KEGG DISEASE: Neurodegeneration with brain iron accumulation

DISEASE: Neurodegeneration with brain iron accumulation

Entry

H00833                      Disease

Name

Neurodegeneration with brain iron accumulation

Subgroup

Pantothenate kinase-associated neurodegeneration [DS:H02208]
Neuroferritinopathy [DS:H01779]
Aceruloplasminemia [DS:H02206]
Kufor-Rakeb syndrome [DS:H02207]

Description

Neurodegeneration with brain iron accumulation (NBIA) is a group of progressive extrapyramidal and cognitive disorders characterized by iron accumulation predominantly in the globus pallidus, as well as extensive axonal spheroids in various regions of the brain. The most frequent genetic form is the pantothenate kinase-2 associated neurodegeneration (PKAN) with a mutation in the pantothenate kinase 2 (PANK2) gene. Other forms are associated with a mutation in phospholipase A2 (PLA2G6), and FTL (neuroferritinopathy). A significant proportion of children with an NBIA phenotype have no genetic diagnosis and there are additional as yet undiscovered genes that account for a number of these cases.

Category

Nervous system disease

Brite

Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
  Metabolic disorders
   Disorders of metabolite absorption or transport
    5C64  Disorders of mineral absorption or transport
     H00833  Neurodegeneration with brain iron accumulation
Pathway-based classification of diseases [BR:br08402]
Cellular process
  nt06532  Autophagy
   H00833  Neurodegeneration with brain iron accumulation
  nt06535  Efferocytosis
   H00833  Neurodegeneration with brain iron accumulation
  nt06525  Ferroptosis
   H00833  Neurodegeneration with brain iron accumulation

Pathway

hsa04140

Autophagy - animal

hsa00770

Pantothenate and CoA biosynthesis

hsa04978

Mineral absorption

hsa04216

Ferroptosis

Network

nt06525 Ferroptosis
nt06532 Autophagy
nt06535 Efferocytosis

Gene

(NBIA1) PANK2 [HSA:80025] [KO:K09680]
(NBIA2A, NBIA2B) PLA2G6 [HSA:8398] [KO:K16343]
(NBIA3) FTL [HSA:2512] [KO:K13625]
(NBIA4) C19orf12 [HSA:83636] [KO:K23168]
(NBIA5) WDR45 [HSA:11152] [KO:K22991]
(NBIA6) COASY [HSA:80347] [KO:K02318]
(NBIA7) REPS1 [HSA:85021] [KO:K20068]
(NBIA8) CRAT [HSA:1384] [KO:K00624]
(NBIA9) FTH1 [HSA:2495] [KO:K00522]

Other DBs

ICD-11:

5C64.10

MeSH:

D006211 D019150 C565699 C548080

OMIM:

234200 256600 610217 606159 614298 300894 615643 617916 617917 620669

Reference

PMID:21550835

Authors

Friedman A, Arosio P, Finazzi D, Koziorowski D, Galazka-Friedman J

Title

Ferritin as an important player in neurodegeneration.

Journal

Parkinsonism Relat Disord 17:423-30 (2011)
DOI:10.1016/j.parkreldis.2011.03.016

Reference

PMID:21480873

Authors

Kurian MA, McNeill A, Lin JP, Maher ER

Title

Childhood disorders of neurodegeneration with brain iron accumulation (NBIA).

Journal

Dev Med Child Neurol 53:394-404 (2011)
DOI:10.1111/j.1469-8749.2011.03955.x

Reference

PMID:20882425

Authors

Kamate M, Mali R, Tonne V, Bubanale S

Title

'Eye-of-the-tiger' sign and classic pantothenate kinase associated neurodegeneration.

Journal

Indian J Pediatr 78:121-2 (2011)
DOI:10.1007/s12098-010-0234-7

Reference

PMID:11479594 (NBIA1)

Authors

Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ

Title

A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.

Journal

Nat Genet 28:345-9 (2001)
DOI:10.1038/ng572

Reference

PMID:16783378 (NBIA2A/NBIA2B)

Authors

Morgan NV, Westaway SK, Morton JE, Gregory A, Gissen P, Sonek S, Cangul H, Coryell J, Canham N, Nardocci N, Zorzi G, Pasha S, Rodriguez D, Desguerre I, Mubaidin A, Bertini E, Trembath RC, Simonati A, Schanen C, Johnson CA, Levinson B, Woods CG, Wilmot B, Kramer P, Gitschier J, Maher ER, Hayflick SJ

Title

PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.

Journal

Nat Genet 38:752-4 (2006)
DOI:10.1038/ng1826

Reference

PMID:15099026 (NBIA3)

Authors

Vidal R, Ghetti B, Takao M, Brefel-Courbon C, Uro-Coste E, Glazier BS, Siani V, Benson MD, Calvas P, Miravalle L, Rascol O, Delisle MB

Title

Intracellular ferritin accumulation in neural and extraneural tissue characterizes a neurodegenerative disease associated with a mutation in the ferritin light polypeptide gene.

Journal

J Neuropathol Exp Neurol 63:363-80 (2004)
DOI:10.1093/jnen/63.4.363

Reference

PMID:23269600 (NBIA4)

Authors

Hogarth P, Gregory A, Kruer MC, Sanford L, Wagoner W, Natowicz MR, Egel RT, Subramony SH, Goldman JG, Berry-Kravis E, Foulds NC, Hammans SR, Desguerre I, Rodriguez D, Wilson C, Diedrich A, Green S, Tran H, Reese L, Woltjer RL, Hayflick SJ

Title

New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN.

Journal

Neurology 80:268-75 (2013)
DOI:10.1212/WNL.0b013e31827e07be

Reference

PMID:23176820 (NBIA5)

Authors

Haack TB, Hogarth P, Kruer MC, Gregory A, Wieland T, Schwarzmayr T, Graf E, Sanford L, Meyer E, Kara E, Cuno SM, Harik SI, Dandu VH, Nardocci N, Zorzi G, Dunaway T, Tarnopolsky M, Skinner S, Frucht S, Hanspal E, Schrander-Stumpel C, Heron D, Mignot C, Garavaglia B, Bhatia K, Hardy J, Strom TM, Boddaert N, Houlden HH, Kurian MA, Meitinger T, Prokisch H, Hayflick SJ

Title

Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA.

Journal

Am J Hum Genet 91:1144-9 (2012)
DOI:10.1016/j.ajhg.2012.10.019

Reference

PMID:24360804 (NBIA6)

Authors

Dusi S, Valletta L, Haack TB, Tsuchiya Y, Venco P, Pasqualato S, Goffrini P, Tigano M, Demchenko N, Wieland T, Schwarzmayr T, Strom TM, Invernizzi F, Garavaglia B, Gregory A, Sanford L, Hamada J, Bettencourt C, Houlden H, Chiapparini L, Zorzi G, Kurian MA, Nardocci N, Prokisch H, Hayflick S, Gout I, Tiranti V

Title

Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.

Journal

Am J Hum Genet 94:11-22 (2014)
DOI:10.1016/j.ajhg.2013.11.008

Reference

PMID:29395073 (NBIA7 NBIA8)

Authors

Drecourt A, Babdor J, Dussiot M, Petit F, Goudin N, Garfa-Traore M, Habarou F, Bole-Feysot C, Nitschke P, Ottolenghi C, Metodiev MD, Serre V, Desguerre I, Boddaert N, Hermine O, Munnich A, Rotig A

Title

Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation.

Journal

Am J Hum Genet 102:266-277 (2018)
DOI:10.1016/j.ajhg.2018.01.003

Reference

PMID:37660254 (NBIA9)

Authors

Shieh JT, Tintos-Hernandez JA, Murali CN, Penon-Portmann M, Flores-Mendez M, Santana A, Bulos JA, Du K, Dupuis L, Damseh N, Mendoza-Londono R, Berera C, Lee JC, Phillips JJ, Alves CAPF, Dmochowski IJ, Ortiz-Gonzalez XR

Title

Heterozygous Nonsense Variants in the Ferritin Heavy Chain Gene FTH1 Cause a Neuroferritinopathy.

Journal

HGG Adv 4:100236 (2023)
DOI:10.1016/j.xhgg.2023.100236

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