Details of Disease

General Information of Disease (ID: DIS50V55)

• Disease Name: Pantothenate kinase-associated neurodegeneration
• Synonyms: neuroaxonal dystrophy, late infantile; Pkan neuroaxonal dystrophy, juvenile-onset; brain iron accumulation type I syndrome; neurodegeneration with brain iron accumulation 1; Hallervorden-Spatz disease; neurodegeneration with brain iron accumulation type 1; NBIA1; pantothenate kinase-associated neurodegeneration; Hallervorden-Spatz syndrome; pigmentary pallidal degeneration; PKAN
• Definition: Pantothenate kinase-associated neurodegeneration (PKAN) is the most common type of neurodegeneration with brain iron accumulation (NBIA), a rare neurodegenerative disorder characterized by progressive extrapyramidal dysfunction (dystonia, rigidity, choreoathetosis), iron accumulation on the brain and axonal spheroids in the central nervous system.
• Disease Hierarchy:
  DISUSDSN: Neuroacanthocytosis
  DIS0G6PI: Disorder of phospholipids, sphingolipids and fatty acids biosynthesis
  DISRK4DZ: Neurodegeneration with brain iron accumulation
  DIS50V55: Pantothenate kinase-associated neurodegeneration
• Disease Identifiers:
  MONDO ID: MONDO_0009319
  MESH ID: D006211
  UMLS CUI: C0018523
  OMIM ID: 234200
  MedGen ID: 6708
  Orphanet ID: 157850
  SNOMED CT ID: 2992000

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
LRP2	TTPH1AJ	Strong	Biomarker	[1]
SNCA	TT08OSU	Strong	Biomarker	[2]

This Disease Is Related to 10 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
C19orf12	OTVSJ1AR	Limited	Biomarker	[3]
PLB1	OTZ6TTYV	Limited	Genetic Variation	[4]
PLA2G6	OT5FL0WU	moderate	Genetic Variation	[5]
ANKS4B	OT1MREUS	Strong	Biomarker	[6]
ECD	OT3L3PCU	Strong	Biomarker	[7]
MCF2L	OTEURA8N	Strong	Biomarker	[1]
PANK1	OT2CZVRT	Strong	Genetic Variation	[8]
PANK2	OTFBW889	Strong	Autosomal recessive	[9]
SMARCAL1	OTTKXLUZ	Strong	Biomarker	[6]
TECPR2	OT1UFECZ	Strong	Genetic Variation	[10]

References

• [1] Clinical course of patients with pantothenate kinase-associated neurodegeneration (PKAN) before and after DBS surgery.J Neurol. 2019 Dec;266(12):2962-2969. doi: 10.1007/s00415-019-09499-3. Epub 2019 Aug 29.
• [2] Extensive aggregation of -synuclein and tau in juvenile-onset neuroaxonal dystrophy: an autopsied individual with a novel mutation in the PLA2G6 gene-splicing site.Acta Neuropathol Commun. 2013 May 9;1:12. doi: 10.1186/2051-5960-1-12.
• [3] "Eye of tiger sign" mimic in an adolescent boy with mitochondrial membrane protein associated neurodegeneration (MPAN).Brain Dev. 2016 May;38(5):516-9. doi: 10.1016/j.braindev.2015.10.017. Epub 2015 Nov 18.
• [4] Neurodegeneration with brain iron accumulation.Handb Clin Neurol. 2011;100:161-72. doi: 10.1016/B978-0-444-52014-2.00009-4.
• [5] Pantothenate kinase-associated neurodegeneration is not a synucleinopathy.Neuropathol Appl Neurobiol. 2013 Feb;39(2):121-31. doi: 10.1111/j.1365-2990.2012.01269.x.
• [6] HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration. Neurology. 2002 Jun 11;58(11):1673-4. doi: 10.1212/wnl.58.11.1673.
• [7] Pantothenate kinase-associated neurodegeneration with increased lentiform nuclei cerebral blood flow.AJNR Am J Neuroradiol. 2006 Jan;27(1):212-3.
• [8] A therapeutic approach to pantothenate kinase associated neurodegeneration.Nat Commun. 2018 Oct 23;9(1):4399. doi: 10.1038/s41467-018-06703-2.
• [9] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [10] TECPR2 Associated Neuroaxonal Dystrophy in Spanish Water Dogs.PLoS One. 2015 Nov 10;10(11):e0141824. doi: 10.1371/journal.pone.0141824. eCollection 2015.