Mucopolysaccharidosis III, commonly referred to as Sanfilippo Syndrome, is a lysosomal storage disorder. It is part of a larger grouping of mucopolysaccharidosis diseases, but is distinguished by solely affecting the metabolism of heparan sulfates. Due to the decrease in production or lack of the enzymes necessary for the breakdown of the heparan sulfates, these glycosaminoglycans, or mucopolysaccharides, repeating chains of carbohydrates commonly found attached to proteoglycans, are unable to degrade. Thus, the lysosomal accumulation and urinary excretion lead to the onset and clinical onset of Sanfilippo Syndrome. Characterized by severe central nervous system (CNS) degradation, onset typically begins to manifest between the ages of 2 and 6 years. Patients are characterized with progressive mental deterioration leading to severe dementia. Behavioral problems are often present initially and are a tell-tale sign with hyperactive behaviors. Additional symptoms include epilepsy, frequent ear, nose, and throat infections, sleeping problems, and recurrent diarrhea.
At the Vannberg Lab, we are currently working on "Whole Genome Sequencing of a Mucopolysaccharidosis Patient". This project is a collaborative effort between Vannberg and Jordan lab at Georgia Tech and University of Libre in Cali Columbia. We have carried out complete genome sequencing of a Colombian individual to discern the genetic basis of suspected Sanfillippo syndrome in an Afro-Colombian family. The work involved finding and analyzing potentially deleterious regions of the genome that has an association with this disease. These regions are typically variants that include single nucleotide polymorphisms (SNP’s), structural variants (SV’s) and insertions/deletions (INDEL’s). We are studying these variants in a few genes of our interest. These genes code for proteins that are found to be involved in pathways found in diseased phenotype. Also, we are trying to identify the change in the structure and functions of the proteins due to these variants to better understand the disease.