Objective: To describe the temporal emergence of PKAN symptoms and functional impairments across the spectrum of PKAN severity.

Background: PKAN, an autosomal recessive, progressive neurodegenerative disorder, is a heterogeneous disease. It may include dystonia, spasticity, rigidity, bradykinesia, postural instability, loss of ambulation and ability to communicate, feeding difficulties, psychiatric issues, and cognitive and visual impairment. Knowledge about the patient experience from symptom onset through diagnosis and further emergence of functional impairments is limited.

Method: Thirty-nine patients (aged ≥6 years with genetically confirmed PKAN) or their primary caregivers were interviewed using the PKAN-Activities of Daily Living (ADL) scale. The current study used PKAN-ADL total score quartiles to group patients by severity of impairment (Lowest [L] n=9, Second Lowest [SL] n=10, Third Lowest [TL] n=10, Highest [H] n=10). Age at onset of PKAN symptoms was examined across the severity of impairment groups.

Results: Across PKAN severity of impairment groups, disease duration did not significantly differ (P>0.05). Age at first symptom (median age H=1.0, TL=7.0, SL=10.0, L=14.0 years) and at PKAN diagnosis (median age H=7.0, TL=13.0, SL=10.0, L=15.0 years) did differ (P-values<0.05). Current speech, school, and eating/choking problems were present in ≥55% of patients across the spectrum of PKAN severity and there was a linear increase in the age at onset of these problems, with the youngest median age for H (6, 5, and 10 years, respectively) and the oldest median age for L (17, 14, and 16 years, respectively). A similar increase in age at onset (ie, H=youngest to SL/L=oldest) occurred for full time caregiving, unable to walk without help, and lost ability to walk at all, with an increase in the percentage of patients experiencing these problems from the lower to higher severity of impairment groups. Vision problems, lost ability to speak, feeding tube, and dystonic storm had varied temporal patterns across the PKAN spectrum.

Conclusion: These data suggest a temporal progression of symptoms and functional impairments across the spectrum of PKAN severity, with age at onset increasing as PKAN severity of impairment decreases. Therapies that prevent this symptom progression are urgently needed.

References: Marshall RD et al. A scale to assess activities of daily living in pantothenate kinase-associated neurodegeneration. Mov Disord Clin Pract. 2019;6:139-149.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/temporal-emergence-of-symptoms-and-functional-impairments-in-patients-with-pantothenate-kinase-associated-neurodegeneration-pkan/