Mucopolysaccharidosis type 3

Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a group of rare inherited lysosomal storage disorders caused by deficiency of one of four enzymes involved in the degradation of heparan sulfate, a type of glycosaminoglycan (GAG). There are four subtypes: MPS IIIA (caused by mutations in the SGSH gene encoding heparan N-sulfatase), MPS IIIB (NAGLU gene encoding N-acetyl-alpha-glucosaminidase), MPS IIIC (HGSNAT gene encoding heparan-alpha-glucosaminide N-acetyltransferase), and MPS IIID (GNS gene encoding N-acetylglucosamine-6-sulfatase). The accumulation of undegraded heparan sulfate primarily affects the central nervous system, making MPS III the most neurologically severe of the mucopolysaccharidoses. The disease typically presents in early childhood, usually between ages 2 and 6, with progressive neurological deterioration as the hallmark feature. Early symptoms include speech delay, behavioral disturbances (hyperactivity, aggression, sleep disturbances), and progressive intellectual disability. Unlike other MPS types, somatic features such as coarse facial features, skeletal abnormalities, and organomegaly tend to be relatively mild. Children may experience recurrent ear infections, diarrhea, and mild hepatomegaly. As the disease progresses, affected individuals develop severe dementia, loss of motor skills, seizures, and eventually become wheelchair-bound and unable to communicate. Most patients do not survive beyond the second or third decade of life. Currently, there is no approved curative treatment for MPS III. Management is primarily supportive and symptomatic, including behavioral management, seizure control, sleep management with melatonin, and multidisciplinary care involving neurologists, speech therapists, and physiotherapists. Several therapeutic approaches are under active investigation, including enzyme replacement therapy, gene therapy, substrate reduction therapy, and hematopoietic stem cell transplantation, though none have yet demonstrated definitive clinical benefit in large-scale trials. Early diagnosis through clinical suspicion, urinary GAG analysis, enzyme activity assays, and genetic testing is important for family counseling and potential enrollment in clinical trials.

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