MCID: SPS153
MIFTS: 39

Spastic Paraplegia 35, Autosomal Recessive

Categories: Genetic diseases, Rare diseases, Gastrointestinal diseases, Bone diseases, Mental diseases, Neuronal diseases, Eye diseases, Metabolic diseases

Aliases & Classifications for Spastic Paraplegia 35, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 35, Autosomal Recessive:

Name: Spastic Paraplegia 35, Autosomal Recessive 53 49 71 13
Fatty Acid Hydroxylase-Associated Neurodegeneration 53 12 23 49 24 55 71 69
Fahn 53 12 49 24 55 71
Spg35 53 12 49 55 71
Leukodystrophy, Dysmyelinating, and Spastic Paraparesis with or Without Dystonia 53 49 69
Autosomal Recessive Spastic Paraplegia Type 35 12 55
Hereditary Spastic Paraplegia 35 12 14
Spastic Paraplegia 35 24 28
Leukodystrophy, Dysmyelinating and Spastic Paraparesis with or Without Dystonia 12
Leukodystrophy Dysmyelinating and Spastic Paraparesis with or Without Dystonia 71
Fatty Acid Hydroxylase-Associated Neurodegeneration; Fahn 53
Dysmyelinating Leukodystrophy and Spastic Paraparesis 24
Autosomal Recessive Spastic Paraplegia 35 12

Characteristics:

Orphanet epidemiological data:

55
autosomal recessive spastic paraplegia type 35
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Childhood; Age of death: adolescent,adult;
fatty acid hydroxylase-associated neurodegeneration
Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Childhood;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset between 3 and 11 years of age
most patients become wheelchair-bound in adolescence or as young adults


HPO:

31
spastic paraplegia 35, autosomal recessive:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Spastic Paraplegia 35, Autosomal Recessive

UniProtKB/Swiss-Prot : 71 Spastic paraplegia 35, autosomal recessive: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG35 is a complicated form characterized by childhood onset of gait difficulties. It has a rapid progression and many patients become wheelchair-bound as young adults. Patients manifest cognitive decline associated with leukodystrophy. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur.

MalaCards based summary : Spastic Paraplegia 35, Autosomal Recessive, also known as fatty acid hydroxylase-associated neurodegeneration, is related to paraplegia and hereditary spastic paraplegia, and has symptoms including seizures, dystonia and nystagmus. An important gene associated with Spastic Paraplegia 35, Autosomal Recessive is FA2H (Fatty Acid 2-Hydroxylase). Affiliated tissues include brain, eye and globus pallidus.

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the FA2H gene on chromosome 16q23.1.

Genetics Home Reference : 24 Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a progressive disorder of the nervous system (neurodegeneration) characterized by problems with movement and vision that begin during childhood or adolescence.

NIH Rare Diseases : 49 This condition doesn't have a summary yet. Please see our page(s) on Neurodegeneration with brain iron accumulation.

OMIM : 53 Autosomal recessive spastic paraplegia-35 is a complicated form of SPG characterized by childhood onset of gait difficulties due to progressive spastic paraparesis, dysarthria, and mild cognitive decline associated with leukodystrophy on brain imaging. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur (summary by Dick et al., 2010). In addition, some patients with mutations in the FA2H gene have radiographic evidence of neurodegeneration with brain iron accumulation (NBIA), thus expanding the phenotype. Kruer et al. (2010) referred to this phenotypic spectrum of disorders as fatty acid hydrolase-associated neurodegeneration (FAHN). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). (612319)

GeneReviews: NBK56080

Related Diseases for Spastic Paraplegia 35, Autosomal Recessive

Diseases in the Spastic Paraplegia 3a family:

Spastic Paraplegia 3, Autosomal Dominant Spastic Paraplegia 4, Autosomal Dominant
Spastic Paraplegia 17, Autosomal Dominant Spastic Paraplegia 15, Autosomal Recessive
Spastic Paraplegia 23 Spastic Paraplegia 5a, Autosomal Recessive
Spastic Paraplegia 20, Autosomal Recessive Spastic Paraplegia 6, Autosomal Dominant
Spastic Paraplegia 9a, Autosomal Dominant Spastic Paraplegia 8, Autosomal Dominant
Spastic Paraplegia 10, Autosomal Dominant Spastic Paraplegia 11, Autosomal Recessive
Spastic Paraplegia 12, Autosomal Dominant Spastic Paraplegia 14, Autosomal Recessive
Spastic Paraplegia 13, Autosomal Dominant Spastic Paraplegia 19, Autosomal Dominant
Spastic Paraplegia 7, Autosomal Recessive Spastic Paraplegia 24, Autosomal Recessive
Spastic Paraplegia 25, Autosomal Recessive Spastic Paraplegia 27, Autosomal Recessive
Spastic Paraplegia 26, Autosomal Recessive Spastic Paraplegia 28, Autosomal Recessive
Spastic Paraplegia 29, Autosomal Dominant Spastic Paraplegia 33, Autosomal Dominant
Spastic Paraplegia 31, Autosomal Dominant Spastic Paraplegia 30, Autosomal Recessive
Spastic Paraplegia 18, Autosomal Recessive Spastic Paraplegia 32, Autosomal Recessive
Spastic Paraplegia 37, Autosomal Dominant Spastic Paraplegia 39, Autosomal Recessive
Spastic Paraplegia 35, Autosomal Recessive Spastic Paraplegia 38, Autosomal Dominant
Spastic Paraplegia 42, Autosomal Dominant Spastic Paraplegia 50, Autosomal Recessive
Spastic Paraplegia 36, Autosomal Dominant Spastic Paraplegia 45, Autosomal Recessive
Spastic Paraplegia 44, Autosomal Recessive Spastic Paraplegia 41, Autosomal Dominant
Spastic Paraplegia 48, Autosomal Recessive Spastic Paraplegia 51, Autosomal Recessive
Spastic Paraplegia 47, Autosomal Recessive Spastic Paraplegia 52, Autosomal Recessive
Spastic Paraplegia 46, Autosomal Recessive Spastic Paraplegia 53, Autosomal Recessive
Spastic Paraplegia 56, Autosomal Recessive Spastic Paraplegia 49, Autosomal Recessive
Spastic Paraplegia 54, Autosomal Recessive Spastic Paraplegia 55, Autosomal Recessive
Spastic Paraplegia 43, Autosomal Recessive Spastic Paraplegia 79, Autosomal Recessive
Spastic Paraplegia 72, Autosomal Recessive Spastic Paraplegia 57, Autosomal Recessive
Spastic Paraplegia 62, Autosomal Recessive Spastic Paraplegia 64, Autosomal Recessive
Spastic Paraplegia 61, Autosomal Recessive Spastic Paraplegia 63, Autosomal Recessive
Spastic Paraplegia 73, Autosomal Dominant Spastic Paraplegia 74, Autosomal Recessive
Spastic Paraplegia 9b, Autosomal Recessive Spastic Paraplegia 75, Autosomal Recessive
Spastic Paraplegia 76, Autosomal Recessive Spastic Paraplegia 77, Autosomal Recessive
Spastic Paraplegia 78, Autosomal Recessive Hereditary Spastic Paraplegia
Hereditary Spastic Paraplegia 51 Hereditary Spastic Paraplegia 72
Spastic Paraplegia 4 Spastic Paraplegia 8
Spastic Paraplegia 11 Spastic Paraplegia 1
Spastic Paraplegia 10 Spastic Paraplegia 12
Spastic Paraplegia 13 Spastic Paraplegia 14
Spastic Paraplegia 15 Spastic Paraplegia 16
Spastic Paraplegia 17 Spastic Paraplegia 18
Spastic Paraplegia 19 Spastic Paraplegia 24
Spastic Paraplegia 25 Spastic Paraplegia 26
Spastic Paraplegia 29 Spastic Paraplegia 3
Spastic Paraplegia 31 Spastic Paraplegia 32
Spastic Paraplegia 39 Spastic Paraplegia 51
Spastic Paraplegia 5a Spastic Paraplegia 5b
Spastic Paraplegia 6 Spastic Paraplegia 9
Autosomal Recessive Spastic Paraplegia Type 60 Autosomal Recessive Spastic Paraplegia Type 59
Autosomal Recessive Spastic Paraplegia Type 68 Autosomal Recessive Spastic Paraplegia Type 69
Autosomal Recessive Spastic Paraplegia Type 70 Autosomal Recessive Spastic Paraplegia Type 71
Autosomal Recessive Spastic Paraplegia Type 66 Autosomal Recessive Spastic Paraplegia Type 67

Diseases related to Spastic Paraplegia 35, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 37)
# Related Disease Score Top Affiliating Genes
1 paraplegia 28.1 CYP2U1 DDHD2 FA2H SPG11 SPG21 ZFYVE26
2 hereditary spastic paraplegia 26.9 AP5Z1 CYP2U1 DDHD2 ERLIN2 FA2H SPG11
3 spastic paraplegia 28, autosomal recessive 10.2 AP5Z1 DDHD2
4 spasticity 10.2
5 neuropathy, hereditary sensory, with spastic paraplegia, autosomal recessive 10.2 SPG11 ZFYVE26
6 amyotrophic lateral sclerosis type 5 10.1 SPG11 SPG21
7 mast syndrome 10.1 SPG11 SPG21
8 spastic paraplegia 47, autosomal recessive 10.1 AP5Z1 ERLIN2
9 spastic paraplegia 32, autosomal recessive 10.1 SPG11 SPG21
10 spastic paraplegia 42, autosomal dominant 10.1 AP5Z1 ERLIN2
11 spastic paraplegia 13, autosomal dominant 10.1 AP5Z1 ERLIN2
12 spastic paraplegia 10, autosomal dominant 10.0 AP5Z1 SPG11
13 spastic paraplegia 49, autosomal recessive 10.0 SPG11 ZFYVE26
14 spastic paraparesis 10.0 FA2H SPG11
15 spastic paraplegia 2, x-linked 10.0 AP5Z1 ERLIN2
16 spastic paraplegia 6, autosomal dominant 10.0 AP5Z1 ERLIN2
17 spastic paraplegia 12, autosomal dominant 10.0 AP5Z1 ERLIN2
18 amyotrophic lateral sclerosis 1 9.9
19 parkinson disease, late-onset 9.9
20 lateral sclerosis 9.9
21 spastic paraplegia 11, autosomal recessive 9.9 SPG11 SPG21
22 spastic paraplegia 7, autosomal recessive 9.9 SPG11 ZFYVE26
23 spastic paraplegia 46, autosomal recessive 9.9 CYP2U1 SPG21
24 charcot-marie-tooth disease, axonal, type 2t 9.8 CYP2U1 SPG21
25 spastic paraplegia 39, autosomal recessive 9.8 AP5Z1 ERLIN2 ZFYVE26
26 spastic paraplegia 20, autosomal recessive 9.8 SPG11 ZFYVE26
27 spastic paraplegia 18, autosomal recessive 9.8 AP5Z1 ERLIN2 SPG21
28 spastic paraplegia 44, autosomal recessive 9.8 AP5Z1 ERLIN2 SPG21
29 spastic paraplegia 56, autosomal recessive 9.8 CYP2U1 DDHD2
30 spastic paraplegia 30, autosomal recessive 9.8 AP5Z1 ERLIN2 SPG21
31 spastic paraplegia 8, autosomal dominant 9.7 AP5Z1 ERLIN2 SPG11
32 masa syndrome 9.7 AP5Z1 ERLIN2 SPG11
33 axonal neuropathy 9.7 SPG11 ZFYVE26
34 spastic paraplegia 54, autosomal recessive 9.6 AP5Z1 CYP2U1 DDHD2
35 charcot-marie-tooth disease, axonal, type 2e 9.0 CYP2U1 FA2H SPG11 SPG21 ZFYVE26
36 spastic paraplegia 48, autosomal recessive 8.7 AP5Z1 DDHD2 ERLIN2 SPG11 SPG21 ZFYVE26
37 spastic paraplegia 15, autosomal recessive 8.3 AP5Z1 CYP2U1 DDHD2 FA2H SPG11 SPG21

Graphical network of the top 20 diseases related to Spastic Paraplegia 35, Autosomal Recessive:



Diseases related to Spastic Paraplegia 35, Autosomal Recessive

Symptoms & Phenotypes for Spastic Paraplegia 35, Autosomal Recessive

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
ataxia
seizures
dystonia
dysarthria
hyperreflexia
more
Genitourinary Bladder:
urinary urgency
incontinence (variable)

Head And Neck Eyes:
nystagmus
optic atrophy
strabismus
external ophthalmoplegia (less common)


Clinical features from OMIM:

612319

Human phenotypes related to Spastic Paraplegia 35, Autosomal Recessive:

31 (show all 25)
# Description HPO Frequency HPO Source Accession
1 seizures 31 HP:0001250
2 dystonia 31 HP:0001332
3 nystagmus 31 HP:0000639
4 intellectual disability 31 HP:0001249
5 dysarthria 31 HP:0001260
6 optic atrophy 31 HP:0000648
7 strabismus 31 HP:0000486
8 babinski sign 31 HP:0003487
9 dysmetria 31 HP:0001310
10 neurodegeneration 31 HP:0002180
11 difficulty walking 31 HP:0002355
12 mental deterioration 31 HP:0001268
13 spastic paraplegia 31 HP:0001258
14 cerebellar atrophy 31 HP:0001272
15 hypoplasia of the corpus callosum 31 HP:0002079
16 external ophthalmoplegia 31 occasional (7.5%) HP:0000544
17 spastic tetraparesis 31 HP:0001285
18 abnormality of the periventricular white matter 31 HP:0002518
19 urinary incontinence 31 occasional (7.5%) HP:0000020
20 spastic paraparesis 31 HP:0002313
21 lower limb spasticity 31 HP:0002061
22 atrophy/degeneration affecting the brainstem 31 HP:0007366
23 urinary urgency 31 HP:0000012
24 ankle clonus 31 occasional (7.5%) HP:0011448
25 dysmyelinating leukodystrophy 31 HP:0006978

UMLS symptoms related to Spastic Paraplegia 35, Autosomal Recessive:


ataxia, seizures, urgency of micturition

Drugs & Therapeutics for Spastic Paraplegia 35, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 35, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 35, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 35, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 35 28 FA2H

Anatomical Context for Spastic Paraplegia 35, Autosomal Recessive

MalaCards organs/tissues related to Spastic Paraplegia 35, Autosomal Recessive:

38
Brain, Eye, Globus Pallidus

Publications for Spastic Paraplegia 35, Autosomal Recessive

Articles related to Spastic Paraplegia 35, Autosomal Recessive:

# Title Authors Year
1
Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration. ( 22146942 )
2012
2
Fatty Acid Hydroxylase-Associated Neurodegeneration ( 21735565 )
1993

Variations for Spastic Paraplegia 35, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 35, Autosomal Recessive:

71
# Symbol AA change Variation ID SNP ID
1 FA2H p.Asp35Tyr VAR_054893 rs121918217
2 FA2H p.Arg235Cys VAR_064621 rs387907039
3 FA2H p.Arg154Cys VAR_065245 rs387907040

ClinVar genetic disease variations for Spastic Paraplegia 35, Autosomal Recessive:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 FA2H NM_024306.4(FA2H): c.703C> T (p.Arg235Cys) single nucleotide variant Pathogenic rs387907039 GRCh37 Chromosome 16, 74752969: 74752969
2 FA2H NM_024306.4(FA2H): c.159_176del18 (p.Arg53_Ile58del) deletion Pathogenic rs759947457 GRCh37 Chromosome 16, 74808478: 74808495
3 FA2H NM_024306.4(FA2H): c.460C> T (p.Arg154Cys) single nucleotide variant Pathogenic rs387907040 GRCh37 Chromosome 16, 74761188: 74761188
4 FA2H NM_024306.4(FA2H): c.510_511delCA (p.Tyr170Terfs) deletion Pathogenic rs587776891 GRCh38 Chromosome 16, 74726327: 74726328
5 FA2H NM_024306.4(FA2H): c.707T> C (p.Phe236Ser) single nucleotide variant Pathogenic rs387907172 GRCh37 Chromosome 16, 74752965: 74752965
6 FA2H NG_017070.1: g.(39810_52446)_(66877_?)del deletion Pathogenic GRCh38 Chromosome 16, 74712955: 74740022
7 FA2H FA2H, IVS5DS, G-A, +1 single nucleotide variant Pathogenic
8 FA2H NM_024306.4(FA2H): c.103G> T (p.Asp35Tyr) single nucleotide variant Pathogenic rs121918217 GRCh37 Chromosome 16, 74808551: 74808551
9 FA2H NM_024306.4(FA2H): c.517C> T (p.Pro173Ser) single nucleotide variant Likely pathogenic rs863224870 GRCh38 Chromosome 16, 74726321: 74726321

Expression for Spastic Paraplegia 35, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 35, Autosomal Recessive.

Pathways for Spastic Paraplegia 35, Autosomal Recessive

GO Terms for Spastic Paraplegia 35, Autosomal Recessive

Cellular components related to Spastic Paraplegia 35, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 organelle membrane GO:0031090 8.62 CYP2U1 FA2H

Biological processes related to Spastic Paraplegia 35, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.13 DDHD2 ERLIN2 FA2H
2 double-strand break repair via homologous recombination GO:0000724 8.62 AP5Z1 ZFYVE26

Sources for Spastic Paraplegia 35, Autosomal Recessive

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
69 UMLS
70 UMLS via Orphanet
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