MCID: ATX029
MIFTS: 43

Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Metabolic diseases

Aliases & Classifications for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

MalaCards integrated aliases for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

Name: Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia 53 13 69
Aoa1 53 23 49 55 71
Eoca-Ha 53 49 71 51
Eaoh 53 49 24 71
Ataxia with Oculomotor Apraxia Type 1 12 23 14
Ataxia-Telangiectasia-Like Syndrome 53 49 36
Ataxia-Oculomotor Apraxia 1 53 49 71
Adult Onset Ataxia with Oculomotor Apraxia 24 28
Ataxia-Oculomotor Apraxia Syndrome 53 71
Ataxia-Oculomotor Apraxia Type 1 49 55
Aoa 53 71
Early-Onset Ataxia with Ocular Motor Apraxia and Hypoalbuminemia 24
Early-Onset Ataxia with Oculomotor Apraxia and Hypoalbuminemia 49
Ataxia Early-Onset with Oculomotor Apraxia and Hypoalbuminemia 71
Cerebellar Ataxia, Early-Onset, with Hypoalbuminemia; Eoca-Ha 53
Spinocerebellar Ataxia, Recessive, Non-Friedreich Type 1 24
Cerebellar Ataxia, Early-Onset, with Hypoalbuminemia 53
Spinocerebellar Ataxia with Axonal Neuropathy Type 2 24
Early-Onset Cerebellar Ataxia with Hypoalbuminemia 49
Cerebellar Ataxia Early-Onset with Hypoalbuminemia 71
Spinocerebellar Ataxia, Autosomal Recessive 1 69
Ataxia-Oculomotor Apraxia Syndrome; Aoa 53
Ataxia-Oculomotor Apraxia 1; Aoa1 53
Ataxia with Oculomotor Apraxia 24
Scar1 24
Scan2 24

Characteristics:

Orphanet epidemiological data:

55
ataxia-oculomotor apraxia type 1
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset is usually in childhood or adolescence (2 to 18 years)
adult onset has been reported
oculomotor apraxia is not always present


HPO:

31
ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia:
Onset and clinical course adult onset juvenile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1168Disease definitionAtaxia with oculomotor apraxia type 1 (AOA1) is a rare autosomal recessive cerebellar ataxia (ARCA; see this term), characterized by progressive cerebellar ataxia associated with oculomotor apraxia, severe neuropathy, and hypoalbuminemia.EpidemiologyAOA1 represents 3.6% of all ARCA in Portugal; in Japan, AOA1 seems to be the most frequent cause of ARCA. In a cohort of 227 patients mostly of French origin with progressive cerebellar ataxia selected after exclusion of Friedreich ataxia (see this term), the relative frequency of AOA1 was of 5%.Clinical descriptionCerebellar ataxia is the first manifestation of AOA1 with a mean age of onset of 4.3 years (2-10 years) and is characterized by progressive gait imbalance followed by dysarthria, and limb dysmetria. Later, peripheral axonal motor neuropathy dominates the clinical picture. Oculomotor apraxia (OMA; inability to coordinate eyes ± head movements: when the head turns toward a lateral target; the head reaches the target before the eyes) is present in almost all individuals with AOA1. Chorea is present at onset in 80% of patients and upper limb dystonia (see this term) occurs in about 50% of individuals. Additional features include square wave jerks, saccadic pursuit and gaze-evoked nystagmus, areflexia followed by severe peripheral neuropathy. Variable intellectual disability is observed.EtiologyAOA1 results from mutations in APTX gene (9p13.3) encoding aprataxin which plays a role in DNA-single-strand break repair. Most mutations identified so far are localized in exons 5, 6 and 7. Some correlations between genotype and phenotype have been established: for example severe and persistent choreic phenotype is associated with mutations A198V; truncating mutations are associated with earlier onset and deletions with more severe phenotype and intellectual disability.Diagnostic methodsDiagnosis of AOA1 is based on the clinical features, the progressive evolution, the absence of extraneurologic findings and family history. Electromyography findings reveal severe axonal sensory-motor neuropathy. Oculographic recordings demonstrate normal latencies, hypometric saccades, decrease mean gain in amplitude and broken saccades into multiple successive saccades. Cerebral magnetic resonance imagery displays cerebellar atrophy. Hypoalbuminemia and hypercholesterolemia are usual (disease duration is positively correlated with cholesterol and negatively correlated with albumin levels). Diagnosis is confirmed by molecular analysis of APTX gene.Differential diagnosisDifferential diagnosis includes Friedreich ataxia, ataxia with vitamin E deficiency, AOA2, ataxia-telangiectasia, ataxia-telangiectasia-like disorder, autosomal recessive spastic ataxia of Charlevoix-Saguenay (see these terms).Antenatal diagnosisCarrier testing for at-risk family members and prenatal testing are possible if both disease-causing alleles in a family are known.Genetic counselingTransmission of AOA1 is autosomal recessive. Genetic counseling is recommended as each sib of an affected individual has 25% chance of being affected, 50% chance of being an asymptomatic carrier, and 25% chance of being neither affected nor a carrier.Management and treatmentNo specific treatment exists for AOA1 and management is mainly supportive. It includes physical therapy for cerebellar ataxia and disabilities resulting from peripheral neuropathy; educational support for reading and writing difficulties, speech therapy for dysarthria and cognitive impairment. Low-cholesterol diet and hypolipemiant treatment are recommended. Routine follow-up with a neurologist or neurogenetician is suggested. Some therapeutic trials are on the way such as the evaluation of efficacy of Coenzyme Q10 in evolution of the disease.PrognosisAOA1 is a progressive neurodegenerative disorder and most patients usually become wheelchair bound from seven to ten years after onset of the disease.Visit the Orphanet disease page for more resources. Last updated: 1/1/2015

MalaCards based summary : Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia, also known as aoa1, is related to spinocerebellar ataxia, autosomal recessive 1 and apraxia, and has symptoms including ataxia, gait disturbance and peripheral neuropathy. An important gene associated with Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia is APTX (Aprataxin), and among its related pathways/superpathways are Base excision repair and Nucleotide excision repair. The drugs Ethanol and Coenzyme Q10 have been mentioned in the context of this disorder. Affiliated tissues include eye and testes, and related phenotype is Increased viability with MLN4924 (a NAE inhibitor).

OMIM : 53 Ataxia-oculomotor apraxia syndrome is an early-onset autosomal recessive cerebellar ataxia with peripheral axonal neuropathy, oculomotor apraxia (defined as the limitation of ocular movements on command), and hypoalbuminemia (Moreira et al., 2001). (208920)

UniProtKB/Swiss-Prot : 71 Ataxia-oculomotor apraxia syndrome: An autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy.

Genetics Home Reference : 24 Ataxia with oculomotor apraxia is a condition characterized by progressive problems with movement. The hallmark of this condition is difficulty coordinating movements (ataxia), which is often the first symptom. Most affected people also have oculomotor apraxia, which makes it difficult to move their eyes side-to-side. People with oculomotor apraxia have to turn their head to see things in their side (peripheral) vision.

GeneReviews: NBK1456

Related Diseases for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Graphical network of the top 20 diseases related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:



Diseases related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Symptoms & Phenotypes for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Symptoms via clinical synopsis from OMIM:

53
NeurologicCentralNervousSystem:
tremor
dystonia
gait ataxia
dysarthria
limb ataxia
more
SkeletalSpine:
scoliosis

HeadAndNeckEyes:
progressive external ophthalmoplegia
gaze-evoked nystagmus
oculomotor apraxia (in 86% of patients)
hypometric saccades

LaboratoryAbnormalities:
hypoalbuminemia (in 83%)
hypercholesterolemia (in 75%)

MuscleSoftTissue:
muscle weakness
distal muscular atrophy due to peripheral neuropathy
muscle coenzyme q deficiency

SkeletalFeet:
pes cavus

NeurologicPeripheralNervousSystem:
areflexia
hyporeflexia
axonal sensory and motor peripheral neuropathy, severe
distal sensory loss
nerve biopsy shows axonal degeneration and axonal sprouting
more

Clinical features from OMIM:

208920

Human phenotypes related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

55 31 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 gait disturbance 55 31 hallmark (90%) Very frequent (99-80%) HP:0001288
3 peripheral neuropathy 55 31 hallmark (90%) Very frequent (99-80%) HP:0009830
4 medial flaring of the eyebrow 55 31 hallmark (90%) Very frequent (99-80%) HP:0010747
5 tremor 31 HP:0001337
6 muscle weakness 31 HP:0001324
7 dystonia 31 HP:0001332
8 gait ataxia 31 HP:0002066
9 dysarthria 31 HP:0001260
10 scoliosis 31 HP:0002650
11 cognitive impairment 31 HP:0100543
12 limb ataxia 31 HP:0002070
13 pes cavus 31 HP:0001761
14 progressive external ophthalmoplegia 31 HP:0000590
15 dementia 31 HP:0000726
16 abnormality of the nervous system 55 Very frequent (99-80%)
17 areflexia 31 HP:0001284
18 hypercholesterolemia 31 HP:0003124
19 hyporeflexia 31 HP:0001265
20 cerebellar atrophy 31 HP:0001272
21 choreoathetosis 31 very rare (1%) HP:0001266
22 oculomotor apraxia 31 HP:0000657
23 hypoalbuminemia 31 HP:0003073
24 distal sensory impairment 31 HP:0002936
25 distal amyotrophy 31 HP:0003693
26 truncal ataxia 31 HP:0002078
27 decreased number of large peripheral myelinated nerve fibers 31 HP:0003387
28 gaze-evoked nystagmus 31 HP:0000640
29 hypometric saccades 31 HP:0000571
30 peripheral axonal degeneration 31 HP:0000764

UMLS symptoms related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:


gait ataxia, ataxia, truncal, muscle weakness, tremor, cerebellar ataxia

GenomeRNAi Phenotypes related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 8.8 APTX HINT1 SETX

Drugs & Therapeutics for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Drugs for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ethanol Approved Phase 3 64-17-5 702
2
Coenzyme Q10 Approved, Investigational, Nutraceutical Phase 3 303-98-0 5281915
3 Complement System Proteins Phase 3
4 Micronutrients Phase 3
5 Trace Elements Phase 3
6 Ubiquinone Phase 3
7 Vitamins Phase 3
8 Lecithin Nutraceutical Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Evolution of Albumin on AOA1 Patients Supplemented With Coenzyme Q10 Completed NCT02333305 Phase 3

Search NIH Clinical Center for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Genetic Tests for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Genetic tests related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

# Genetic test Affiliating Genes
1 Adult Onset Ataxia with Oculomotor Apraxia 28 APTX

Anatomical Context for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

MalaCards organs/tissues related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

38
Eye, Testes

Publications for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Articles related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

(show all 14)
# Title Authors Year
1
Clinical, Biomarker, and Molecular Delineations and Genotype-Phenotype Correlations of Ataxia With Oculomotor Apraxia Type 1. ( 29356829 )
2018
2
Complete APTX deletion in a patient with ataxia with oculomotor apraxia type 1. ( 26285866 )
2015
3
Ataxia with Oculomotor Apraxia Type 1 without Oculomotor Apraxia: A Case Report. ( 26541496 )
2015
4
Progressive ataxia associated with ocular apraxia type 1 (AOA1) with a presence of a novel mutation on the aprataxin gene. ( 23956581 )
2013
5
A novel mutation in the aprataxin (APTX) gene in an Iranian individual suffering early-onset ataxia with oculomotor apraxia type 1(AOA1) disease. ( 23183622 )
2012
6
Structure of an aprataxin-DNA complex with insights into AOA1 neurodegenerative disease. ( 21984210 )
2011
7
Ataxia with oculomotor apraxia type1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients. ( 21465257 )
2011
8
Complete deletion of the aprataxin gene: ataxia with oculomotor apraxia type 1 with severe phenotype and cognitive deficit. ( 21686683 )
2009
9
Complete deletion of the aprataxin gene: ataxia with oculomotor apraxia type 1 with severe phenotype and cognitive deficit. ( 18202221 )
2008
10
Ataxia with oculomotor apraxia type 1 (AOA1): clinical and neuropsychological features in 2 new patients and differential diagnosis. ( 18403580 )
2008
11
Nigrostriatal involvement in ataxia with oculomotor apraxia type 1. ( 18004640 )
2008
12
Ataxia with oculomotor apraxia type 1 in Southern Italy: late onset and variable phenotype. ( 15596775 )
2004
13
Cerebellar ataxia with oculomotor apRAxia type 1: clinical and genetic studies. ( 14506070 )
2003
14
Ataxia with Oculomotor Apraxia Type 1 ( 20301629 )
1993

Variations for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

UniProtKB/Swiss-Prot genetic disease variations for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

71
# Symbol AA change Variation ID SNP ID
1 APTX p.Lys211Gln VAR_018794
2 APTX p.Ala212Val VAR_018795 rs748165574
3 APTX p.Arg213His VAR_018796 rs150886026
4 APTX p.His215Arg VAR_018797 rs121908133
5 APTX p.Pro220Leu VAR_018798 rs121908131
6 APTX p.Val277Gly VAR_018799 rs121908132
7 APTX p.Asp281Gly VAR_018800
8 APTX p.Trp293Arg VAR_018801 rs773393618
9 APTX p.Leu237Pro VAR_025365 rs267606665

ClinVar genetic disease variations for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

6 (show all 11)
# Gene Variation Type Significance SNP ID Assembly Location
1 APTX NM_175073.2(APTX): c.689dupT (p.Glu232Glyfs) duplication Pathogenic rs587776593 GRCh37 Chromosome 9, 32984710: 32984710
2 APTX NM_175073.2(APTX): c.617C> T (p.Pro206Leu) single nucleotide variant Pathogenic rs121908131 GRCh37 Chromosome 9, 32984782: 32984782
3 APTX NM_175073.2(APTX): c.840delT (p.Ser281Leufs) deletion Pathogenic rs587776594 GRCh37 Chromosome 9, 32974490: 32974490
4 APTX NM_175073.2(APTX): c.788T> G (p.Val263Gly) single nucleotide variant Pathogenic rs121908132 GRCh37 Chromosome 9, 32974542: 32974542
5 APTX NM_175073.2(APTX): c.602A> G (p.His201Arg) single nucleotide variant Pathogenic rs121908133 GRCh37 Chromosome 9, 32984797: 32984797
6 APTX APTX, IVS7AS, G-A, -1 single nucleotide variant Pathogenic
7 APTX NM_175073.2(APTX): c.837G> A (p.Trp279Ter) single nucleotide variant Pathogenic rs104894103 GRCh37 Chromosome 9, 32974493: 32974493
8 APTX NC_000009.12: g.(?_32973498)_(33001604_?)del deletion Pathogenic GRCh38 Chromosome 9, 32973498: 33001604
9 APTX NM_175073.2(APTX): c.668T> C (p.Leu223Pro) single nucleotide variant Pathogenic rs267606665 GRCh37 Chromosome 9, 32984731: 32984731
10 APTX NM_001195248.1(APTX): c.739A> T (p.Lys247Ter) single nucleotide variant Pathogenic rs1114167423 GRCh38 Chromosome 9, 32984704: 32984704
11 APTX NM_175073.2(APTX): c.875-2A> G single nucleotide variant Pathogenic rs904293109 GRCh37 Chromosome 9, 32973652: 32973652

Expression for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Search GEO for disease gene expression data for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia.

Pathways for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Pathways related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia according to KEGG:

36
# Name Kegg Source Accession
1 Base excision repair hsa03410
2 Nucleotide excision repair hsa03420
3 Homologous recombination hsa03440

GO Terms for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Cellular components related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.1 APTX CNOT3 HINT1 SACS SETX TTPA

Sources for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
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70 UMLS via Orphanet
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