U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Neuroferritinopathy(NBIA3)

MedGen UID:
381211
Concept ID:
C1853578
Disease or Syndrome
Synonyms: BASAL GANGLIA DISEASE, ADULT-ONSET; NBIA3; Neurodegeneration with brain iron accumulation 3
SNOMED CT: Adult onset basal ganglia disease (699299001); Ferritin related neurodegeneration (699299001); Neuroferritinopathy (699299001)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): FTL (19q13.33)
 
Monarch Initiative: MONDO:0011638
OMIM®: 606159
Orphanet: ORPHA157846

Definition

Neuroferritinopathy is an adult-onset progressive movement disorder characterized by chorea or dystonia and speech and swallowing deficits. The movement disorder typically affects one or two limbs and progresses to become more generalized within 20 years of disease onset. When present, asymmetry in the movement abnormalities remains throughout the course of the disorder. Most individuals develop a characteristic orofacial action-specific dystonia related to speech that leads to dysarthrophonia. Frontalis overactivity and orolingual dyskinesia are common. Cognitive deficits and behavioral issues become major problems with time. [from GeneReviews]

Additional descriptions

From OMIM
Neurodegeneration with brain iron accumulation is a genetically heterogeneous disorder characterized by progressive iron accumulation in the basal ganglia and other regions of the brain, resulting in extrapyramidal movements, such as parkinsonism and dystonia. Age at onset, cognitive involvement, and mode of inheritance is variable (review by Gregory et al., 2009).  http://www.omim.org/entry/606159
From MedlinePlus Genetics
Neuroferritinopathy is a disorder in which iron gradually accumulates in the brain. Certain brain regions that help control movement (basal ganglia) are particularly affected. People with neuroferritinopathy have progressive problems with movement that begin at about age 40. These movement problems can include involuntary jerking motions (chorea), rhythmic shaking (tremor), difficulty coordinating movements (ataxia), or uncontrolled tensing of muscles (dystonia). Symptoms of the disorder may be more apparent on one side of the body than on the other. Affected individuals may also have difficulty swallowing (dysphagia) and speaking (dysarthria).

Intelligence is unaffected in most people with neuroferritinopathy, but some individuals develop a gradual decline in thinking and reasoning abilities (dementia). Personality changes such as reduced inhibitions and difficulty controlling emotions may also occur as the disorder progresses.  https://medlineplus.gov/genetics/condition/neuroferritinopathy

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
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).
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Mutism
MedGen UID:
6476
Concept ID:
C0026884
Disease or Syndrome
Inability to speak or communicate verbally past the age of typical language development.
Neurodegeneration
MedGen UID:
17999
Concept ID:
C0027746
Cell or Molecular Dysfunction
Progressive loss of neural cells and tissue.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Writer cramp
MedGen UID:
57821
Concept ID:
C0154676
Disease or Syndrome
A focal dystonia of the fingers, hand, and/or forearm that appears when the affected person attempts to do a task that requires fine motor movements such as writing or playing a musical instrument.
Bradykinesia
MedGen UID:
115925
Concept ID:
C0233565
Sign or Symptom
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
Anarthria
MedGen UID:
68604
Concept ID:
C0234517
Disease or Syndrome
A defect in the motor ability that enables speech.
Micrographia
MedGen UID:
66806
Concept ID:
C0240341
Finding
Abnormally small-sized handwriting is formally defined as an impairment of fine motor skills, which mainly manifests as a progressive or stable reduction in amplitude during a writing task.
Parkinsonism
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Disinhibition
MedGen UID:
633911
Concept ID:
C0474398
Finding
Reduced ability to control, or a failure to resist a temptation, urge, or impulse. Examples include disregard for social conventions, general impulsivity, and poor risk assessment.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Laryngeal dystonia
MedGen UID:
409603
Concept ID:
C1963946
Disease or Syndrome
A form of focal dystonia that affects the vocal cords, associated with involuntary contractions of the vocal cords causing interruptions of speech and affecting the voice quality and often leading to patterned, repeated breaks in speech.
Subcortical dementia
MedGen UID:
870488
Concept ID:
C4024935
Disease or Syndrome
A particular type of dementia characterized by a pattern of mental defects consisting prominently of forgetfulness, slowness of thought processes, and personality or mood change.
Cavitation of the basal ganglia
MedGen UID:
870505
Concept ID:
C4024952
Disease or Syndrome
The formation of small cavities in the tissue of the basal ganglia.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Decreased circulating ferritin concentration
MedGen UID:
66021
Concept ID:
C0241012
Finding
Abnormally reduced concentration of ferritin, a ubiquitous intracellular protein that stores iron, in the blood.
Dysphonia
MedGen UID:
282893
Concept ID:
C1527344
Mental or Behavioral Dysfunction
Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause.
Blepharospasm
MedGen UID:
599
Concept ID:
C0005747
Disease or Syndrome
A focal dystonia that affects the muscles of the eyelids and brow, associated with involuntary recurrent spasm of both eyelids.
Hypomimic face
MedGen UID:
208827
Concept ID:
C0813217
Finding
A reduced degree of motion of the muscles beneath the skin of the face, often associated with reduced facial crease formation.

Professional guidelines

PubMed

Cardoso F
Neurodegener Dis Manag 2014;4(1):67-72. doi: 10.2217/nmt.13.78. PMID: 24640980

Recent clinical studies

Etiology

Marchand F, Moreau C, Kuchcinski G, Huin V, Defebvre L, Devos D
Mov Disord 2022 Sep;37(9):1948-1952. Epub 2022 Aug 22 doi: 10.1002/mds.29145. PMID: 35996824Free PMC Article
Dusek P, Hofer T, Alexander J, Roos PM, Aaseth JO
Biomolecules 2022 May 17;12(5) doi: 10.3390/biom12050714. PMID: 35625641Free PMC Article
Jellinger KA
J Neural Transm (Vienna) 2022 Jun;129(5-6):521-543. Epub 2021 Aug 7 doi: 10.1007/s00702-021-02392-2. PMID: 34363531
Cozzi A, Santambrogio P, Ripamonti M, Rovida E, Levi S
Cell Mol Life Sci 2021 Apr;78(7):3355-3367. Epub 2021 Jan 13 doi: 10.1007/s00018-020-03747-w. PMID: 33439270
Dusek P, Jankovic J, Le W
Neurobiol Dis 2012 Apr;46(1):1-18. Epub 2012 Jan 12 doi: 10.1016/j.nbd.2011.12.054. PMID: 22266337

Diagnosis

Dusek P, Hofer T, Alexander J, Roos PM, Aaseth JO
Biomolecules 2022 May 17;12(5) doi: 10.3390/biom12050714. PMID: 35625641Free PMC Article
Cozzi A, Santambrogio P, Ripamonti M, Rovida E, Levi S
Cell Mol Life Sci 2021 Apr;78(7):3355-3367. Epub 2021 Jan 13 doi: 10.1007/s00018-020-03747-w. PMID: 33439270
Woimant F, Trocello JM
Handb Clin Neurol 2014;120:851-64. doi: 10.1016/B978-0-7020-4087-0.00057-7. PMID: 24365357
Lehn A, Boyle R, Brown H, Airey C, Mellick G
Parkinsonism Relat Disord 2012 Sep;18(8):909-15. Epub 2012 Jul 17 doi: 10.1016/j.parkreldis.2012.06.021. PMID: 22818529
Schneider SA, Bhatia KP
Handb Clin Neurol 2011;100:101-12. doi: 10.1016/B978-0-444-52014-2.00005-7. PMID: 21496572

Therapy

Marchand F, Moreau C, Kuchcinski G, Huin V, Defebvre L, Devos D
Mov Disord 2022 Sep;37(9):1948-1952. Epub 2022 Aug 22 doi: 10.1002/mds.29145. PMID: 35996824Free PMC Article
Tarnacka B, Jopowicz A, Maślińska M
Int J Mol Sci 2021 Jul 22;22(15) doi: 10.3390/ijms22157820. PMID: 34360586Free PMC Article
Qian ZM, Ke Y
Med Res Rev 2020 Mar;40(2):633-653. Epub 2019 Aug 30 doi: 10.1002/med.21631. PMID: 31471929
Tang M, Chen Z, Wu D, Chen L
J Cell Physiol 2018 Dec;233(12):9179-9190. Epub 2018 Aug 4 doi: 10.1002/jcp.26954. PMID: 30076709
Garringer HJ, Irimia JM, Li W, Goodwin CB, Richine B, Acton A, Chan RJ, Peacock M, Muhoberac BB, Ghetti B, Vidal R
PLoS One 2016;11(8):e0161341. Epub 2016 Aug 30 doi: 10.1371/journal.pone.0161341. PMID: 27574973Free PMC Article

Prognosis

Turner S, Dress C, Misra VK
Eur J Med Genet 2021 Mar;64(3):104159. Epub 2021 Feb 4 doi: 10.1016/j.ejmg.2021.104159. PMID: 33548513
Castiglioni E, Finazzi D, Goldwurm S, Levi S, Pezzoli G, Garavaglia B, Nardocci N, Malcovati L, Porta MG, Gallì A, Forni GL, Girelli D, Maccarinelli F, Poli M, Ferrari M, Cremonesi L, Arosio P
Genet Test Mol Biomarkers 2010 Dec;14(6):793-6. Epub 2010 Oct 12 doi: 10.1089/gtmb.2010.0076. PMID: 20939738
Chinnery PF, Crompton DE, Birchall D, Jackson MJ, Coulthard A, Lombès A, Quinn N, Wills A, Fletcher N, Mottershead JP, Cooper P, Kellett M, Bates D, Burn J
Brain 2007 Jan;130(Pt 1):110-9. Epub 2006 Dec 2 doi: 10.1093/brain/awl319. PMID: 17142829
Mir P, Edwards MJ, Curtis AR, Bhatia KP, Quinn NP
Mov Disord 2005 Feb;20(2):243-5. doi: 10.1002/mds.20280. PMID: 15390032
Crompton DE, Chinnery PF, Fey C, Curtis AR, Morris CM, Kierstan J, Burt A, Young F, Coulthard A, Curtis A, Ince PG, Bates D, Jackson MJ, Burn J
Blood Cells Mol Dis 2002 Nov-Dec;29(3):522-31. doi: 10.1006/bcmd.2002.0589. PMID: 12547246

Clinical prediction guides

Dusek P, Hofer T, Alexander J, Roos PM, Aaseth JO
Biomolecules 2022 May 17;12(5) doi: 10.3390/biom12050714. PMID: 35625641Free PMC Article
Yévenes A
Subcell Biochem 2017;83:75-102. doi: 10.1007/978-3-319-46503-6_3. PMID: 28271473
Keogh MJ, Aribisala BS, He J, Tulip E, Butteriss D, Morris C, Gorman G, Horvath R, Chinnery PF, Blamire AM
J Neurol 2015 Oct;262(10):2232-40. Epub 2015 Jul 4 doi: 10.1007/s00415-015-7832-2. PMID: 26142024Free PMC Article
Rouault TA
Nat Rev Neurosci 2013 Aug;14(8):551-64. Epub 2013 Jul 3 doi: 10.1038/nrn3453. PMID: 23820773
Batista-Nascimento L, Pimentel C, Menezes RA, Rodrigues-Pousada C
Oxid Med Cell Longev 2012;2012:128647. Epub 2012 May 30 doi: 10.1155/2012/128647. PMID: 22701145Free PMC Article

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...