Pantothenate Kinase-associated Neurodegeneration (PKAN) and PLA2G6-associated Neurodegeneration (PLAN): Review of Two Major Neurodegeneration with Brain Iron Accumulation (NBIA) Phenotypes

Overview

Journal Int Rev Neurobiol

Specialties Biology
Neurology
Psychiatry

Date 2013 Nov 12

PMID 24209433

Citations 43

Authors

Manju A Kurian

Susan J Hayflick

Affiliations

Soon will be listed here.

Abstract

Neurodegeneration with brain iron accumulation (NBIA) comprises a heterogeneous group of disorders characterized by the presence of radiologically discernible high brain iron, particularly within the basal ganglia. A number of childhood NBIA syndromes are described, of which two of the major subtypes are pantothenate kinase-associated neurodegeneration (PKAN) and PLA2G6-associated neurodegeneration (PLAN). PKAN and PLAN are autosomal recessive NBIA disorders due to mutations in PANK2 and PLA2G6, respectively. Presentation is usually in childhood, with features of neurological regression and motor dysfunction. In both PKAN and PLAN, a number of classical and atypical phenotypes are reported. In this chapter, we describe the clinical, radiological, and genetic features of these two disorders and also discuss the pathophysiological mechanisms postulated to play a role in disease pathogenesis.

Citing Articles

Understanding genetic variants in context.

Sinnott-Armstrong N, Fields S, Roth F, Starita L, Trapnell C, Villen J Elife. 2024; 13.

PMID: 39625477 PMC: 11614383. DOI: 10.7554/eLife.88231.

Case report: Asymmetric bilateral deep brain stimulation for the treatment of pantothenate kinase-associated neurodegeneration in a patient: a unique case of atypical PKAN with a novel heterozygous PANK2 mutation.

Hong G, Zhang Z, Wang P, Li G, Zhang W, Zou H Front Hum Neurosci. 2024; 18:1448606.

PMID: 39479227 PMC: 11521929. DOI: 10.3389/fnhum.2024.1448606.

Functional impairments in NBIA patients: Preliminary results.

Syczewska M, Steplowska A, Szczerbik E, Kalinowska M, Cwyl M Intractable Rare Dis Res. 2024; 13(3):172-177.

PMID: 39220277 PMC: 11350201. DOI: 10.5582/irdr.2024.01019.

Role of Botulinum Toxin in Treatment of Secondary Dystonia: A Case Series and Overview of Literature.

Mohanty D, Riordan H, Hedera P Toxins (Basel). 2024; 16(7.

PMID: 39057926 PMC: 11281616. DOI: 10.3390/toxins16070286.

Localized Pantothenic Acid (Vitamin B5) Reductions Present Throughout the Dementia with Lewy Bodies Brain.

Scholefield M, Church S, Xu J, Patassini S, Cooper G J Parkinsons Dis. 2024; 14(5):965-976.

PMID: 38820022 PMC: 11307062. DOI: 10.3233/JPD-240075.

References

Krause M, Fogel W, Tronnier V, Pohle S, Hortnagel K, Thyen U . Long-term benefit to pallidal deep brain stimulation in a case of dystonia secondary to pantothenate kinase-associated neurodegeneration. Mov Disord. 2006; 21(12):2255-7. DOI: 10.1002/mds.21166. View

Guimaraes J, Santos J . Generalized freezing in Hallervorden-Spatz syndrome: case report. Eur J Neurol. 1999; 6(4):509-13. DOI: 10.1046/j.1468-1331.1999.640509.x. View

Paisan-Ruiz C, Bhatia K, Li A, Hernandez D, Davis M, Wood N . Characterization of PLA2G6 as a locus for dystonia-parkinsonism. Ann Neurol. 2008; 65(1):19-23. PMC: 9016626. DOI: 10.1002/ana.21415. View

Nardocci N, Zorzi G, Farina L, Binelli S, Scaioli W, Ciano C . Infantile neuroaxonal dystrophy: clinical spectrum and diagnostic criteria. Neurology. 1999; 52(7):1472-8. DOI: 10.1212/wnl.52.7.1472. View

Kuo Y, Duncan J, Westaway S, Yang H, Nune G, Xu E . Deficiency of pantothenate kinase 2 (Pank2) in mice leads to retinal degeneration and azoospermia. Hum Mol Genet. 2004; 14(1):49-57. PMC: 2117329. DOI: 10.1093/hmg/ddi005. View

Strecker K, Hesse S, Wegner F, Sabri O, Schwarz J, Schneider J . Eye of the tiger sign in multiple system atrophy. Eur J Neurol. 2007; 14(11):e1-2. DOI: 10.1111/j.1468-1331.2007.01925.x. View

Shevell M . Hallervorden and history. N Engl J Med. 2003; 348(1):3-4. DOI: 10.1056/NEJMp020158. View

Mubaidin A, Roberts E, Hampshire D, Dehyyat M, Shurbaji A, Mubaidien M . Karak syndrome: a novel degenerative disorder of the basal ganglia and cerebellum. J Med Genet. 2003; 40(7):543-6. PMC: 1735513. DOI: 10.1136/jmg.40.7.543. View

McNeill A, Birchall D, Hayflick S, Gregory A, Schenk J, Zimmerman E . T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation. Neurology. 2008; 70(18):1614-9. PMC: 2706154. DOI: 10.1212/01.wnl.0000310985.40011.d6. View

10.

Molinuevo J, Marti M, Blesa R, Tolosa E . Pure akinesia: an unusual phenotype of Hallervorden-Spatz syndrome. Mov Disord. 2003; 18(11):1351-3. DOI: 10.1002/mds.10520. View

11.

Zorzi G, Zibordi F, Chiapparini L, Bertini E, Russo L, Piga A . Iron-related MRI images in patients with pantothenate kinase-associated neurodegeneration (PKAN) treated with deferiprone: results of a phase II pilot trial. Mov Disord. 2011; 26(9):1756-9. DOI: 10.1002/mds.23751. View

12.

Wada H, Kojo S, Seino K . Mouse models of human INAD by Pla2g6 deficiency. Histol Histopathol. 2013; 28(8):965-9. DOI: 10.14670/HH-28.965. View

13.

Benke T, Butterworth B . Palilalia and repetitive speech: two case studies. Brain Lang. 2001; 78(1):62-81. DOI: 10.1006/brln.2000.2445. View

14.

Freeman K, Gregory A, Turner A, Blasco P, Hogarth P, Hayflick S . Intellectual and adaptive behaviour functioning in pantothenate kinase-associated neurodegeneration. J Intellect Disabil Res. 2007; 51(Pt. 6):417-26. PMC: 2099459. DOI: 10.1111/j.1365-2788.2006.00889.x. View

15.

Dooling E, Schoene W, Richardson Jr E . Hallervorden-Spatz syndrome. Arch Neurol. 1974; 30(1):70-83. DOI: 10.1001/archneur.1974.00490310072012. View

16.

Baburina I, Jackowski S . Cellular responses to excess phospholipid. J Biol Chem. 1999; 274(14):9400-8. DOI: 10.1074/jbc.274.14.9400. View

17.

Houlden H, Lincoln S, Farrer M, Cleland P, Hardy J, Orrell R . Compound heterozygous PANK2 mutations confirm HARP and Hallervorden-Spatz syndromes are allelic. Neurology. 2003; 61(10):1423-6. DOI: 10.1212/01.wnl.0000094120.09977.92. View

18.

Balsinde J, Balboa M . Cellular regulation and proposed biological functions of group VIA calcium-independent phospholipase A2 in activated cells. Cell Signal. 2005; 17(9):1052-62. DOI: 10.1016/j.cellsig.2005.03.002. View

19.

Hartig M, Hortnagel K, Garavaglia B, Zorzi G, Kmiec T, Klopstock T . Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation. Ann Neurol. 2006; 59(2):248-56. DOI: 10.1002/ana.20771. View

20.

Shields D, Sharma N, Gale J, Eskandar E . Pallidal stimulation for dystonia in pantothenate kinase-associated neurodegeneration. Pediatr Neurol. 2007; 37(6):442-5. DOI: 10.1016/j.pediatrneurol.2007.08.006. View