A Prospective Natural History Study of Mucopolysaccharidosis Type IIIA

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• 作者：Elsa G. Shapiro ; PhD¹ ; ^{shapi004@umn.edu" class="auth_mail" title="E-mail the corresponding author} ; Igor Nestrasil ; MD¹ ; Kathleen A. Delaney ; BA¹ ; Kyle Rudser ; PhD² ; Victor Kovac ; BA¹ ; Nitin Nair ; PhD³ ; ^&lowast ; ; Charles W. Richard III ; MD³ ; ^&dagger ; ; Patrick Haslett ; MD³ ; ^&Dagger ; ; Chester B. Whitley ; PhD ; MD¹
• 关键词：AEq ; Age-equivalent score ; BSID-III ; Bayley Scales of Infant and Toddler Development ; Third Edition ; CSF ; Cerebrospinal fluid ; DQ ; Developmental quotient ; FPSS ; Four-Point Scoring System ; GAG ; Glycosaminoglycan ; HS ; Heparan sulfate ; KABC-II ; Kaufman Assessment Battery for Children ; Second Edition ; MPS IH ; Mucopolysaccharidosis type IH ; MPS IIIA ; Mucopolysaccharidosis type IIIA ; MRI ; Magnetic resonance imaging ; p-tau ; phospho-tau ; RP ; Rapidly progressing ; SGSH ; N-sulphoglucosamine sulphohydrolase
• 刊名：The Journal of Pediatrics
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：170
• 期：Complete
• 页码：278-287.e4
• 全文大小：2405 K

文摘

To characterize the clinical course of mucopolysaccharidosis type IIIA (MPS IIIA), and identify potential endpoints for future treatment trials.

Study design

Children with a confirmed diagnosis of MPS IIIA, functioning above a developmental age of 1 year, were followed for up to 2 years. Cognitive status and brain atrophy were assessed by standardized tests and volumetric magnetic resonance imaging, respectively. Liver and spleen volumes and cerebrospinal fluid and urine biomarker levels were measured.

Results

Twenty-five children, from 1.1 to 18.4 years old, were enrolled, and 24 followed for at least 12 months. 19 exhibited a rapidly progressing (RP) form of MPS IIIA, and 5, a more slowly progressing form. Children with RP plateaued in development by 30 months, followed by rapid regression after 40-50 months. In patients with RP, cognitive developmental quotients showed consistent steep declines associated with progressive cortical gray matter atrophy. Children with slowly progressing had a similar but more prolonged course. Liver and spleen volumes were approximately double normal size, and cerebrospinal fluid and urine heparin sulfate levels were elevated and relatively constant over time.

Conclusion

Developmental quotient and cortical gray matter volume are sensitive markers of disease progression in MPS IIIA, and may have utility as clinical endpoints in treatment trials. For optimal outcomes, treatment may need to be instituted in children before the onset of steep cognitive decline and brain atrophy.

Trial registration

ClinicalTrials.gov: NCT01047306.