Longitudinal natural history of pediatric subjects affected with mucopolysaccharidosis IIIB

• Published in: The Journal of pediatrics 2022-10, Vol.249, p.50-58.e2
• Main Authors: Okur, Ilyas, Ezgu, Fatih, Giugliani, Roberto, Muschol, Nicole, Koehn, Anja, Amartino, Hernan, Harmatz, Paul, de Castro Lopez, Maria J., Couce, Maria Luz, Lin, Shuan-Pei, Batzios, Spyros, Cleary, Maureen, Solano, Martha, Peters, Heidi, Lee, Joy, Nestrasil, Igor, Shaywitz, Adam J., Maricich, Stephen M., Kuca, Bernice, Kovalchin, Joseph, Zanelli, Eric
• Format: Article
• Language: English
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2022.06.005

To characterize the longitudinal natural history of disease progression in pediatric subjects affected with mucopolysaccharidosis IIIB (MPS IIIB). Children with a confirmed diagnosis of MPS IIIB (n=65) were enrolled into one of two natural history studies and followed for up to 4 years. Cognitive and adaptive behavior functions were analyzed in all subjects and volumetric magnetic resonance imaging (MRI) analysis of liver, spleen and brain as well as levels of heparan sulfate (HS) and heparan sulfate non-reducing ends (HS-NRE) were measured in a subset of subjects. The majority of MPS IIIB subjects achieve an apex on both cognition and adaptive behavior age-equivalent scales between 3 and 6 years of age. Development quotients for both cognition and adaptive behavior follow a linear trajectory by which subjects reach a nadir with score < 25 for an age equivalent of 24 months by 8 years of age on average and by 13½ years at the latest. All tested subjects (n=22) had HS and HS-NRE levels in CSF and plasma above normal range and signs of hepatomegaly. Subjects lost 26 mL of brain volume (-2.7%) on average over 48 weeks, entirely due to a loss of cortical gray matter (32 mL or -6.5%). MPS IIIB subjects are parts of a single continuum based on cognitive decline and cortical gray matter atrophy. Although a few subjects have an attenuated phenotype, the majority of MPS IIIB patients follow predicted trajectories for both cognition and adaptive behavior.