Long‐term cognitive follow‐up in children treated for Maroteaux‐Lamy syndrome. Issue 2 (8th October 2015) - Ebbink, Berendine J.
Abstract: Background: It remains unclear to what extent the brain is affected by Maroteaux‐Lamy syndrome (MPS VI), a progressive lysosomal storage disorder. While enzyme replacement therapy (ERT) elicits positive effects, the drug cannot cross the blood–brain barrier. We therefore studied cognitive development and brain abnormalities in the Dutch MPS VI patient population treated with ERT. Methods: In a series of 11 children with MPS VI (age 2 to 20 years), we assessed cognitive functioning and brain magnetic resonance imaging prospectively at the start of ERT and at regular times thereafter up to 4.8 years. We also assessed the children's clinical characteristics, their siblings' cognitive development, and their parents' educational levels. Results: The patients' intelligence scores ranged from normal to mentally delayed (range test scores 52–131). In 90 %, their scores remained fairly stable during follow‐up, generally lying in the same range as their siblings' test scores (median for patients = 104, median for siblings = 88) and comparing well with the parental educational levels. Native‐speaking patients had higher intelligence test scores than non‐native‐speaking patients. Two patients, both with high baseline glycosaminoglycan levels in their urine and severe mutations in the arylsulfatase B gene, scored clearly lower than expected. Patients with pY210C performed best. Brain abnormalities were aspecific, occurring more in patients with severe symptoms. Conclusion: Our study shows that cognitive development in MPS VI patients is determined not only by familial and social‐background factors, but, in patients with a severe form of the disease, also by the disease itself. Therefore in patients with severe disease presentation cognition should be monitored carefully.