Schindler Disease Type I
Description
Schindler Disease Type I, also known as Schindler‘s disease, is a rare, inherited metabolic disorder characterized by a deficiency in the enzyme N-acetylglucosamine-6-sulfatase (GNS). This enzyme plays a critical role in the breakdown of mucopolysaccharides, complex sugar molecules found throughout the body, particularly in connective tissues. When GNS is deficient, these mucopolysaccharides accumulate in various organs, leading to a range of health problems.
Genes Involved
Schindler Disease Type I is caused by mutations in the GNS gene located on chromosome 17. This gene provides instructions for producing the GNS enzyme. When mutations occur, the enzyme is either absent or dysfunctional, leading to the accumulation of mucopolysaccharides.
Recognizing the Signs and Symptoms
The symptoms of Schindler Disease Type I typically appear in early childhood and can vary in severity. Common signs include:
- Liver enlargement (hepatomegaly): The liver may become enlarged and firm, often causing discomfort or pain.
- Splenomegaly: The spleen may also become enlarged.
- Developmental delays: Children with Schindler Disease Type I often experience delays in reaching developmental milestones, such as sitting, crawling, and walking.
- Skeletal abnormalities: Bone deformities and joint stiffness can occur, affecting mobility and gait.
- Cardiovascular problems: Heart valve defects and other cardiovascular issues may arise.
- Corneal clouding: Opacity of the cornea, the clear outer layer of the eye, can affect vision.
- Hearing impairment: Some individuals may experience hearing loss.
- Neurological problems: Seizures, intellectual disability, and behavioral issues are also possible.
- Facial dysmorphism: Distinctive facial features, such as a prominent forehead, flat nasal bridge, and thick lips, may be present.
Causes
Schindler Disease Type I is inherited in an autosomal recessive pattern. This means that both parents must carry a copy of the mutated gene for their child to inherit the disorder. If both parents are carriers, there is a 25% chance that their child will inherit the disease, a 50% chance that their child will be a carrier, and a 25% chance that their child will not inherit the gene at all.
Inheritance/recurrence risk
Since Schindler Disease Type I is inherited in an autosomal recessive pattern, the recurrence risk for subsequent children is 25% if both parents are carriers. Genetic testing can be helpful in determining carrier status and estimating the risk of having a child with the disorder.
