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Neurodegeneration with brain iron accumulation 8(NBIA8)

MedGen UID:
1645224
Concept ID:
C4693587
Disease or Syndrome
Synonyms: NBIA8; NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 8
 
Gene (location): CRAT (9q34.11)
 
Monarch Initiative: MONDO:0054764
OMIM®: 617917

Definition

Neurodegeneration with brain iron accumulation-8 (NBIA8) is characterized by iron accumulation in the basal ganglia and manifests as a progressive extrapyramidal syndrome with dystonia, rigidity, and choreoathetosis (Drecourt et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of NBIA, see NBIA1 (234200). [from OMIM]

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Sensory neuropathy
MedGen UID:
101791
Concept ID:
C0151313
Disease or Syndrome
Peripheral neuropathy affecting the sensory nerves.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Iron accumulation in brain
MedGen UID:
866729
Concept ID:
C4021076
Finding
An abnormal build up of iron (Fe) in brain tissue.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Increased circulating lactate concentration
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).

Professional guidelines

PubMed

Patwal R, Pai NM, Ganjekar S, Udupi GA, M P, M S, Kesavan M, Desai G
Bipolar Disord 2022 Dec;24(8):840-843. Epub 2022 Oct 6 doi: 10.1111/bdi.13262. PMID: 36164835
Painous C, van Os NJH, Delamarre A, Michailoviene I, Marti MJ, van de Warrenburg BP, Meissner WG, Utkus A, Reinhard C, Graessner H, Tijssen MA
Eur J Neurol 2020 Aug;27(8):1493-1500. Epub 2020 Jun 19 doi: 10.1111/ene.14302. PMID: 32386078Free PMC Article
Singh YP, Pandey A, Vishwakarma S, Modi G
Mol Divers 2019 May;23(2):509-526. Epub 2018 Oct 6 doi: 10.1007/s11030-018-9878-4. PMID: 30293116

Recent clinical studies

Etiology

Amini E, Rohani M, Lang AE, Azad Z, Habibi SAH, Alavi A, Shahidi G, Emamikhah M, Chitsaz A
Mov Disord Clin Pract 2024 Jan;11(1):53-62. Epub 2023 Dec 1 doi: 10.1002/mdc3.13933. PMID: 38291840Free PMC Article
Lillian A, Zuo W, Laham L, Hilfiker S, Ye JH
Int J Mol Sci 2023 Apr 13;24(8) doi: 10.3390/ijms24087186. PMID: 37108349Free PMC Article
Dangel T, Kmieć T, Januszaniec A, Ważny B
Neurol Sci 2020 Mar;41(3):653-660. Epub 2019 Nov 22 doi: 10.1007/s10072-019-04099-5. PMID: 31758347Free PMC Article
Darling A, Aguilera-Albesa S, Tello CA, Serrano M, Tomás M, Camino-León R, Fernández-Ramos J, Jiménez-Escrig A, Poó P, O'Callaghan M, Ortez C, Nascimento A, Fernández Mesaque RC, Madruga M, Arrabal L, Roldan S, Gómez-Martín H, Garrido C, Temudo T, Jou-Muñoz C, Muchart J, Huisman TAGM, Poretti A, Lupo V, Espinós C, Pérez-Dueñas B
Parkinsonism Relat Disord 2019 Apr;61:179-186. Epub 2018 Oct 13 doi: 10.1016/j.parkreldis.2018.10.013. PMID: 30340910
Gitiaux C, Kaminska A, Boddaert N, Barcia G, Guéden S, The Tich SN, De Lonlay P, Quijano-Roy S, Hully M, Péréon Y, Desguerre I
Eur J Paediatr Neurol 2018 Sep;22(5):854-861. Epub 2018 May 22 doi: 10.1016/j.ejpn.2018.05.005. PMID: 29859652

Diagnosis

Emamikhah M, Saiyarsarai P, Schneider SA, Fasano A, Mohammadzadeh N, Rohani M
Can J Neurol Sci 2023 Jan;50(1):60-71. Epub 2022 Jan 24 doi: 10.1017/cjn.2021.502. PMID: 35067244
Belohlavkova A, Sterbova K, Betzler C, Burkhard S, Panzer A, Wolff M, Lassuthova P, Vlckova M, Kyncl M, Benova B, Jahodova A, Kudr M, Goerg M, Dusek P, Seeman P, Kluger G, Krsek P
Eur J Paediatr Neurol 2020 Sep;28:81-88. Epub 2020 Aug 4 doi: 10.1016/j.ejpn.2020.07.010. PMID: 32811771
Marshall RD, Collins A, Escolar ML, Jinnah HA, Klopstock T, Kruer MC, Videnovic A, Robichaux-Viehoever A, Burns C, Swett LL, Revicki DA, Bender RH, Lenderking WR
Orphanet J Rare Dis 2019 Jul 12;14(1):174. doi: 10.1186/s13023-019-1142-1. PMID: 31300018Free PMC Article
Gitiaux C, Kaminska A, Boddaert N, Barcia G, Guéden S, The Tich SN, De Lonlay P, Quijano-Roy S, Hully M, Péréon Y, Desguerre I
Eur J Paediatr Neurol 2018 Sep;22(5):854-861. Epub 2018 May 22 doi: 10.1016/j.ejpn.2018.05.005. PMID: 29859652
Khan AO, AlDrees A, Elmalik SA, Hassan HH, Michel M, Stevanin G, Azzedine H, Salih MA
Br J Ophthalmol 2014 Jul;98(7):889-93. doi: 10.1136/bjophthalmol-2013-304527. PMID: 24522175

Therapy

Lee S, Kovacs GG
Int J Mol Sci 2024 Apr 12;25(8) doi: 10.3390/ijms25084269. PMID: 38673855Free PMC Article
Bailey DK, Clark W, Kosman DJ
PLoS One 2021;16(7):e0254794. Epub 2021 Jul 26 doi: 10.1371/journal.pone.0254794. PMID: 34310628Free PMC Article
Apostolakis S, Kypraiou AM
Rev Neurosci 2017 Nov 27;28(8):893-911. doi: 10.1515/revneuro-2017-0020. PMID: 28792913
Stephenson E, Nathoo N, Mahjoub Y, Dunn JF, Yong VW
Nat Rev Neurol 2014 Aug;10(8):459-68. Epub 2014 Jul 8 doi: 10.1038/nrneurol.2014.118. PMID: 25002107
Lassmann H, van Horssen J, Mahad D
Nat Rev Neurol 2012 Nov 5;8(11):647-56. Epub 2012 Sep 25 doi: 10.1038/nrneurol.2012.168. PMID: 23007702

Prognosis

LeVine SM
Cells 2024 Apr 16;13(8) doi: 10.3390/cells13080689. PMID: 38667304Free PMC Article
Amini E, Rohani M, Lang AE, Azad Z, Habibi SAH, Alavi A, Shahidi G, Emamikhah M, Chitsaz A
Mov Disord Clin Pract 2024 Jan;11(1):53-62. Epub 2023 Dec 1 doi: 10.1002/mdc3.13933. PMID: 38291840Free PMC Article
De Vloo P, Lee DJ, Dallapiazza RF, Rohani M, Fasano A, Munhoz RP, Ibrahim GM, Hodaie M, Lozano AM, Kalia SK
Mov Disord 2019 Feb;34(2):264-273. Epub 2019 Jan 11 doi: 10.1002/mds.27563. PMID: 30633810
Darling A, Aguilera-Albesa S, Tello CA, Serrano M, Tomás M, Camino-León R, Fernández-Ramos J, Jiménez-Escrig A, Poó P, O'Callaghan M, Ortez C, Nascimento A, Fernández Mesaque RC, Madruga M, Arrabal L, Roldan S, Gómez-Martín H, Garrido C, Temudo T, Jou-Muñoz C, Muchart J, Huisman TAGM, Poretti A, Lupo V, Espinós C, Pérez-Dueñas B
Parkinsonism Relat Disord 2019 Apr;61:179-186. Epub 2018 Oct 13 doi: 10.1016/j.parkreldis.2018.10.013. PMID: 30340910
Jellinger KA
J Neural Transm Suppl 2002;(62):347-76. doi: 10.1007/978-3-7091-6139-5_33. PMID: 12456078

Clinical prediction guides

Ma J, Liu J, Chen S, Zhang W, Wang T, Cao M, Yang Y, Du Y, Cui G, Du Z
Front Biosci (Landmark Ed) 2024 Aug 20;29(8):291. doi: 10.31083/j.fbl2908291. PMID: 39206899
Lee S, Kovacs GG
Int J Mol Sci 2024 Apr 12;25(8) doi: 10.3390/ijms25084269. PMID: 38673855Free PMC Article
Sait H, Srivastava S, Pandey M, Ravichandran D, Shukla A, Mandal K, Saxena D, Shambhavi A, Majethia P, Rao LP, Sharma S, Phadke SR, Moirangthem A
Neurogenetics 2023 Apr;24(2):113-127. Epub 2023 Feb 15 doi: 10.1007/s10048-023-00712-0. PMID: 36790591
Darling A, Aguilera-Albesa S, Tello CA, Serrano M, Tomás M, Camino-León R, Fernández-Ramos J, Jiménez-Escrig A, Poó P, O'Callaghan M, Ortez C, Nascimento A, Fernández Mesaque RC, Madruga M, Arrabal L, Roldan S, Gómez-Martín H, Garrido C, Temudo T, Jou-Muñoz C, Muchart J, Huisman TAGM, Poretti A, Lupo V, Espinós C, Pérez-Dueñas B
Parkinsonism Relat Disord 2019 Apr;61:179-186. Epub 2018 Oct 13 doi: 10.1016/j.parkreldis.2018.10.013. PMID: 30340910
Apostolakis S, Kypraiou AM
Rev Neurosci 2017 Nov 27;28(8):893-911. doi: 10.1515/revneuro-2017-0020. PMID: 28792913

Recent systematic reviews

Emamikhah M, Saiyarsarai P, Schneider SA, Fasano A, Mohammadzadeh N, Rohani M
Can J Neurol Sci 2023 Jan;50(1):60-71. Epub 2022 Jan 24 doi: 10.1017/cjn.2021.502. PMID: 35067244

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