Diagnostic and clinical experience of patients with pantothenate kinase-associated neurodegeneration

• Type of Material: Article
• Authors: Randall D. Marshall, Retrophin Inc; Abigail Collins, University of Colorado; Maria L. Escolar, University of Pittsburgh; Hyder Jinnah, Emory University; Thomas Klopstock, University of Munich; Michael C. Kruer, University of Arizona; Aleksandar Videnovic, Harvard Medical School; Amy Robichaux-Viehoever, Washington University; Colleen Burns, Retrophin Inc; Laura L. Swett, Evidera Inc; Dennis A. Revicki, Evidera Inc; Randall H. Bender, Evidera Inc; William R. Lenderking, Evidera Inc
• Language: English
• Date: 2019-07-12
• Publisher: BMC (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © 2019 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13023-019-1142-1
• Title of Journal or Parent Work: Orphanet Journal of Rare Diseases
• ISSN: 1750-1172
• Volume: 14
• Issue: 1
• Start Page: 174
• End Page: 174
• Grant/Funding Information: Employees of the study sponsor were involved in the design of the study; in the collection, analysis, and interpretation of data; and in writing the manuscript.; Evidera received funding from Retrophin, Inc. to participate in the study and for the development of the first draft of this manuscript.; Editorial and writing support was provided by Lynanne McGuire, PhD, CMPP of MedVal Scientific Information Services, LLC (Princeton, NJ) and was funded by Retrophin, Inc.; Retrophin, Inc. provided the funding for the study.
• Keywords: Life Sciences & Biomedicine; Genetics & Heredity; Medicine, Research & Experimental; Burden of illness; Research & Experimental Medicine; PKAN; PKAN-ADL scale; Healthcare utilization; Science & Technology; SCALE; Caregiver
• Research Categories: Biology, Genetics; Biology, Neuroscience

Abstract

Background: Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegenerative disorder with brain iron accumulation (NBIA). Objectives: To assess PKAN diagnostic pathway, history, and burden across the spectrum of PKAN severity from patient and/or caregiver perspectives. Methods: Caregivers of patients (n = 37) and patients themselves (n = 2) were interviewed in a validation study of the PKAN-Activities of Daily Living (ADL) scale. The current study used quartiles of the PKAN-ADL total score to divide patients by severity of impairment (Lowest, Second Lowest, Third Lowest, Highest). Diagnostic and treatment history, healthcare utilization, disease burden, and caregiver experience were compared between groups. Results: The analyses included data from 39 patients. Mean age at PKAN symptom onset (P = 0.0007), initial MRI (P = 0.0150), and genetic testing (P = 0.0016) generally decreased across the PKAN severity spectrum. The mean duration of illness did not differ among PKAN severity groups (range, 9.7-15.2 years; P = 0.3029). First MRI led to diagnosis in 56.4% of patients (range, 30.0-90.0%). A mean (SD) of 13.0 (13.1) medical and 55.2 (78.5) therapy visits (eg, physical, speech) occurred in the past year. More patients in the higher PKAN severity groups experienced multiple current functional losses and/or earlier onset of problems (P-values < 0.0500). Over half (56.8%) of caregivers experienced a change in employment because of caregiving. The percentage of patients requiring full-time caregiving increased across the PKAN severity spectrum (range, 11.1-100%; P = 0.0021). Conclusions: PKAN diagnosis was often delayed, most probably due to low awareness. Considerable burden of functional impairment and high healthcare utilization were found across the PKAN severity spectrum.