The Neurobehavioral Phenotype in Mucopolysaccharidosis Type IIIB: an Exploratory Study

Area of Science:

• Neuroscience
• Genetics
• Pediatrics

Background:

• Mucopolysaccharidosis Type III (MPS III) encompasses subtypes A and B, characterized by severe neurobehavioral phenotypes.
• Behavioral abnormalities in MPS III significantly impact patient quality of life and present parenting challenges.
• Previous studies identified autistic symptoms and Klüver-Bucy-type syndrome in MPS IIIA.

Purpose of the Study:

• To delineate the neurobehavioral phenotype in patients with MPS IIIB.
• To compare the behavioral characteristics of MPS IIIB with MPS IIIA and Hurler syndrome (MPS IH).
• To investigate potential differences in the onset and progression of behavioral symptoms between MPS IIIB and MPS IIIA.

Main Methods:

• A cohort of 10 MPS IIIB patients (age >6) was compared to 9 MPS IIIA patients and 8 younger MPS IH patients.
• Neurobehavioral assessments included the Autism Diagnostic Observation Schedule (ADOS), Sanfilippo Behavior Rating Scale (SBRS), and the Risk Room procedure.
• Disease severity and cognitive ability were evaluated, alongside amygdala brain volumes from MRI scans.

Main Results:

• MPS IIIB patients displayed similar autistic features to MPS IIIA on the ADOS.
• Unlike MPS IIIA, MPS IIIB patients showed reduced fear responses in the Risk Room, similar to MPS IH.
• MPS IIIB patients exhibited more inattention and fearfulness, with potentially earlier onset of some symptoms compared to MPS IIIA.

Conclusions:

• MPS IIIB patients over age six share significant neurobehavioral similarities with MPS IIIA, including autistic features and a Klüver-Bucy-like syndrome.
• Lack of fear, poor attention, and autistic-like symptoms are key characteristics of MPS IIIB.
• Further research is needed to document the early development of these behaviors in young MPS IIIB patients to inform clinical trials and patient management.