Mucopolysaccharidosis Type III (MPS III Sanfilippo syndrome)

Description

Mucopolysaccharidosis Type III (MPS III), also known as Sanfilippo syndrome, is a rare genetic disorder that affects the body‘s ability to break down complex sugars called glycosaminoglycans (GAGs). This buildup of GAGs in cells, particularly in the brain, leads to a range of symptoms affecting physical development, cognitive abilities, and behavior.

Genes Involved

Genes Involved:

MPS III is caused by mutations in one of four genes:

SGSH (sulfamidase): Responsible for the breakdown of heparan sulfate (HS) in MPS IIIA.
NAGLU (N-acetylglucosaminidase): Involved in the breakdown of HS in MPS IIIB.
HGSNAT (heparan-alpha-glucosaminidase): Plays a role in the breakdown of HS in MPS IIIC.
GNS (glucosamine-6-sulfatase): Necessary for the breakdown of HS and chondroitin sulfate (CS) in MPS IIID.

Recognizing the Signs and Symptoms

Recognizing the Signs and Symptoms:

Developmental Delays: Children with MPS III may experience delays in reaching developmental milestones like walking, talking, and problem-solving.
Behavioral Issues: These can include hyperactivity, aggression, and self-injurious behaviors.
Cognitive Decline: As the disease progresses, individuals may experience intellectual decline and loss of cognitive function.
Physical Features: Some individuals may exhibit characteristic physical features such as a coarse facial appearance, short stature, and joint stiffness.
Hearing Loss: Hearing impairment is a common complication of MPS III.
Sleep Disturbances: Sleep difficulties and problems with sleep patterns are frequently reported.
Respiratory Issues: Respiratory problems, including recurrent infections and difficulty breathing, can arise.
Cardiac Complications: Heart problems, such as enlarged heart or valve abnormalities, may develop.
Vision Problems: Vision issues, including corneal clouding or optic nerve atrophy, can occur.
Gastrointestinal Problems: Stomach and bowel issues, such as constipation and reflux, may present.

Causes

Causes:

MPS III is an inherited condition caused by a mutation in one of the four genes mentioned above. This means that both parents must carry the gene for the child to be affected. If both parents are carriers, there is a 25% chance that their child will inherit the disorder, a 50% chance their child will be a carrier, and a 25% chance their child will not inherit the disorder.

Inheritance/recurrence risk

Inheritance or Recurrence Risk:

MPS III is an autosomal recessive disorder. This means that both parents must carry a copy of the mutated gene for their child to inherit the condition. If both parents are carriers, there‘s a 25% chance of having a child with MPS III, a 50% chance of having a carrier child, and a 25% chance of having a child without the gene mutation.

WES Whole Exome Sequencing