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

Randall D. Marshall,
Abigail Collins,
Maria L. Escolar,
H. A. Jinnah,
Thomas Klopstock,
Michael C. Kruer,
Aleksandar Videnovic,
Amy Robichaux-Viehoever,
Colleen BurnsEmail author,
Laura L. Swett,
Dennis A. Revicki,
Randall H. Bender and
William R. Lenderking

Orphanet Journal of Rare Diseases201914:174

https://doi.org/10.1186/s13023-019-1142-1

Received: 1 March 2019
Accepted: 25 June 2019
Published: 12 July 2019

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.