MCID: SPS153
MIFTS: 37

Spastic Paraplegia 35, Autosomal Recessive

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

Aliases & Classifications for Spastic Paraplegia 35, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 35, Autosomal Recessive:

Name: Spastic Paraplegia 35, Autosomal Recessive 54 50 71 13
Fatty Acid Hydroxylase-Associated Neurodegeneration 12 23 50 24 25 56 71 69
Fahn 12 50 25 56 71
Spg35 12 50 56 71
Leukodystrophy, Dysmyelinating, and Spastic Paraparesis with or Without Dystonia 50 69
Autosomal Recessive Spastic Paraplegia Type 35 12 56
Hereditary Spastic Paraplegia 35 12 14
Leukodystrophy, Dysmyelinating and Spastic Paraparesis with or Without Dystonia 12
Dysmyelinating Leukodystrophy and Spastic Paraparesis with or Without Dystonia 24
Leukodystrophy Dysmyelinating and Spastic Paraparesis with or Without Dystonia 71
Dysmyelinating Leukodystrophy and Spastic Paraparesis 25
Autosomal Recessive Spastic Paraplegia 35 12
Spastic Paraplegia 35 25

Characteristics:

Orphanet epidemiological data:

56
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:

54
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:

32
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 spastic paraplegia 35 and l-2-hydroxyglutaric aciduria, and has symptoms including optic atrophy, nystagmus and dystonia. 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 : 25 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 : 50 this condition doesn't have a summary yet. please see our page(s) on neurodegeneration with brain iron accumulation.

OMIM : 54
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 78, Autosomal Recessive Spastic Paraplegia 29, Autosomal Dominant
Spastic Paraplegia 63 Spastic Paraplegia 47, Autosomal Recessive
Spastic Paraplegia 23 Spastic Paraplegia 44, Autosomal Recessive
Spastic Paraplegia 74, Autosomal Recessive Spastic Paraplegia 4, Autosomal Dominant
Spastic Paraplegia 31, Autosomal Dominant Spastic Paraplegia 13, Autosomal Dominant
Spastic Paraplegia 30, Autosomal Recessive Spastic Paraplegia 57, Autosomal Recessive
Spastic Paraplegia 42, Autosomal Dominant Spastic Paraplegia 14, Autosomal Recessive
Spastic Paraplegia 38, Autosomal Dominant Spastic Paraplegia 79, Autosomal Recessive
Spastic Paraplegia 56, Autosomal Recessive Spastic Paraplegia 72, Autosomal Recessive
Spastic Paraplegia 77, Autosomal Recessive Spastic Paraplegia 25, Autosomal Recessive
Spastic Paraplegia 48, Autosomal Recessive Spastic Paraplegia 50, Autosomal Recessive
Spastic Paraplegia 53, Autosomal Recessive Spastic Paraplegia 37, Autosomal Dominant
Spastic Paraplegia 54, Autosomal Recessive Spastic Paraplegia 18, Autosomal Recessive
Spastic Paraplegia 5a, Autosomal Recessive Spastic Paraplegia 8, Autosomal Dominant
Spastic Paraplegia 46, Autosomal Recessive Spastic Paraplegia 19, Autosomal Dominant
Spastic Paraplegia 27, Autosomal Recessive Spastic Paraplegia 64, Autosomal Recessive
Spastic Paraplegia 33, Autosomal Dominant Spastic Paraplegia 9a, Autosomal Dominant
Spastic Paraplegia 9b, Autosomal Recessive Spastic Paraplegia 45, Autosomal Recessive
Spastic Paraplegia 62 Spastic Paraplegia 41, Autosomal Dominant
Spastic Paraplegia 76, Autosomal Recessive Spastic Paraplegia 10, Autosomal Dominant
Spastic Paraplegia 26, Autosomal Recessive Spastic Paraplegia 36, Autosomal Dominant
Spastic Paraplegia 55, Autosomal Recessive Spastic Paraplegia 24, Autosomal Recessive
Spastic Paraplegia 3a, Autosomal Dominant Spastic Paraplegia 52, Autosomal Recessive
Spastic Paraplegia 32, Autosomal Recessive Spastic Paraplegia 28, Autosomal Recessive
Spastic Paraplegia 15, Autosomal Recessive Spastic Paraplegia 49, Autosomal Recessive
Spastic Paraplegia 6, Autosomal Dominant Spastic Paraplegia 11, Autosomal Recessive
Spastic Paraplegia 51, Autosomal Recessive Spastic Paraplegia 61, Autosomal Recessive
Spastic Paraplegia 35, Autosomal Recessive Spastic Paraplegia 7, Autosomal Recessive
Spastic Paraplegia 39, Autosomal Recessive Spastic Paraplegia 43, Autosomal Recessive
Spastic Paraplegia 75, Autosomal Recessive Spastic Paraplegia 12, Autosomal Dominant
Spastic Paraplegia 73, Autosomal Dominant Hereditary Spastic Paraplegia
Hereditary Spastic Paraplegia 3a Hereditary Spastic Paraplegia 51
Hereditary Spastic Paraplegia 62 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
Spastic Paraplegia 28 Spastic Paraplegia 30
Spastic Paraplegia 33 Spastic Paraplegia 35
Spastic Paraplegia 42 Spastic Paraplegia 43
Spastic Paraplegia 45 Spastic Paraplegia 46
Spastic Paraplegia 47 Spastic Paraplegia 48
Spastic Paraplegia 49 Spastic Paraplegia 50
Spastic Paraplegia 52 Spastic Paraplegia 53
Spastic Paraplegia 54 Spastic Paraplegia 55
Spastic Paraplegia 56 Spastic Paraplegia 57
Spastic Paraplegia 59 Spastic Paraplegia 61
Spastic Paraplegia 64 Spastic Paraplegia 66
Spastic Paraplegia 72 Spastic Paraplegia 75
Spastic Paraplegia 76 Spastic Paraplegia 44
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 34)
id Related Disease Score Top Affiliating Genes
1 spastic paraplegia 35 11.1
2 l-2-hydroxyglutaric aciduria 10.3 AP5Z1 DDHD2
3 chromosome 15q11.2 deletion syndrome 10.3 AP5Z1 ERLIN2
4 amyotrophic lateral sclerosis type 14 10.2 SPG11 SPG21
5 spastic paraplegia 47, autosomal recessive 10.2 AP5Z1 ERLIN2
6 immunodeficiency 43 10.2 SPG11 SPG21
7 congenital cataracts, hearing loss, and neurodegeneration 10.1 AP5Z1 ERLIN2
8 rett syndrome, congenital variant 10.1 SPG11 SPG21
9 herpes simplex encephalitis 3 10.1 SPG11 ZFYVE26
10 leukodystrophy, hypomyelinating, 4 10.1 AP5Z1 ERLIN2
11 myoclonus, intractable, neonatal 10.0 AP5Z1 SPG11
12 ichthyosis, congenital, autosomal recessive 14 10.0 AP5Z1 ERLIN2
13 spastic paraplegia 13 10.0 FA2H SPG11
14 phosphoribosylpyrophosphate synthetase superactivity 10.0 AP5Z1 ERLIN2
15 pseudosarcomatous fibromatosis 9.9 SPG11 ZFYVE26
16 spastic paraplegia 4, autosomal dominant 9.9 AP5Z1 SPG11
17 spinocerebellar ataxia 43 9.9 CYP2U1 SPG21
18 lateral sclerosis 9.9
19 sialuria 9.8 CYP2U1 SPG21
20 boucher-neuhauser syndrome 9.8 AP5Z1 ERLIN2 ZFYVE26
21 spastic paraplegia 44, autosomal recessive 9.8 AP5Z1 ERLIN2 SPG21
22 immunodeficiency 15 9.8 AP5Z1 ERLIN2 SPG21
23 neuropathy, hereditary sensory, type iic 9.8 AP5Z1 ERLIN2 SPG21
24 hypomagnesemia 4, renal 9.7 CYP2U1 DDHD2
25 ritscher-schinzel syndrome 1 9.7 AP5Z1 ERLIN2 SPG11
26 major affective disorder 2 9.7 AP5Z1 ERLIN2 SPG11
27 amyotrophic lateral sclerosis 5, juvenile 9.6 SPG11 SPG21
28 pituitary adenoma, growth hormone-secreting 9.5 CYP2U1 SPG21 ZFYVE26
29 basal ganglia calcification, idiopathic, 1 9.5 AP5Z1 CYP2U1 DDHD2
30 b-cell expansion with nfkb and t-cell anergy 8.3 AP5Z1 DDHD2 ERLIN2 SPG11 SPG21 ZFYVE26
31 human venous malformation 8.1 CYP2U1 DDHD2 FA2H SPG11 SPG21 ZFYVE26
32 pediatric ovarian germ cell tumor 8.1 CYP2U1 DDHD2 FA2H SPG11 SPG21 ZFYVE26
33 methylmalonic aciduria and homocystinuria, cblj type 7.8 AP5Z1 CYP2U1 DDHD2 FA2H SPG11 SPG21
34 hirschsprung disease 8 7.1 AP5Z1 CYP2U1 DDHD2 ERLIN2 FA2H SPG11

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:

54

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

Genitourinary- Bladder:
urinary urgency
incontinence (variable)

Neurologic- Central Nervous System:
dystonia
dysarthria
ataxia
spastic quadriparesis
hyperreflexia
more

Clinical features from OMIM:

612319

Human phenotypes related to Spastic Paraplegia 35, Autosomal Recessive:

32 (show all 24)
id Description HPO Frequency HPO Source Accession
1 optic atrophy 32 HP:0000648
2 nystagmus 32 HP:0000639
3 dystonia 32 HP:0001332
4 dysarthria 32 HP:0001260
5 strabismus 32 HP:0000486
6 spastic paraplegia 32 HP:0001258
7 seizures 32 HP:0001250
8 intellectual disability 32 HP:0001249
9 hypoplasia of the corpus callosum 32 HP:0002079
10 urinary urgency 32 HP:0000012
11 lower limb spasticity 32 HP:0002061
12 cerebellar atrophy 32 HP:0001272
13 urinary incontinence 32 occasional (7.5%) HP:0000020
14 spastic paraparesis 32 HP:0002313
15 dysmetria 32 HP:0001310
16 neurodegeneration 32 HP:0002180
17 ankle clonus 32 occasional (7.5%) HP:0011448
18 difficulty walking 32 HP:0002355
19 mental deterioration 32 HP:0001268
20 spastic tetraparesis 32 HP:0001285
21 external ophthalmoplegia 32 occasional (7.5%) HP:0000544
22 babinski sign 32 HP:0003487
23 abnormality of the periventricular white matter 32 HP:0002518
24 dysmyelinating leukodystrophy 32 HP:0006978

UMLS symptoms related to Spastic Paraplegia 35, Autosomal Recessive:


ataxia, seizures

Drugs & Therapeutics for Spastic Paraplegia 35, Autosomal Recessive

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search 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:

id Genetic test Affiliating Genes
1 Fatty Acid Hydroxylase-Associated Neurodegeneration 24 FA2H
2 Dysmyelinating Leukodystrophy and Spastic Paraparesis with or Without Dystonia 24

Anatomical Context for Spastic Paraplegia 35, Autosomal Recessive

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

39
Brain, Eye, Globus Pallidus

Publications for Spastic Paraplegia 35, Autosomal Recessive

Variations for Spastic Paraplegia 35, Autosomal Recessive

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

71
id 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
id Gene Variation Type Significance SNP ID Assembly Location
1 FA2H FA2H, IVS5DS, G-A, +1 single nucleotide variant Pathogenic
2 FA2H NM_024306.4(FA2H): c.103G> T (p.Asp35Tyr) single nucleotide variant Pathogenic rs121918217 GRCh37 Chromosome 16, 74808551: 74808551
3 FA2H NM_024306.4(FA2H): c.703C> T (p.Arg235Cys) single nucleotide variant Pathogenic rs387907039 GRCh37 Chromosome 16, 74752969: 74752969
4 FA2H NM_024306.4(FA2H): c.159_176del18 (p.Arg53_Ile58del) deletion Pathogenic rs759947457 GRCh37 Chromosome 16, 74808478: 74808495
5 FA2H NM_024306.4(FA2H): c.460C> T (p.Arg154Cys) single nucleotide variant Pathogenic rs387907040 GRCh37 Chromosome 16, 74761188: 74761188
6 FA2H NM_024306.4(FA2H): c.510_511delCA (p.Tyr170Terfs) deletion Pathogenic rs587776891 GRCh38 Chromosome 16, 74726327: 74726328
7 FA2H NM_024306.4(FA2H): c.707T> C (p.Phe236Ser) single nucleotide variant Pathogenic rs387907172 GRCh37 Chromosome 16, 74752965: 74752965
8 FA2H NG_017070.1: g.(39810_52446)_(66877_?)del deletion Pathogenic GRCh38 Chromosome 16, 74712955: 74740022
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:

id 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:

id 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
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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