MPAN
MCID: MTC036
MIFTS: 25

Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN)

Categories: Rare diseases

Aliases & Classifications for Mitochondrial Membrane Protein-Associated Neurodegeneration

MalaCards integrated aliases for Mitochondrial Membrane Protein-Associated Neurodegeneration:

Name: Mitochondrial Membrane Protein-Associated Neurodegeneration 24 52 25
Neurodegeneration with Brain Iron Accumulation 4 52 25 71
Nbia4 24 52 25
Mpan 52 25
Mitochondrial Membrane Protein-Associated Neurodegeneration Due to C19orf12 Mutation 25
Neurodegeneration with Brain Iron Accumulation Due to C19orf12 Mutation 52
Neurodegeneration with Brain Iron Accumulation Type 4 52
Mitochondrial Protein-Associated Neurodegeneration 25
Nbia Due to C19orf12 Mutation 52

Classifications:



Summaries for Mitochondrial Membrane Protein-Associated Neurodegeneration

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 289560 Definition A rare neurodegenerative disorder characterized by iron accumulation in specific regions of the brain, usually the basal ganglia, and associated with slowly progressive pyramidal (spasticity ) and extrapyramidal (dystonia ) signs, motor axonal neuropathy, optic atrophy, cognitive decline, and neuropsychiatric abnormalities. Epidemiology Mitochondrial membrane protein -associated neurodegeneration (MPAN) is an extremely rare disease with an estimated worldwide prevalence of about 1/1,000,000. MPAN accounts for approximately 6-10% of cases neurodegeneration with brain iron accumulation (NBIA) cases, with less than 80 cases reported to date. Clinical description MPAN usually manifests during childhood (mean age: 10 years), but cases during adolescence or adulthood have been reported too. It presents with gait difficulty, dysarthria and bilateral optic atrophy. Early upper motor neuron signs (pyramidal signs, e.g. spasticity) are constant findings and are later followed by signs of lower motor neuron dysfunction (deep tendon reflex loss, muscular weakness and atrophy). Progressive dystonia, parkinsonism, cognitive decline, and neuropsychiatric symptoms are present in more than half of the patients. Weight loss and bowel and/or bladder dysfunction are common. Etiology MPAN is caused by mutations in the chromosome 19 open reading frame 12 gene (C19orf12 ; 19q13.11). A founder mutation (c.204_214del11 (p.Gly69ArgfsX10)) has been described in Eastern Europe. The function of C19orf12 remains uncertain, but it may be involved in mitochondrial function, lipid homeostasis and coenzyme A metabolism. Diagnostic methods Diagnosis is based on neuroimaging that shows evidence of iron deposits mainly in the globus pallidus and substantia nigra, often with unique T2-hyperintense streaking between the hypointense internal globus pallidus and external globus pallidus. Ophthalmologic examinations and evoked visual potentials are important to identify optic atrophy. Neuropathologic examination shows axonal spheroids, Lewy bodies and hyperphosphorylated tau-containing inclusions. Mutation analysis of the C19orf12 gene confirms the diagnosis. Differential diagnosis Differential diagnosis includes other NBIAs, more particularly fatty acid hydroxylase-associated neurodegeneration and PLA2G6-associated neurodegeneration. Spasticity, more prominent than dystonia, optic atrophy, motor neuropathy, and a slowly progressive course with cognitive decline help to differentiate MPAN from the other NBIAs. Antenatal diagnosis Prenatal diagnosis may be available for families in which disease-causing mutations have been identified in a previous affected sib. Genetic counseling MPAN is an autosomal recessive disorder. It is more common in consanguineous families or families of the same origin (i.e. both parents from the same small town). Parents of a patient with MPAN are obligate carriers . The risk of having an affected child in further pregnancies is of 25%. Management and treatment There is currently no curative treatment. Management strategies focus on the medical and surgical palliation of symptoms. Follow-up by a multidisciplinary team formed by neurologists , geneticists, ophthalmologists , physiotherapists, occupational therapists , speech and language therapists, orthopedic surgeons, and neurosurgeons is essential. Prognosis The progression of MPAN is usually slow and may lead to loss of independent ambulation due to spasticity, dystonia and parkinsonism; limited communication due to dysarthria and cognitive decline; and severe dementia . Life expectancy is variable. Premature death may occur due to secondary complications such as aspiration pneumonia. Visit the Orphanet disease page for more resources.

MalaCards based summary : Mitochondrial Membrane Protein-Associated Neurodegeneration, also known as neurodegeneration with brain iron accumulation 4, is related to neurodegeneration with brain iron accumulation 4 and neurodegeneration with brain iron accumulation, and has symptoms including ataxia, tremor and abnormality of extrapyramidal motor function. An important gene associated with Mitochondrial Membrane Protein-Associated Neurodegeneration is C19orf12 (Chromosome 19 Open Reading Frame 12). Affiliated tissues include brain, eye and globus pallidus, and related phenotypes are behavioral abnormality and muscle weakness

Genetics Home Reference : 25 Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a disorder of the nervous system. The condition typically begins in childhood or early adulthood and worsens (progresses) over time. MPAN commonly begins with difficulty walking. As the condition progresses, affected individuals usually develop other movement problems, including muscle stiffness (spasticity) and involuntary muscle cramping (dystonia). Many people with MPAN have a pattern of movement abnormalities known as parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, involuntary trembling (tremors), and an inability to hold the body upright and balanced (postural instability). Other neurological problems that occur in individuals with MPAN include degeneration of the nerve cells that carry visual information from the eyes to the brain (optic atrophy), which can impair vision; problems with speech (dysarthria); difficulty swallowing (dysphagia); and, in later stages of the condition, an inability to control the bowels or the flow of urine (incontinence). Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, mood swings, hyperactivity, and depression. MPAN is characterized by an abnormal buildup of iron in certain regions of the brain. Because of these deposits, MPAN is considered part of a group of conditions known as neurodegeneration with brain iron accumulation (NBIA).

GeneReviews: NBK185329

Related Diseases for Mitochondrial Membrane Protein-Associated Neurodegeneration

Diseases related to Mitochondrial Membrane Protein-Associated Neurodegeneration via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 30)
# Related Disease Score Top Affiliating Genes
1 neurodegeneration with brain iron accumulation 4 12.2
2 neurodegeneration with brain iron accumulation 10.6
3 3-methylglutaconic aciduria, type iii 10.3
4 dystonia 10.3
5 neuropathy 10.2
6 neurodegeneration with brain iron accumulation 1 10.2
7 autosomal recessive disease 10.2
8 axonal neuropathy 10.2
9 ataxia and polyneuropathy, adult-onset 10.1
10 spastic paraplegia 43, autosomal recessive 10.1
11 spastic ataxia 10.1
12 hereditary spastic paraplegia 10.1
13 movement disease 10.1
14 hereditary dystonia 10.1
15 amyotrophic lateral sclerosis 1 10.0
16 retinitis pigmentosa 10.0
17 aphasia 10.0
18 neuroretinitis 10.0
19 lateral sclerosis 10.0
20 motor neuron disease 10.0
21 retinitis 10.0
22 paraplegia 10.0
23 juvenile amyotrophic lateral sclerosis 10.0
24 pseudobulbar affect 10.0
25 dysphagia 10.0
26 hypotonia 10.0
27 spasticity 10.0
28 posttransplant acute limbic encephalitis 10.0
29 hydrocephalus 10.0
30 myoclonus 10.0

Graphical network of the top 20 diseases related to Mitochondrial Membrane Protein-Associated Neurodegeneration:



Diseases related to Mitochondrial Membrane Protein-Associated Neurodegeneration

Symptoms & Phenotypes for Mitochondrial Membrane Protein-Associated Neurodegeneration

Human phenotypes related to Mitochondrial Membrane Protein-Associated Neurodegeneration:

31 (show all 24)
# Description HPO Frequency HPO Source Accession
1 behavioral abnormality 31 hallmark (90%) HP:0000708
2 muscle weakness 31 hallmark (90%) HP:0001324
3 dysarthria 31 hallmark (90%) HP:0001260
4 mental deterioration 31 hallmark (90%) HP:0001268
5 babinski sign 31 hallmark (90%) HP:0003487
6 rigidity 31 hallmark (90%) HP:0002063
7 postural instability 31 hallmark (90%) HP:0002172
8 hand tremor 31 hallmark (90%) HP:0002378
9 optic atrophy 31 frequent (33%) HP:0000648
10 dysphagia 31 frequent (33%) HP:0002015
11 bowel incontinence 31 frequent (33%) HP:0002607
12 dystonia 31 frequent (33%) HP:0001332
13 hyperactive deep tendon reflexes 31 frequent (33%) HP:0006801
14 frequent falls 31 frequent (33%) HP:0002359
15 spastic paraparesis 31 frequent (33%) HP:0002313
16 urinary incontinence 31 frequent (33%) HP:0000020
17 motor axonal neuropathy 31 frequent (33%) HP:0007002
18 parkinsonism 31 frequent (33%) HP:0001300
19 bradykinesia 31 frequent (33%) HP:0002067
20 abnormal globus pallidus morphology 31 frequent (33%) HP:0002453
21 abnormality of the substantia nigra 31 frequent (33%) HP:0045007
22 shuffling gait 31 occasional (7.5%) HP:0002362
23 abnormal saccadic eye movements 31 occasional (7.5%) HP:0000570
24 respiratory insufficiency 31 very rare (1%) HP:0002093

UMLS symptoms related to Mitochondrial Membrane Protein-Associated Neurodegeneration:


ataxia, tremor, abnormality of extrapyramidal motor function, oromandibular dystonia, muscle spasticity, abnormal pyramidal signs

Drugs & Therapeutics for Mitochondrial Membrane Protein-Associated Neurodegeneration

Search Clinical Trials , NIH Clinical Center for Mitochondrial Membrane Protein-Associated Neurodegeneration

Genetic Tests for Mitochondrial Membrane Protein-Associated Neurodegeneration

Anatomical Context for Mitochondrial Membrane Protein-Associated Neurodegeneration

MalaCards organs/tissues related to Mitochondrial Membrane Protein-Associated Neurodegeneration:

40
Brain, Eye, Globus Pallidus

Publications for Mitochondrial Membrane Protein-Associated Neurodegeneration

Articles related to Mitochondrial Membrane Protein-Associated Neurodegeneration:

(show all 41)
# Title Authors PMID Year
1
Rapid disease progression in adult-onset mitochondrial membrane protein-associated neurodegeneration. 61 24
23278385 2013
2
Mitochondrial membrane protein associated neurodegenration: a novel variant of neurodegeneration with brain iron accumulation. 61 24
23436634 2013
3
New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN. 24 61
23269600 2013
4
Mitochondrial membrane protein-associated neurodegeneration (MPAN). 24 61
24209434 2013
5
C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis. 61 24
22584950 2012
6
A novel frameshift mutation of C19ORF12 causes NBIA4 with cerebellar atrophy and manifests with severe peripheral motor axonal neuropathy. 24
23521069 2014
7
Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12. 24
23857908 2013
8
Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. 24
21981780 2011
9
Iron-related MRI images in patients with pantothenate kinase-associated neurodegeneration (PKAN) treated with deferiprone: results of a phase II pilot trial. 24
21557313 2011
10
Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN). 24
18443314 2008
11
Brain iron and metabolic abnormalities in C19orf12 mutation carriers: A 7.0 tesla MRI study in mitochondrial membrane protein-associated neurodegeneration. 61
31518459 2020
12
Late-Onset Mitochondrial Membrane Protein-Associated Neurodegeneration With Extensive Brain Iron Deposition. 61
31970231 2020
13
[Pedigree analysis of C19ORF12 p.Asp18Tyr mutation in a family with mitochondrial membrane protein associated neurodegeneration]. 61
31607023 2019
14
A Novel Mutation in Neurodegeneration with Brain Iron Accumulation - A Case Report. 61
31744972 2019
15
Mitochondrial Membrane Protein Associated Neurodegeneration   (MPAN) with a Novel C19orf12 Mutation in the First Decade of Life. 61
30825065 2019
16
Autosomal dominant mitochondrial membrane protein-associated neurodegeneration (MPAN). 61
31087512 2019
17
Levodopa-induced dyskinesias in mitochondrial membrane protein-associated neurodegeneration. 61
30859014 2019
18
Clinical and genetic spectrum of an orphan disease MPAN: a series with new variants and a novel phenotype. 61
31804703 2019
19
Novel case of neurodegeneration with brain iron accumulation 4 (NBIA4) caused by a pathogenic variant affecting splicing. 61
30392167 2018
20
Transcranial Sonography in Mitochondrial Membrane Protein-Associated Neurodegeneration. 61
28352978 2018
21
Mitochondrial membrane protein-associated neurodegeneration: a case report and literature review. 61
30088953 2018
22
Neurodegeneration with brain iron accumulation. 61
29325618 2018
23
The p.Thr11Met mutation in c19orf12 is frequent among adult Turkish patients with MPAN. 61
28347615 2017
24
Evolution and novel radiological changes of neurodegeneration associated with mutations in C19orf12. 61
28347614 2017
25
Mitochondrial membrane protein-associated neurodegeneration. 61
28359667 2017
26
A Novel Deletion Mutation of Exon 2 of the C19orf12 Gene in an Omani Family with Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN). 61
28042406 2017
27
Retinal and optic nerve abnormalities in neurodegeneration associated with mutations in C19orf12 (MPAN). 61
27772766 2016
28
Mitochondrial Membrane Protein-Associated Neurodegeneration Mimicking Juvenile Amyotrophic Lateral Sclerosis. 61
27671242 2016
29
Clinical and imaging characteristics of late onset mitochondrial membrane protein-associated neurodegeneration (MPAN). 61
27801611 2016
30
Movement disorders in mitochondrial diseases. 61
27476418 2016
31
A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging. 61
27487380 2016
32
Mitochondrial membrane protein-associated neurodegeneration in a Turkish patient. 61
27857812 2016
33
"Eye of tiger sign" mimic in an adolescent boy with mitochondrial membrane protein associated neurodegeneration (MPAN). 61
26602591 2016
34
Behr syndrome with homozygous C19ORF12 mutation. 61
26187298 2015
35
Mitochondrial Membrane Protein-Associated Neurodegeneration. 61
26231266 2015
36
C19orf12 gene mutations in patients with neurodegeneration with brain iron accumulation. 61
25962551 2015
37
Eye of the tiger sign in a 23 year patient with mitochondrial membrane protein associated neurodegeneration. 61
25819119 2015
38
Analysis of the C19orf12 and WDR45 genes in patients with neurodegeneration with brain iron accumulation. 61
25592411 2015
39
Brain iron quantification by MRI in mitochondrial membrane protein-associated neurodegeneration under iron-chelating therapy. 61
25574478 2014
40
Mitochondrial Membrane Protein-Associated Neurodegeneration 61
24575447 2014
41
Transcranial sonography in mitochondrial membrane protein-associated neurodegeneration. 61
23871464 2013

Variations for Mitochondrial Membrane Protein-Associated Neurodegeneration

Expression for Mitochondrial Membrane Protein-Associated Neurodegeneration

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Pathways for Mitochondrial Membrane Protein-Associated Neurodegeneration

GO Terms for Mitochondrial Membrane Protein-Associated Neurodegeneration

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