Summary about Disease
Deficiency of acetyl-CoA:alpha-glucosaminide N-acetyltransferase (also known as Mucopolysaccharidosis IIIC or Sanfilippo syndrome type C) is a rare, inherited metabolic disorder characterized by the body's inability to properly break down specific complex sugar molecules called mucopolysaccharides (also known as glycosaminoglycans, or GAGs). This breakdown process requires the enzyme acetyl-CoA:alpha-glucosaminide N-acetyltransferase. A deficiency in this enzyme leads to the accumulation of heparan sulfate (a type of GAG) within cells, particularly in the brain and other organs, leading to progressive neurological deterioration.
Symptoms
Symptoms of Sanfilippo syndrome type C are similar to other types of Sanfilippo syndrome. These symptoms typically appear between ages 2 and 6. Common symptoms include:
Developmental delay or regression
Hyperactivity and behavioral problems
Intellectual disability
Sleep disturbances
Speech problems
Coarse facial features
Recurrent upper respiratory infections
Diarrhea
Seizures
Hearing loss
Causes
Sanfilippo syndrome type C is caused by mutations in the HGSNAT gene. This gene provides instructions for making the acetyl-CoA:alpha-glucosaminide N-acetyltransferase enzyme. Mutations in the *HGSNAT* gene lead to a deficiency or complete absence of the functional enzyme, resulting in the buildup of heparan sulfate within cells. This is inherited in an autosomal recessive pattern, meaning an affected individual must inherit two copies of the mutated gene (one from each parent) to develop the disorder.
Medicine Used
Currently, there is no cure for Sanfilippo syndrome type C, and treatment is primarily supportive. Management strategies focus on alleviating symptoms and improving the patient's quality of life.
Symptom management: Medications may be used to manage hyperactivity, sleep disturbances, seizures, and other behavioral or neurological symptoms.
Physical and occupational therapy: These therapies can help maintain motor skills and independence.
Speech therapy: Speech therapy can aid with communication difficulties.
Enzyme replacement therapy (ERT): ERT is not currently approved for Sanfilippo Type C.
Hematopoietic stem cell transplantation (HSCT): HSCT may be considered.
Gene therapy: Gene therapy clinical trials are currently underway.
Is Communicable
No, Sanfilippo syndrome type C is not communicable. It is a genetic disorder caused by inherited gene mutations and cannot be spread from person to person.
Precautions
There are no specific precautions to prevent Sanfilippo syndrome type C, as it is a genetic condition. Genetic counseling is recommended for families with a history of the disorder who are considering having children. This counseling can help them understand the risk of passing on the mutated gene and explore available options, such as genetic testing.
How long does an outbreak last?
Sanfilippo Syndrome Type C is not an infectious disease and does not have outbreaks. It is a genetic disorder that is present from birth and progresses over time.
How is it diagnosed?
Diagnosis of Sanfilippo syndrome type C involves:
Clinical Evaluation: A thorough medical history and physical examination to assess symptoms and developmental milestones.
Urine Tests: Elevated levels of heparan sulfate in the urine can suggest the possibility of Sanfilippo syndrome.
Enzyme Assay: Measuring the activity of acetyl-CoA:alpha-glucosaminide N-acetyltransferase in cultured skin fibroblasts or white blood cells. Low or absent enzyme activity confirms the diagnosis.
Genetic Testing: Identifying mutations in the HGSNAT gene through DNA sequencing.
Brain Imaging: MRI scans may show characteristic brain abnormalities.
Timeline of Symptoms
While there's variability, a general symptom timeline is as follows:
Early Childhood (around 2-6 years): Initial symptoms such as developmental delays, hyperactivity, and behavioral problems often become noticeable.
Preschool and Early School Years: Speech problems, sleep disturbances, and coarse facial features may become more apparent. Cognitive decline progresses.
Later Childhood and Adolescence: Intellectual disability becomes more severe, and motor skills decline. Seizures and other neurological complications may arise.
Adulthood: The disease progresses to a vegetative state. Life expectancy is significantly reduced.
Important Considerations
Early diagnosis is crucial: Although there's no cure, early diagnosis allows for timely supportive care and symptom management.
Genetic counseling is essential: Families should receive genetic counseling to understand the inheritance pattern and assess the risk of recurrence.
Research is ongoing: Research into potential therapies, including enzyme replacement therapy and gene therapy, offers hope for future treatments.
Support groups can be invaluable: Connecting with other families affected by Sanfilippo syndrome can provide emotional support and practical advice.
Palliative care: As the disease progresses, palliative care focuses on providing comfort and improving the quality of life for both the patient and their family.