Details of Disease

General Information of Disease (ID: DISRK4DZ)

• Disease Name: Neurodegeneration with brain iron accumulation
• Synonyms: NBIA; neurodegeneration with brain iron accumulation
• Definition: Neurodegeneration with brain iron accumulation (NBIA, formerly Hallervorden-Spatz syndrome) encompasses a group of rare neurodegenerative disorders characterized by progressive extrapyramidal dysfunction (dystonia, rigidity, choreoathetosis), iron accumulation in the brain and the presence of axonal spheroids, usually limited to the central nervous system.|Editor note: check relationship to PKAN
• Disease Hierarchy:
  DISO5FAY: Inborn error of metabolism
  DISHSV8Z: Neuroaxonal dystrophy
  DISFWL8F: Hereditary dementia
  DISPN7D2: Inherited neurodegenerative disorder
  DISWDM9J: Iron metabolism disease
  DISOJJ2D: Movement disorder
  DISRK4DZ: Neurodegeneration with brain iron accumulation
• Disease Identifiers:
  MONDO ID: MONDO_0018307
  MESH ID: C538421
  UMLS CUI: C2931845
  MedGen ID: 444156
  Orphanet ID: 385

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
C9orf72	TTA4SHR	moderate	Genetic Variation	[1]
COASY	TT4YO0Z	Strong	Biomarker	[2]
CRAT	TTC8M31	Strong	Genetic Variation	[3]
PLA2G1B	TT9V5JH	Strong	Biomarker	[4]
SGSH	TTPJ2SH	Strong	Biomarker	[5]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC52A3	DTBVQIO	Disputed	Biomarker	[1]

This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
FA2H	OT8HA13U	Limited	Genetic Variation	[6]
ATP13A2	OTKWBUGK	Strong	Genetic Variation	[7]
DCAF17	OTFNVJLN	Strong	Biomarker	[2]
DDHD1	OTWTHOWK	Strong	Biomarker	[8]
FBXO7	OTGTN8TJ	Strong	Genetic Variation	[9]
FTL	OTYQA8A6	Strong	Biomarker	[2]
PANK1	OT2CZVRT	Strong	Genetic Variation	[10]
PLA2G6	OT5FL0WU	Strong	Genetic Variation	[11]
PLB1	OTZ6TTYV	Strong	Biomarker	[4]
PRKRA	OTUTVZZU	Strong	Genetic Variation	[12]
PRPS1	OTN3A6CN	Strong	Biomarker	[13]
RAB39B	OTDCLLT0	Strong	Genetic Variation	[14]
REPS1	OTX4ERRK	Strong	Genetic Variation	[15]

References

• [1] Mutation screening of SLC52A3, C19orf12, and TARDBP in Iranian ALS patients.Neurobiol Aging. 2019 Mar;75:225.e9-225.e14. doi: 10.1016/j.neurobiolaging.2018.11.003. Epub 2018 Nov 16.
• [2] Review: Insights into molecular mechanisms of disease in neurodegeneration with brain iron accumulation: unifying theories.Neuropathol Appl Neurobiol. 2016 Apr;42(3):220-41. doi: 10.1111/nan.12242. Epub 2015 Jun 2.
• [3] CRAT missense variants cause abnormal carnitine acetyltransferase function in an early-onset case of Leigh syndrome.Hum Mutat. 2020 Jan;41(1):110-114. doi: 10.1002/humu.23901. Epub 2019 Sep 23.
• [4] A new PLA2G6 mutation in a family with infantile neuroaxonal dystrophy.J Neurol Sci. 2017 Oct 15;381:209-212. doi: 10.1016/j.jns.2017.08.3260. Epub 2017 Sep 1.
• [5] Transcranial ultrasound in neurodegeneration with brain iron accumulation (NBIA).Eur J Paediatr Neurol. 2012 Mar;16(2):175-8. doi: 10.1016/j.ejpn.2011.07.009. Epub 2011 Aug 3.
• [6] FAHN/SPG35: a narrow phenotypic spectrum across disease classifications.Brain. 2019 Jun 1;142(6):1561-1572. doi: 10.1093/brain/awz102.
• [7] Iron dysregulation in movement disorders.Neurobiol Dis. 2012 Apr;46(1):1-18. doi: 10.1016/j.nbd.2011.12.054. Epub 2012 Jan 12.
• [8] Mutations in DDHD1, encoding a phospholipase A1, is a novel cause of retinopathy and neurodegeneration with brain iron accumulation.Eur J Med Genet. 2017 Dec;60(12):639-642. doi: 10.1016/j.ejmg.2017.08.015. Epub 2017 Aug 14.
• [9] Neuroimaging studies and whole exome sequencing of PLA2G6-associated neurodegeneration in a family with intrafamilial phenotypic heterogeneity.Parkinsonism Relat Disord. 2015 Apr;21(4):402-6. doi: 10.1016/j.parkreldis.2015.01.010. Epub 2015 Jan 17.
• [10] Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations.Neurobiol Aging. 2012 Apr;33(4):814-23. doi: 10.1016/j.neurobiolaging.2010.05.009. Epub 2010 Jul 21.
• [11] Impaired iPLA(2) activity affects iron uptake and storage without iron accumulation: An in vitro study excluding decreased iPLA(2) activity as the cause of iron deposition in PLAN.Brain Res. 2019 Jun 1;1712:25-33. doi: 10.1016/j.brainres.2019.01.036. Epub 2019 Jan 29.
• [12] Rare causes of dystonia parkinsonism.Curr Neurol Neurosci Rep. 2010 Nov;10(6):431-9. doi: 10.1007/s11910-010-0136-0.
• [13] Genetic and phenotypic variability of optic neuropathies.Expert Rev Neurother. 2013 Apr;13(4):357-67. doi: 10.1586/ern.13.19.
• [14] High frequency of beta-propeller protein-associated neurodegeneration (BPAN) among patients with intellectual disability and young-onset parkinsonism.Neurobiol Aging. 2015 May;36(5):2004.e9-2004.e15. doi: 10.1016/j.neurobiolaging.2015.01.020. Epub 2015 Jan 30.
• [15] Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation. Am J Hum Genet. 2018 Feb 1;102(2):266-277. doi: 10.1016/j.ajhg.2018.01.003.