MCID: MTC036
MIFTS: 25

Mitochondrial Membrane Protein-Associated Neurodegeneration

Categories: Rare diseases, Neuronal 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 53 25
Neurodegeneration with Brain Iron Accumulation 4 53 25 73
Nbia4 24 53 25
Mpan 53 25
Mitochondrial Membrane Protein-Associated Neurodegeneration Due to C19orf12 Mutation 25
Neurodegeneration with Brain Iron Accumulation Due to C19orf12 Mutation 53
Neurodegeneration with Brain Iron Accumulation Type 4 53
Mitochondrial Protein-Associated Neurodegeneration 25
Nbia Due to C19orf12 Mutation 53

Classifications:



Summaries for Mitochondrial Membrane Protein-Associated Neurodegeneration

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 289560Disease definitionMitochondrial membrane protein-sssociated neurodegeneration (MPAN), also known as neurogeneration with brain iron accumulation (NBIA) due to C19orf12 mutations, is an autosomal recessive 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.EpidemiologyMPAN is an extremely rare disease with an estimated worldwide prevalence of about 1/1,000,000. MPAN accounts for approximately 30% of cases NBIA cases, with less than 80 cases reported to date.Clinical descriptionMPAN usually manifests during childhood (mean age: 10 years) 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.EtiologyMPAN 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 methodsDiagnosis 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 diagnosisDifferential diagnosis includes other NBIAs, more particularly fatty acid hydroxylase-associated neurodegeneration and PLA2G6-associated neurodegeneration (see these terms). 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 diagnosisPrenatal diagnosis may be available for families in which disease-causing mutations have been identified in a previous affected sib.Genetic counselingMPAN 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 treatmentThere 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.PrognosisThe 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 has symptoms including ataxia, muscle spasticity and tremor. An important gene associated with Mitochondrial Membrane Protein-Associated Neurodegeneration is C19orf12 (Chromosome 19 Open Reading Frame 12). Affiliated tissues include brain, globus pallidus and eye, and related phenotypes are urinary incontinence and abnormality of saccadic eye movements

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.

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:

# Related Disease Score Top Affiliating Genes
1 neurodegeneration with brain iron accumulation 4 11.6

Symptoms & Phenotypes for Mitochondrial Membrane Protein-Associated Neurodegeneration

Human phenotypes related to Mitochondrial Membrane Protein-Associated Neurodegeneration:

32 (show all 24)
# Description HPO Frequency HPO Source Accession
1 urinary incontinence 32 frequent (33%) HP:0000020
2 abnormality of saccadic eye movements 32 occasional (7.5%) HP:0000570
3 optic atrophy 32 frequent (33%) HP:0000648
4 behavioral abnormality 32 hallmark (90%) HP:0000708
5 dysarthria 32 hallmark (90%) HP:0001260
6 mental deterioration 32 hallmark (90%) HP:0001268
7 parkinsonism 32 frequent (33%) HP:0001300
8 muscle weakness 32 hallmark (90%) HP:0001324
9 dystonia 32 frequent (33%) HP:0001332
10 dysphagia 32 frequent (33%) HP:0002015
11 rigidity 32 hallmark (90%) HP:0002063
12 bradykinesia 32 frequent (33%) HP:0002067
13 respiratory insufficiency 32 very rare (1%) HP:0002093
14 postural instability 32 hallmark (90%) HP:0002172
15 spastic paraparesis 32 frequent (33%) HP:0002313
16 frequent falls 32 frequent (33%) HP:0002359
17 shuffling gait 32 occasional (7.5%) HP:0002362
18 hand tremor 32 hallmark (90%) HP:0002378
19 abnormal globus pallidus morphology 32 frequent (33%) HP:0002453
20 bowel incontinence 32 frequent (33%) HP:0002607
21 babinski sign 32 hallmark (90%) HP:0003487
22 hyperactive deep tendon reflexes 32 frequent (33%) HP:0006801
23 motor axonal neuropathy 32 frequent (33%) HP:0007002
24 abnormality of the substantia nigra 32 frequent (33%) HP:0045007

UMLS symptoms related to Mitochondrial Membrane Protein-Associated Neurodegeneration:


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

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:

41
Brain, Globus Pallidus, Eye

Publications for Mitochondrial Membrane Protein-Associated Neurodegeneration

Articles related to Mitochondrial Membrane Protein-Associated Neurodegeneration:

(show all 14)
# Title Authors Year
1
Transcranial Sonography in Mitochondrial Membrane Protein-Associated Neurodegeneration. ( 28352978 )
2017
2
Mitochondrial membrane protein-associated neurodegeneration. ( 28359667 )
2017
3
A Novel Deletion Mutation of Exon 2 of the C19orf12 Gene in an Omani Family with Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN). ( 28042406 )
2017
4
"Eye of tiger sign" mimic in an adolescent boy with mitochondrial membrane protein associated neurodegeneration (MPAN). ( 26602591 )
2016
5
Mitochondrial membrane protein-associated neurodegeneration in a Turkish patient. ( 27857812 )
2016
6
Clinical and imaging characteristics of late onset mitochondrial membrane protein-associated neurodegeneration (MPAN). ( 27801611 )
2016
7
Mitochondrial Membrane Protein-Associated Neurodegeneration Mimicking Juvenile Amyotrophic LateralA Sclerosis. ( 27671242 )
2016
8
Eye of the tiger sign in a 23year patient with mitochondrial membrane protein associated neurodegeneration. ( 25819119 )
2015
9
Mitochondrial Membrane Protein-Associated Neurodegeneration. ( 26231266 )
2015
10
Brain iron quantification by MRI in mitochondrial membrane protein-associated neurodegeneration under iron-chelating therapy. ( 25574478 )
2014
11
Rapid disease progression in adult-onset mitochondrial membrane protein-associated neurodegeneration. ( 23278385 )
2013
12
Transcranial sonography in mitochondrial membrane protein-associated neurodegeneration. ( 23871464 )
2013
13
Mitochondrial membrane protein-associated neurodegeneration (MPAN). ( 24209434 )
2013
14
Mitochondrial Membrane Protein-Associated Neurodegeneration ( 24575447 )
1993

Variations for Mitochondrial Membrane Protein-Associated Neurodegeneration

Expression for Mitochondrial Membrane Protein-Associated Neurodegeneration

Search GEO for disease gene expression data for Mitochondrial Membrane Protein-Associated Neurodegeneration.

Pathways for Mitochondrial Membrane Protein-Associated Neurodegeneration

GO Terms for Mitochondrial Membrane Protein-Associated Neurodegeneration

Sources for Mitochondrial Membrane Protein-Associated Neurodegeneration

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