mutations

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.

Inheritance

Autosomal recessive inheritance, a 25% chance

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.

Signs and symptoms

Schindler disease type I, also called the infantile type, is the most severe form. Babies with Schindler disease type I appear healthy at birth, but by the age of 8 to 15 months they stop developing new skills and begin losing skills they had already acquired (developmental regression). As the disorder progresses, affected individuals develop blindness and seizures, and eventually they lose awareness of their surroundings and become unresponsive. People with this form of the disorder usually do not survive past early childhood.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal pyramidal sign
• Abnormality of brainstem morphology(Abnormal shape of brainstem)
• Cerebral visual impairment
• Developmental regression(Loss of developmental milestones)
• Generalized amyotrophy(Diffuse skeletal muscle wasting)
• Global developmental delay
• Hearing impairment(Deafness)
• Intellectual disability, severe(Early and severe mental retardation)
• Muscle weakness(Muscular weakness)
• Muscular hypotonia(Low or weak muscle tone)
• Seizure
• Spasticity(Involuntary muscle stiffness, contraction, or spasm)

30%-79% of people have these symptoms

• Abnormality of extrapyramidal motor function
• Autism
• Hemiplegia/hemiparesis(Paralysis or weakness of one side of body)
• Hyperkeratosis
• Myoclonus
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Optic atrophy
• Strabismus(Cross-eyed)
• Telangiectasia of the skin
• Vertigo(Dizzy spell)

5%-29% of people have these symptoms

• Aplasia/Hypoplasia of the cerebellum(Absent/small cerebellum)
• Hepatomegaly(Enlarged liver)
• Hypertrophic cardiomyopathy
• Enlarged and thickened heart muscle
• Lymphedema(Swelling caused by excess lymph fluid under skin)
• Paresthesia(Pins and needles feeling)

Diagnosis

• Amniocentesis or chorionic villus sampling can be used to screen for the disease before birth. After birth, urine tests, along with blood tests and skin biopsies can be used to diagnose Schindler disease.
• Genetic testing is also always an option, since different forms of Schindler disease have been mapped to the same gene on chromosome 22; though different changes (mutations) of this gene are responsible for the infantile- and adult-onset forms of the disease.

Treatment

Infants with Schindler disease tend to die within 4 years of birth, therefore, treatment for this form of the disease is mostly palliative.

NIH genetic and rare disease info

• NIH info on Schindler disease type 1

Schindler disease type 1 is a rare disease.

Schindler disease type 1 Resources
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