Summary about Disease
Alpha-N-acetylglucosaminidase deficiency, also known as Sanfilippo syndrome type B (MPS IIIB), is a rare, inherited lysosomal storage disorder. It is caused by a deficiency of the enzyme alpha-N-acetylglucosaminidase, which is needed to break down a complex sugar molecule called heparan sulfate. The buildup of heparan sulfate leads to progressive damage to cells, tissues, and organs, particularly the brain. This results in a range of symptoms, primarily affecting the central nervous system. The severity of symptoms varies significantly between individuals.
Symptoms
Symptoms typically manifest in early childhood (between 2 and 6 years of age). Common symptoms include:
Developmental delay or regression (loss of previously acquired skills)
Intellectual disability
Behavioral problems (hyperactivity, aggression, sleep disturbances)
Speech problems
Mild skeletal abnormalities
Recurrent respiratory infections
Coarse facial features
Enlarged liver and spleen (hepatosplenomegaly)
Hearing loss
Causes
Sanfilippo syndrome type B is caused by mutations in the NAGLU gene. This gene provides instructions for making the alpha-N-acetylglucosaminidase enzyme. Mutations in the NAGLU gene disrupt the production of this enzyme, leading to its deficiency or malfunction. The deficiency of this enzyme prevents the proper breakdown of heparan sulfate, causing it to accumulate within lysosomes (cellular compartments responsible for waste processing) and causing cellular damage. The condition is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
Currently, there is no cure for Sanfilippo syndrome type B. Treatment is focused on managing symptoms and providing supportive care. This may include:
Physical therapy to maintain mobility and prevent contractures.
Speech therapy to improve communication skills.
Occupational therapy to help with daily living activities.
Medications to manage behavioral problems, seizures, or sleep disturbances.
Enzyme replacement therapy (ERT): Roctavian has shown success. (However, as of this writing, it is more advanced in approvals for MPS IIIA/Sanfilippo A, not IIIB)
Hematopoietic stem cell transplantation (HSCT): While sometimes considered, the effectiveness is variable and carries significant risks.
Gene therapy trials are under investigation.
Is Communicable
No, Sanfilippo syndrome type B (MPS IIIB) is not communicable. It is a genetic disorder caused by mutations in the NAGLU gene and is inherited from parents. It cannot be spread from person to person.
Precautions
Since Sanfilippo syndrome type B is a genetic condition, there are no precautions to prevent its occurrence in an affected individual after conception. For families with a history of the disorder, genetic counseling and carrier testing are recommended before planning a pregnancy. Once a child is diagnosed, precautions focus on managing their symptoms and preventing complications. This involves:
Following the care plan developed by medical professionals
Protecting the child from injuries, especially head injuries
Preventing and treating infections promptly
Ensuring appropriate nutrition and hydration
Creating a safe and supportive environment.
How long does an outbreak last?
Sanfilippo syndrome type B is not an infectious disease, and therefore, the concept of an "outbreak" does not apply. It is a chronic, progressive condition that lasts throughout the lifespan of the affected individual. The symptoms worsen over time.
How is it diagnosed?
Diagnosis of Sanfilippo syndrome type B typically involves:
Clinical evaluation: Review of the patient's symptoms and medical history.
Urine test: Measuring the levels of glycosaminoglycans (GAGs), specifically heparan sulfate, which are often elevated in MPS IIIB.
Enzyme assay: Measuring the activity of alpha-N-acetylglucosaminidase in blood leukocytes or cultured skin fibroblasts. A significantly reduced or absent enzyme activity confirms the diagnosis.
Genetic testing: Analyzing the NAGLU gene for mutations to confirm the diagnosis and provide genetic counseling.
Brain imaging (MRI): To assess the extent of brain damage.
Timeline of Symptoms
The timeline of symptoms can vary significantly, but a general progression is as follows:
Early Childhood (2-6 years): Subtle developmental delays, speech problems, and behavioral issues may become apparent.
Late Childhood (6-10 years): Cognitive decline becomes more noticeable, hyperactivity and behavioral problems worsen, and speech becomes more limited. Skeletal abnormalities and recurrent infections may also develop.
Adolescence: Severe intellectual disability, loss of motor skills, seizures, and progressive neurological deterioration. Individuals may become wheelchair-bound and require 24-hour care.
Adulthood: Life expectancy is typically shortened, with death occurring in the late teens or twenties, but some individuals may live longer with supportive care.
Important Considerations
Sanfilippo syndrome type B is a devastating disease with a significant impact on the affected individual and their family.
Early diagnosis and intervention are crucial to provide supportive care and improve quality of life.
Genetic counseling is essential for families with a history of the disorder.
Research is ongoing to develop new therapies, including enzyme replacement therapy and gene therapy.
Support groups and advocacy organizations can provide valuable resources and support for families affected by MPS IIIB.