SNP Shot: Genomic Insights

Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a disorder that primarily impacts the central nervous system (brain and spinal cord). A key characteristic is neurodegeneration, a decline in neurological function, which leads to many of the condition's features. While other body systems can be affected, the physical signs are often subtle in the early stages.

Individuals with MPS III usually appear normal at birth. However, signs and symptoms typically emerge in early childhood. These early indicators can include frequent ear and throat infections or digestive issues, but often present as mild developmental delays or speech impediments. Behavioral problems tend to worsen, with children exhibiting restlessness, hyperactivity, destructiveness, anxiety, impulsivity, fearlessness, or aggression. Some children may display features of autism spectrum disorder, which involves difficulties with social interaction and communication. An increased tendency to chew on objects or engage in oral exploration (hyperorality) is also common, as are sleep disturbances. The condition leads to progressive intellectual disability and loss of previously learned skills (developmental regression or dementia). In the later stages of MPS III, seizures, mobility loss, and movement disorders may develop.

The physical features associated with MPS III are generally less pronounced compared to other forms of mucopolysaccharidosis. Individuals typically exhibit mildly "coarse" facial features, a prominent forehead, an enlarged head (macrocephaly), and thick hair and eyebrows. Some individuals may experience short stature, joint stiffness, or mild dysostosis multiplex, which refers to multiple skeletal abnormalities visible on X-rays.

Individuals with MPS III often have a slightly enlarged liver (mild hepatomegaly) or spleen (mild splenomegaly), as well as a soft bulge near the belly button (umbilical hernia) or in the lower abdomen (inguinal hernia). Cardiac issues may also arise, including weakening of the heart muscle (cardiomyopathy), irregular heart rhythms (arrhythmia), or heart valve problems. Chronic diarrhea and recurring upper respiratory and ear infections are common. Hearing loss and vision problems can also occur in individuals with MPS III.

MPS III is categorized into types IIIA, IIIB, IIIC, and IIID, based on their distinct genetic causes. While the different types share similar signs and symptoms, MPS IIIA tends to manifest earlier and progress more rapidly. Individuals with MPS III generally survive into adolescence or their early to mid-adult years.

Inheritance:

The condition follows an autosomal recessive inheritance pattern. This means that both copies of the responsible gene in each cell must have a mutation for the condition to develop. Parents of a child with an autosomal recessive condition each carry one copy of the mutated gene but usually don't exhibit any signs or symptoms of the condition themselves.