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Pantothenate kinase-associated neurodegeneration
https://doi.org/10.30629/2658-7947-2025-30-4-44-50
Abstract
The article presents a description of a clinical case of atypical late form of pantothenate kinase-associated neurodegeneration (PKAN) in the terminal stage with debut in the fourth decade of life and rapidly progressive course. The most characteristic signs of the disease in this patient were parkinsonism syndrome, pyramidal symptoms, various hyperkinesis, decreased cognitive functions, depression. The diagnosis was based on the characteristic clinical picture and typical MRI signs in the form of the “tiger eye” symptom. Due to the lack of eff ective treatment methods at present, the patient received symptomatic treatment.
About the Authors
L. B. Novikova
Bashkir State Medical University
Russian Federation
Russian Federation
Ufa, Russia
A. P. Akopyan
Bashkir State Medical University
Russian Federation
Russian Federation
Ufa, Russia
K. M. Ziultsle
Bashkir State Medical University
Russian Federation
Russian Federation
Ufa, Russia
References
1. Kolarova H., Tan J., Strom T.M., Meitinger T., Wagner M., Klopstock T. Lifetime risk of autosomal recessive neurodegeneration with brain iron accumulation (NBIA) disorders calculated from genetic databases. EBioMedicine. 2022;77:103869. doi: 10.1016/j.ebiom.2022.103869
2. Di Meo I., Tiranti V. Classifi cation and molecular pathogenesis of NBIA syndromes. Eur J Paediatr Neurol. 2018;22(2):272–284. doi: 10.1016/j.ejpn.2018.01.008
3. Hayfl ick S.J., Kurian M.A., Hogarth P. Neurodegeneration with brain iron accumulation. HandbClin Neurol. 2018;147:293–305. doi: 10.1016/B978-0-444-63233-3.00019-1
4. Nassif D., Pereira J.S., Spitz M., Capitão C., Faria A. Neurodegeneration with brain iron accumulation: A case report. Dement Neuropsychol. 2016;10(2):160–164. doi: 10.1590/S1980-5764-2016DN1002014
5. Gregory Allison, Hayfl ick Susan J.Pantothenate Kinase-Associated Neurodegeneration. GeneReviews. Last Update: August 3, 2017. https://www.ncbi.nlm.nih.gov/books/NBK1490/
6. Huang Y., Wan Z., Tang Y., Xu J.,Laboret B., Nallamothu S., Yang Ch., Boxiang LiuB., Olivia Lu R., Lu B., Feng J., Cao J., Hayfl ick S., Wu Zh., ZhouB. Pantothenate kinase 2 interacts with PINK1 to regulate mitochondrial quality control via acetylCoA metabolism. Nat Commun. 2022;13(1):2412. doi: 10.1038/s41467-022-30178-x
7. Hayfl ickS.J., WestawayS.K., Levinson B., Zhou B., Johnson M.A., Ching K.H.L., Gitschier J. Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med. 2003;348(1):33–40. doi: 10.1056/NEJMoa020817
8. Voges L., Kupsch A. Renaming of Hallervorden-Spatz disease: the second man behind the name of the disease. J Neural Transm (Vienna). 2021;128(11):1635–1640. doi: 10.1007/s00702-021-02408-x
9. Munshi M.I., Yao S.J., Ben Mamoun C. Redesigning therapies for pantothenate kinase-associated neurodegeneration. J Biol Chem. 2022;298(3):101577. doi: 10.1016/j.jbc.2022.101577
10. Outlev K.M., Kruchinin E.V., Kozlov M.V., Mokin E.A., Akhmetianov M.A., Alekberov R.I., Lukashenok A.V., Autlev M.K., Yanieva Y.S. Hereditary neurodegenerations with iron accumulation in the brain (literature review). Ural Medical Journal. 2019;03(171):9–16. (In Russ.). doi: 10.25694/URMJ.2019.03.15
11. Shi X., Zheng F., Ye X., Li X, Zhao Q., Lin Z., Hu Y., Wang J. Basal ganglia calcifi cation and novel compound heterozygous mutations in the PANK2 gene in a Chinese boy with classic Pantothenate kinase-associated neurodegeneration: A case report. Medicine (Baltimore). 2018;97(15):e0316. doi: 10.1097/MD.0000000000010316
12. Shalash A.S., Rösler T.W., Abdelrahman I.Y., Abulmakarem H.S., Müller S.H., Hopfner F., Kuhlenbäumer G., Höglinger G.U., Salama M. Atypical pantothenate kinase-associated neurodegeneration with variable phenotypes in an Egyptian family. Heliyon. 2021;7(7):e07469. doi: 10.1016/j.heliyon.2021.e07469
13. Marshall R.D., Collins A., Escolar M.L., Jinnah H.A., Klopstock T., Kruer M.C., Videnovic A., Robichaux-Viehoever A., Burns C., Swett L.L., Revicki D.A., Bender R.H., Lenderking W.R. Diagnostic and clinical experience of patients with pantothenate kinase-associated neurodegeneration. Orphanet J Rare Dis. 2019;14(1):174. doi: 10.1186/s13023-019-1142-1
14. Brezavar D., Bonnen P.E. Incidence of PKAN determined by bioinformatic and population-based analysis of ~140,000 humans. Mol Genet Metab. 2019;128(4):463–469. doi: 10.1016/j.ymgme.2019.09.002
15. McNeill A., Birchall D., Hayfl ick S.J., Gregory A., Schenk J.F., Zimmerman E.A., Shang H., Miyajima H., Chinnery P.F. MRI distinguishes foir subtypes of neurodegeneration with brain iron accumulation. Neurology. 2008;18:1614–1619
16. Kopishinskaya S.V., Makushina S.V., Gustov A.V., Parshina E.V. Pantothenate kinase-associated neurodegeneration (Hallervorden-Spatz disease). Medical Almanac. 2013;1(25):150–152. (In Russ.).
17. Razmeh S., Habibi A.H., Orooji M., Alizadeh E., Moradiankokhdan K., Razmeh B. Pantothenate kinase-associated neurodegeneration: clinical aspects, diagnosis and treatments. Neurol Int. 2018;10(1):7516. doi: 10.4081/ni.2018.7516
18. Chang X., Zhang J., Jiang Y., Wang J., Wu Y. Natural history and genotype-phenotype correlation of pantothenate kinase-associated neurodegeneration. CNS NeurosciTher. 2020;26:754–761. doi: 10.1111/cns.13294
19. Choayb S., Adil H., Ali Mohamed D., Allali N., Chat L., El Haddad S. Eye of the Tiger Sign in Pantothenate Kinase-Associated Neurodegeneration. Case Rep Radiol. 2021;2021:6633217. doi: 10.1155/2021/6633217
20. Kruer M.C., Boddaert N., Schneider S.A., Houlden H.,Bhatia K.P., Gregory A., Anderson J.C., Rooney W.D., Hogarth P., Hayfl ick S.J. Neuroimaging features of neurodegeneration with brain iron accumulation. AJNR Am J Neuroradiol. 2012;33(3):407–414. doi: 10.3174/ajnr.A2677
21. Paprocka J., Machnikowska-Sokołowska M., Gruszczyńska K., Emich-Widera E. Neuroimaging of Basal Ganglia in Neurometabolic Diseases in Children. Brain Sci. 2020 Nov 12;10(11):849. doi: 10.3390/brainsci10110849
22. Perevoshchikova A.A., Yurkina N.V., Spichak I.I. Clinical case of Hallervorden-Spatzdisease. Pediatric Bulletin of the Southern Urals. 2022;2:92–100. (In Russ.).
23. Belinskaya V.V., Dutova T.I. Features of diagnostics of Hallervorden-Spatz disease (clinical observation). Universe of the brain. 2021;2:7–9. (In Russ.).
24. Gregory A., Polster B., Hayfl ick S. et al. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J. Med. Genet. 2009;2:73–80.
25. Hogarth P. Neurodegeneration with brain iron accumulation: diagnosis and management. J MovDisord. 2015;8(1):1–13. doi: 10.14802/jmd.14034
26. Hayfl ick S.J., Hartman M., Coryell J., Gitschier J., Rowley H. Brain MRI in neurodegeneration with brain iron accumulation with and without PANK2 mutations. AJNR Am J Neuroradiol. 2006;27:1230–33.
27. Reddy V., Saboo K., Reddy K., Kumar S., Acharya S. Pantothenate Kinase-Associated Neurodegeneration (PKAN) With Concomitant Blepharospasm: Unveiling a Clinical Enigma. Cureus. 2023;15(10):e46665. doi: 10.7759/cureus.46665
28. Sharma L.K., Subramanian C., Yun M.K., Frank M.W., White S.W., Rock C.O., Lee R.E., Jackowski S. A therapeutic approach to pantothenate kinase associated neurodegeneration. Nat Commun. 2018;9(1):4399. doi: 10.1038/s41467-018-06703-2
29. Pohane M.R., Dafre R., Sontakke N.G. Diagnosis and Treatment of Pantothenate Kinase-Associated Neurodegeneration (PKAN): A Systematic Review. Cureus. 2023;15(9):e46135. doi: 10.7759/cureus.46135
30. Klopstock T., Videnovic A., Bischoff A.T., Bonnet C., Cif L., Comella C., Сorrea-Vela M., Escolar M.L., Fraser J.L., Gonzalez V., Hermanowicz N., Jech R., Jinnah H.A., Kmiec T., Lang A., Martí M.J., Mercimek-Andrews S., Monduy M., Nimmo G.A.M., Perez-Dueñas B., Pfeiff er H.C.V., Planellas L., Roze E., Thakur N., Tochen L., Vanegas-Arroyave N., Zorzi G., Burns C., Greblikas F. Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase-Associated Neurodegeneration. Randomized Controlled Trial. Mov Disord. 2021;36(6):1342–1352. doi: 10.1002/mds.28392
31. Woo K.A., Kim H.J., Jeon S.H., Park H.R., Park K.W., Lee S.H., Chung S.J., Chae J.H., Paek S.H., Jeon B. Long-Term Outcomes of Deep Brain Stimulation in Pantothenate Kinase-Associated Neurodegeneration-Related Dystonia. J MovDisord. 2022 Sep;15(3):241–248. doi: 10.14802/jmd.22002
32. Garcia-Ruiz P.J., Ayerbe J., Vela Desojo L., Feliz C.E., Del Val Fernandez J. Deep brain stimulation for pantothenate kinase-associated neurodegeneration. Case Rep Neurol Med. 2015;2015:245735. doi: 10.1155/2015/245735
33. Baumeister F.A., Auer D.P., Hörtnagel K., Freisinger P., Meitinger T. The eye-of-the-tiger sign is not a reliable disease marker for Hallervorden-Spatz syndrome. Neuropediatrics. 2005;36:221–222.
34. Litvinenko I.V., Krasakov I.V., Trufanov A.G. Cerebral disorders of iron metabolism as the basis for the development and progression of neurodegenerative diseases. Bulletin of the Russian Military Medical Academy. 2018;20(3S):68–77. (In Russ.).
35. Ward R.J., Zucca F.A., Duyn J.H., Crichton R.R., Zecca L. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurology. 2014;13(10):1045–1060. doi: 10.1016/S1474-4422(14)70117-6
36. Hanna P.A., Benbadis S.R., Garg N., Fischer E. Pantothenate Kinase-Associated Neurodegeneration (PKAN) Updated: Oct 05, 2023. https://emedicine.medscape.com/article/1150519-overview?form=fpf
37. Руденская Г.Е., Захарова Е.Ю. Наследственные нейродегенерации с накоплением железа в мозге. Анналы клинической и экспериментальной неврологии. 2013;7(4):51–60. Rudenskaya G.E., Zakharova E.Yu. Hereditary Neurodegenerations with iron accumulation in the brain. Annals of Clinical and Experimental Neurology. 2013;7(4):51–60. (In Russ.).
38. Stoessl A.J. Neuroimaging in the early diagnosis of neurodegenerative disease. Translational Neurodegeneration. 2012;1:5. doi: 10.1186/2047-9158-1-5
39. Kurian M.A., Morgan N.V., MacPherson L., Foster K., Peake D., Gupta R., Philip S.G., Hendriksz C., Morton J.E.V., Kingston H.M., Rosser E.M., Wassmer E., Gissen P., Maher E.R. Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN)// Neurology. 2008;70(18):1623–1629. doi: 10.1212/01.wnl.0000310986.48286.8e
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For citations:
Novikova L.B., Akopyan A.P., Ziultsle K.M. Pantothenate kinase-associated neurodegeneration. Russian neurological journal. 2025;30(4):44-50. (In Russ.) https://doi.org/10.30629/2658-7947-2025-30-4-44-50
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