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      Patient and caregiver experiences with pantothenate kinase-associated neurodegeneration (PKAN): results from a patient community survey


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          Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive genetic disorder of PANK2, which enables mitochondrial synthesis of coenzyme A. Its loss causes neurodegeneration with iron accumulation primarily in motor-related brain areas. Symptoms include dystonia, parkinsonism, and other disabilities. PKAN has been categorized as classic PKAN, with an age of onset ≤ 10 years, rapid progression, and early disability or death; and atypical PKAN, with later onset, slower progression, generally milder, and more diverse symptom manifestations. Available treatments are mostly palliative. Information on the lived experience of patients with PKAN and their caregivers or on community-level disease burden is limited. It is necessary to engage patients as partners to expand our understanding and improve clinical outcomes. This patient-oriented research study used multiple-choice and free-form question surveys distributed by patient organizations to collect information on the manifestations and disease burden of PKAN. It also assessed respondents’ experiences and preferences with clinical research to inform future clinical trials.


          The analysis included 166 surveys. Most respondents (87%) were parents of a patient with PKAN and 7% were patients, with 80% from Europe and North America. The study cohort included 85 patients with classic PKAN (mean ± SD age of onset 4.4 ± 2.79 years), 65 with atypical PKAN (13.8 ± 4.79 years), and 16 identified as “not sure”. Respondents reported gait disturbances and dystonia most often in both groups, with 44% unable to walk. The classic PKAN group reported more speech, swallowing, and visual difficulties and more severe motor problems than the atypical PKAN group. Dystonia and speech/swallowing difficulties were reported as the most challenging symptoms. Most respondents reported using multiple medications, primarily anticonvulsants and antiparkinsonian drugs, and about half had participated in a clinical research study. Study participants reported the most difficulties with the physical exertion associated with imaging assessments and travel to assessment sites.


          The survey results support the dichotomy between classic and atypical PKAN that extends beyond the age of onset. Inclusion of patients as clinical research partners shows promise as a pathway to improving clinical trials and providing more efficacious PKAN therapies.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13023-023-02869-1.

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          Most cited references9

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          Grounded theory research: A design framework for novice researchers

          Background: Grounded theory is a well-known methodology employed in many research studies. Qualitative and quantitative data generation techniques can be used in a grounded theory study. Grounded theory sets out to discover or construct theory from data, systematically obtained and analysed using comparative analysis. While grounded theory is inherently flexible, it is a complex methodology. Thus, novice researchers strive to understand the discourse and the practical application of grounded theory concepts and processes. Objective: The aim of this article is to provide a contemporary research framework suitable to inform a grounded theory study. Result: This article provides an overview of grounded theory illustrated through a graphic representation of the processes and methods employed in conducting research using this methodology. The framework is presented as a diagrammatic representation of a research design and acts as a visual guide for the novice grounded theory researcher. Discussion: As grounded theory is not a linear process, the framework illustrates the interplay between the essential grounded theory methods and iterative and comparative actions involved. Each of the essential methods and processes that underpin grounded theory are defined in this article. Conclusion: Rather than an engagement in philosophical discussion or a debate of the different genres that can be used in grounded theory, this article illustrates how a framework for a research study design can be used to guide and inform the novice nurse researcher undertaking a study using grounded theory. Research findings and recommendations can contribute to policy or knowledge development, service provision and can reform thinking to initiate change in the substantive area of inquiry.
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            Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome.

            Hallervorden-Spatz syndrome is an autosomal recessive disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. Many patients with this disease have mutations in the gene encoding pantothenate kinase 2 (PANK2); these patients are said to have pantothenate kinase-associated neurodegeneration. In this study, we compared the clinical and radiographic features of patients with Hallervorden-Spatz syndrome with and without mutations in PANK2. One hundred twenty-three patients from 98 families with a diagnosis of Hallervorden-Spatz syndrome were classified on the basis of clinical assessment as having classic disease (characterized by early onset with rapid progression) or atypical disease (later onset with slow progression). Their genomic DNA was sequenced for PANK2 mutations. All patients with classic Hallervorden-Spatz syndrome and one third of those with atypical disease had PANK2 mutations. Whereas almost all mutations in patients with atypical disease led to amino acid changes, those in patients with classic disease more often resulted in predicted protein truncation. Patients with atypical disease who had PANK2 mutations were more likely to have prominent speech-related and psychiatric symptoms than patients with classic disease or mutation-negative patients with atypical disease. In all patients with pantothenate kinase-associated neurodegeneration, whether classic or atypical, T2-weighted magnetic resonance imaging (MRI) of the brain showed a specific pattern of hyperintensity within the hypointense medial globus pallidus. This pattern was not seen in any patients without mutations. PANK2 mutations are associated with all cases of classic Hallervorden-Spatz syndrome and one third of cases of atypical disease. A specific MRI pattern distinguishes patients with PANK2 mutations. Predicted levels of pantothenate kinase 2 protein correlate with the severity of disease. Copyright 2003 Massachusetts Medical Society
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              Natural history and genotype‐phenotype correlation of pantothenate kinase‐associated neurodegeneration

              Abstract Aims To investigate the natural history and genotype‐phenotype correlation of pantothenate kinase‐associated neurodegeneration. Methods We collected data of patients with PKAN by searching from available publications in English and Chinese. Patients diagnosed in our center (Peking University First Hospital) were also included. The difference in natural history and genotype between early‐onset (<10 year of age at onset) and late‐onset patients (≥10 year of age at onset) with PKAN was compared. Results A total of 248 patients were included. The median age at onset was 3.0 years in the early‐onset group and 18.0 years in the late‐onset group. Dystonia in lower limbs was the most common initial symptom in both groups. In the early‐onset group, the median interval between the disease onset and occurrence of oromandibular dystonia, generalized dystonia, loss of independent ambulance was 6.0 years, 5.0 years, and 5.0 years. The corresponding values in late‐onset group were 1.0 year, 4.0 years, and 6.0 years. About 20.0% died at median age of 12.5 years and 9.5 years after the onset in early‐onset group. About 2.0% of the late‐onset patients died during the follow‐up. A total of 176 mutations were identified. Patients carrying two null alleles in PANK2 showed significantly earlier age of disease onset and progressed more rapidly to loss of independent ambulance. Conclusions This study provided a comprehensive review on the natural history and genotype of 248 patients with PKAN. The results will serve as a historical control data for future clinical trial on PKAN.

                Author and article information

                Orphanet J Rare Dis
                Orphanet J Rare Dis
                Orphanet Journal of Rare Diseases
                BioMed Central (London )
                31 August 2023
                31 August 2023
                : 18
                : 257
                [1 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Department of Neurology, Friedrich-Baur-Institute, LMU Klinikum, , University Hospital of the Ludwig-Maximilians-Universität München, ; Munich, Germany
                [2 ]GRID grid.17089.37, ISNI 0000 0001 2190 316X, Department of Medical Genetics, Faculty of Medicine and Dentistry, , University of Alberta, ; Edmonton, Canada
                [3 ]CoA Therapeutics, 1800 Owens Street, Suite C-1200, San Francisco, CA 94158 USA
                [4 ]GRID grid.469792.7, ISNI 0000 0004 5905 7845, NBIA Disorders Association, ; El Cajon, USA
                [5 ]Association NBIA Poland, Warszawa, Poland
                [6 ]Hoffnungsbaum e.V., Würselen, Germany
                [7 ]ENACH Asociación, Seville, Spain
                [8 ]AISNAF, Rome, Italy
                [9 ]FUERAN, Santo Domingo, Dominican Republic
                [10 ]NBIA Suisse, Lausanne, Switzerland
                [11 ]GRID grid.411083.f, ISNI 0000 0001 0675 8654, Department of Paediatric Neurology, , Vall d`Hebron University Hospital, ; Barcelona, Spain
                [12 ]GRID grid.418955.4, ISNI 0000 0001 2237 2890, Institute of Psychiatry and Neurology, ; Warsaw, Poland
                [13 ]GRID grid.411484.c, ISNI 0000 0001 1033 7158, Department of Child Neurology, , Medical University of Lublin, ; Lublin, Poland
                [14 ]GRID grid.239553.b, ISNI 0000 0000 9753 0008, UPMC Children’s Hospital of Pittsburgh, ; Pittsburgh, CA USA
                Author information
                © Institut National de la Santé et de la Recherche Médicale (INSERM) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                : 11 January 2023
                : 23 August 2023
                Funded by: CoA Therapeutics
                Custom metadata
                © Institut National de la Santé et de la Recherche Médicale (INSERM) 2023

                Infectious disease & Microbiology
                hallervorden–spatz syndrome,nbia,neurodegeneration,iron accumulation,dystonia,pank2,atypical pkan,classic pkan,clinical outcomes assessment,patient-oriented


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