Summary about Disease
Heparan N-sulfatase deficiency, also known as Sanfilippo syndrome type A (MPS IIIA), is a rare, inherited metabolic disorder that affects the body's ability to break down and recycle large sugar molecules called glycosaminoglycans (GAGs), specifically heparan sulfate. This deficiency leads to the accumulation of heparan sulfate in various tissues and organs, causing progressive damage, particularly in the brain and spinal cord. This results in severe neurological decline.
Symptoms
Symptoms typically appear between ages 2 and 6, though can be earlier. Common symptoms include:
Developmental delay or regression
Intellectual disability
Behavioral problems (hyperactivity, aggression, sleep disturbances)
Speech difficulties
Seizures
Coarse facial features
Hearing loss
Skeletal abnormalities (mild)
Diarrhea
Enlarged liver and spleen (hepatosplenomegaly)
Causes
Sanfilippo syndrome type A is caused by mutations in the SGSH gene. This gene provides instructions for making the heparan N-sulfatase enzyme. When the gene is mutated, the enzyme is deficient or absent, leading to the accumulation of heparan sulfate. It is inherited in an autosomal recessive pattern, meaning 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 A. Treatment focuses on managing symptoms and providing supportive care. Symptomatic treatment may include:
Medications to control seizures
Medications to manage behavioral problems
Physical therapy to maintain mobility
Speech therapy to improve communication
Enzyme replacement therapy (investigational, not widely available)
Hematopoietic stem cell transplantation (HSCT) - may slow progression in some cases, particularly when performed early in the disease course
Gene therapy (under investigation)
Is Communicable
No, Sanfilippo syndrome type A is not communicable. It is a genetic disorder, meaning it is caused by a gene mutation and cannot be spread from person to person.
Precautions
Since Sanfilippo syndrome is a genetic disorder, there are no precautions to prevent acquiring the disease itself. Genetic counseling and testing are important for families with a history of the disorder to understand the risk of having affected children. General supportive precautions are:
Ensuring a safe and supportive environment for the affected individual
Providing appropriate medical care to manage symptoms
Regular monitoring by specialists
Avoiding situations that may trigger behavioral problems
How long does an outbreak last?
Sanfilippo Syndrome is not an infectious disease and therefore does not have outbreaks. The disease is a chronic, progressive condition. Affected individuals experience a gradual decline in physical and cognitive abilities throughout their lives.
How is it diagnosed?
Diagnosis of Sanfilippo syndrome type A typically involves:
Clinical evaluation: Assessing symptoms and medical history.
Urine test: Measuring the level of heparan sulfate, which is usually elevated in affected individuals.
Enzyme assay: Measuring the activity of heparan N-sulfatase enzyme in blood or skin cells (fibroblasts). Significantly reduced or absent enzyme activity confirms the diagnosis.
Genetic testing: Analyzing the SGSH gene for mutations. This can confirm the diagnosis and also be used for carrier testing in family members.
Brain imaging (MRI): To assess the extent of brain damage.
Timeline of Symptoms
The timeline of symptoms can vary, but generally follows this pattern:
Infancy/Early Childhood (0-2 years): Often appear normal or show subtle developmental delays.
Early Childhood (2-6 years): Symptoms become more apparent, including speech delays, behavioral problems, and hyperactivity.
Childhood (6-10 years): Intellectual disability progresses, behavioral problems worsen, and seizures may develop. Motor skills decline.
Late Childhood/Adolescence: Progressive loss of cognitive and motor function, eventually leading to a vegetative state. Life expectancy is typically into the teens or early twenties, although some individuals may live longer with intensive support.
Important Considerations
Genetic Counseling: Crucial for families to understand the inheritance pattern and recurrence risk.
Early Diagnosis: While there is no cure, early diagnosis can allow for timely intervention and supportive care.
Supportive Care: Focuses on managing symptoms and improving quality of life.
Research and Clinical Trials: Ongoing research is aimed at developing new treatments, including enzyme replacement therapy, gene therapy, and substrate reduction therapy. Families should explore opportunities to participate in clinical trials.
Family Support: The progressive nature of the disease can be emotionally and physically challenging for families. Support groups and respite care can be helpful.