Natural Progression of Neurological Disease in Mucopolysaccharidosis Type II

OBJECTIVE: Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder characterized by insufficiency of the iduronate-2-sulfatase enzyme, which results in excess heparan and dermatan sulfates within the lysosomes of various tissues and organs, including the central nervous system. The purpose of this study was to investigate the natural progression of neurologic disease in a large cohort of patients evaluated with standardized testing at a single institution. METHODS: During the period of December 2002 to October 2010, patients with MPS II were referred to the Program for Neurodevelopmental Function in Rare Disorders. A retrospective review of patient data was performed, which included the use of detailed questionnaires that addressed medical history, notes from previous health care providers, and the results of a multidisciplinary evaluation that lasted 4 to 6 hours and was performed by a team of neurodevelopmental pediatricians, speech pathologists, psychologists, audiologists, psychometricians, and occupational and physical therapists. Patients were evaluated annually for management of disease progression. RESULTS: A total of 50 male patients with MPS II were evaluated over 152 encounters. Two distinct subgroups of children were identified. One subset of patients had normal cognitive, speech and language, and adaptive functions whereas the other showed a dramatic decline in these areas. All patients developed fine and gross motor deficits. CONCLUSION: The natural progression of MPS II manifests as 2 divergent and distinct neurologic phenotypes with similar somatic disease. Patients may have primary neural parenchymal disease with cognitive involvement or may maintain normal cognitive abilities. Pediatrics 2011;127:e1258-e1265