Also known as Sanfilippo syndrome, this disorder develops as the result of an enzyme deficiency that normally breaks down the complex sugar molecules (mucopolysaccharides). As the result, it can accumulate in the cells of the central nervous system presenting neurological and developmental problems. There are four subtypes of this disorder; types A, B, C and D each presenting a specific genetic mutation. This condition is also a part of a large group of disorders known as lysosomal storage disorders that develop when molecules accumulate inside the lysosomes.
Causes
The mutations in the genes identified to cause this condition includes GNS, HGSNAT, NAGLU and SGSH which are essential for the production of enzymes that is necessary for the breakdown of sugar molecules called glycosaminoglycans (GAGs). The enzymes produced are involved in the breakdown of a subset of GAGs known as heparan sulfate. The genetic mutation in the SGSH gene causes the MPS IIIA, a mutation in the gene NAGLU causes MPS IIIB, mutations in the HGSNAT results in MPS IIIC and GNA genetic mutation develops MPS IIID. The genetic mutation can affect any one of this enzyme’s normal breakdown of heparin sulfate which can accumulate in cells particularly inside the lysosomes that are responsible for the digestion and recycling of various molecules. This disease is inherited in an autosomal recessive pattern meaning both the copies of the genes in each cell are defective. The parents of the affected individual each carry a single copy of the defective gene and don’t necessarily exhibit the symptoms of this condition.
Symptoms
The infants with this disease appear to be normal at birth but can present developmental delay by the age of 2 – 5 years. The mental and motor developmental problems occur followed by behavioral disturbances and intellectual decline. One of the common features of this condition is the severe behavioral disturbance which is considered to be one of the more difficult aspects of this disorder. Additional symptoms include excess hair growth, sleeping problems, mildly enlarged liver and/or spleen, speech delay, diarrhea, hernias, respiratory and ear infections, hearing loss and vision impairment. Death can occur among these children before the age of 10 years until their third or fourth decades of life.
Diagnosis
The initial diagnosis is made by measuring the mucopolysaccharides in the urine. This is followed by the enzyme activity in the blood or from the skin sample. The elevated levels of heparin sulfate in urine can help with diagnosing MPS III. The genetic testing can help confirm the genetic mutation responsible for developing this condition.
Treatment
There is no cure for this disease. The treatment for this condition is based on providing symptomatic and supportive care. These affected children often require the need for a multidisciplinary team to ensure the best treatment options and to devise an effective management plan. Enzyme replacement therapy has been approved as treatment options for these cases.
References
https://rarediseases.org/rare-diseases/mucopolysaccharidosis-type-iii/
https://rarediseases.info.nih.gov/diseases/7071/mucopolysaccharidosis-type-iiia
https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iii#inheritance
http://mpssociety.org/mps/mps-iii/
