SPG9B
MCID: SPS159
MIFTS: 40

Spastic Paraplegia 9b, Autosomal Recessive (SPG9B)

Categories: Bone diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Spastic Paraplegia 9b, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 9b, Autosomal Recessive:

Name: Spastic Paraplegia 9b, Autosomal Recessive 57 72 29 6
Spg9b 57 12 72
Hereditary Spastic Paraplegia 9b 12 15
Autosomal Recessive Complex Spastic Paraplegia Type 9b 12
Autosomal Recessive Spastic Paraplegia Type 9b 58
Autosomal Recessive Spastic Paraplegia 9b 12
Ar-Spg9b 58

Characteristics:

Orphanet epidemiological data:

58
autosomal recessive spastic paraplegia type 9b
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
two unrelated families have been reported (last curated october 2015)
onset in first decade (range 1 to 7 years)
no skin abnormalities


HPO:

31
spastic paraplegia 9b, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Spastic Paraplegia 9b, Autosomal Recessive

UniProtKB/Swiss-Prot : 72 Spastic paraplegia 9B, 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. SPG9B is a complex form characterized by delayed psychomotor development, intellectual disability, and severe motor impairment. Dysmorphic facial features, tremor, and urinary incontinence are variably observed in SPG9B patients.

MalaCards based summary : Spastic Paraplegia 9b, Autosomal Recessive, also known as spg9b, is related to autosomal dominant spastic paraplegia type 9b and autosomal recessive cutis laxa type i. An important gene associated with Spastic Paraplegia 9b, Autosomal Recessive is ALDH18A1 (Aldehyde Dehydrogenase 18 Family Member A1), and among its related pathways/superpathways are Carbon metabolism and Amino Acid metabolism. Affiliated tissues include skin and skeletal muscle, and related phenotypes are babinski sign and lower limb hyperreflexia

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in autosomal recessive homozygous or compound heterozygous mutation in the ALDH18A1 gene on chromosome 10q24.

OMIM® : 57 Autosomal recessive SPG9B is a neurologic disorder characterized by early-onset complex spastic paraplegia. Affected individuals had delayed psychomotor development, intellectual disability, and severe motor impairment. More variable features include dysmorphic facial features, tremor, and urinary incontinence (summary by Coutelier et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800). (616586) (Updated 05-Apr-2021)

Related Diseases for Spastic Paraplegia 9b, 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, Autosomal Recessive 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 Dominant
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 Spastic Paraplegia 80, Autosomal Dominant
Spastic Paraplegia 81, Autosomal Recessive Spastic Paraplegia 82, Autosomal Recessive
Spastic Paraplegia 83, Autosomal Recessive Hereditary Spastic Paraplegia 23
Hereditary Spastic Paraplegia 30 Hereditary Spastic Paraplegia 51
Hereditary Spastic Paraplegia 72 Hereditary Spastic Paraplegia
Spastic Paraplegia 4 Spastic Paraplegia 8
Spastic Paraplegia 11 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 32
Spastic Paraplegia 39 Spastic Paraplegia 47
Spastic Paraplegia 5a Spastic Paraplegia 5b
Spastic Paraplegia 6 Spastic Paraplegia 9
Spastic Paraplegia Type 49 Autosomal Recessive Spastic Paraplegia Type 60
Autosomal Recessive Spastic Paraplegia Type 59 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
Autosomal Dominant Spastic Paraplegia Type 9b

Diseases related to Spastic Paraplegia 9b, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 19)
# Related Disease Score Top Affiliating Genes
1 autosomal dominant spastic paraplegia type 9b 11.0
2 autosomal recessive cutis laxa type i 10.0 PYCR1 ALDH18A1
3 cutis laxa 10.0 PYCR1 ALDH18A1
4 cutis laxa, autosomal recessive, type iiib 9.9 PYCR1 ALDH18A1
5 cutis laxa, autosomal recessive, type iia 9.9 PYCR1 ALDH18A1
6 cutis laxa, autosomal recessive, type iiia 9.9 PYCR1 ALDH18A1
7 cutis laxa, autosomal recessive, type ic 9.9 PYCR1 ALDH18A1
8 cutis laxa, autosomal recessive, type ib 9.9 PYCR1 ALDH18A1
9 borderline glaucoma 9.9 PYCR3 PYCR1
10 cutis laxa, autosomal recessive, type ia 9.9 PYCR1 ALDH18A1
11 hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 9.9 OTC ALDH18A1
12 autosomal recessive cutis laxa type ii classic type 9.8 PYCR1 ALDH18A1
13 geroderma osteodysplasticum 9.7 PYCR1 ALDH18A1
14 argininemia 9.7 OTC ALDH18A1
15 autosomal recessive cutis laxa type iii 9.7 PYCR3 PYCR1 ALDH18A1
16 cutis laxa, autosomal recessive, type iib 9.7 PYCR3 PYCR1 ALDH18A1
17 leukodystrophy, hypomyelinating, 10 9.7 PYCR3 PYCR1 ALDH18A1
18 hyperprolinemia 9.7 PYCR3 PYCR1 ALDH18A1
19 spastic paraplegia 9a, autosomal dominant 8.7 PYCR3 PYCR1 PPP2R3C OTC GDAP1 ALDH18A1

Graphical network of the top 20 diseases related to Spastic Paraplegia 9b, Autosomal Recessive:



Diseases related to Spastic Paraplegia 9b, Autosomal Recessive

Symptoms & Phenotypes for Spastic Paraplegia 9b, Autosomal Recessive

Human phenotypes related to Spastic Paraplegia 9b, Autosomal Recessive:

58 31 (show all 38)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0003487
2 lower limb hyperreflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002395
3 hyperreflexia in upper limbs 58 31 hallmark (90%) Very frequent (99-80%) HP:0007350
4 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
5 tetraplegia 58 31 occasional (7.5%) Frequent (79-30%) HP:0002445
6 muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0001324
7 motor delay 58 31 frequent (33%) Frequent (79-30%) HP:0001270
8 spastic gait 58 31 frequent (33%) Frequent (79-30%) HP:0002064
9 postural tremor 58 31 frequent (33%) Frequent (79-30%) HP:0002174
10 impaired continence 58 31 frequent (33%) Frequent (79-30%) HP:0031064
11 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001263
12 delayed speech and language development 58 31 occasional (7.5%) Occasional (29-5%) HP:0000750
13 abnormal facial shape 58 31 occasional (7.5%) Occasional (29-5%) HP:0001999
14 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
15 short stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0004322
16 skeletal muscle atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003202
17 toe walking 58 31 occasional (7.5%) Occasional (29-5%) HP:0040083
18 kyphoscoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002751
19 cerebral cortical atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002120
20 abnormality of the periventricular white matter 58 31 occasional (7.5%) Occasional (29-5%) HP:0002518
21 urinary retention 58 31 occasional (7.5%) Occasional (29-5%) HP:0000016
22 loss of speech 58 31 occasional (7.5%) Occasional (29-5%) HP:0002371
23 pollakisuria 58 31 occasional (7.5%) Occasional (29-5%) HP:0100515
24 corpus callosum atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0007371
25 absent achilles reflex 58 31 occasional (7.5%) Occasional (29-5%) HP:0003438
26 primitive reflex 58 31 occasional (7.5%) Occasional (29-5%) HP:0002476
27 impaired vibration sensation at ankles 58 31 occasional (7.5%) Occasional (29-5%) HP:0006938
28 tremor 31 occasional (7.5%) HP:0001337
29 cataract 31 occasional (7.5%) HP:0000518
30 foot dorsiflexor weakness 31 occasional (7.5%) HP:0009027
31 pseudobulbar paralysis 31 occasional (7.5%) HP:0007024
32 spasticity 58 31 Very frequent (99-80%) HP:0001257
33 intellectual disability 31 HP:0001249
34 hyperreflexia 31 HP:0001347
35 gait disturbance 31 HP:0001288
36 absent speech 31 HP:0001344
37 growth delay 58 Frequent (79-30%)
38 spastic paraplegia 31 HP:0001258

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
intellectual disability
spasticity
hyperreflexia
dysarthria
extensor plantar responses
more
Growth Height:
short stature

Growth Other:
growth retardation

Head And Neck Face:
dysmorphic facial features

Neurologic Peripheral Nervous System:
distal vibration sense (in some patients)

Head And Neck Head:
microcephaly

Genitourinary Bladder:
urinary retention
urinary incontinence

Muscle Soft Tissue:
muscle atrophy

Head And Neck Eyes:
cataract (1 patient)

Clinical features from OMIM®:

616586 (Updated 05-Apr-2021)

Drugs & Therapeutics for Spastic Paraplegia 9b, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 9b, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 9b, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 9b, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 9b, Autosomal Recessive 29 ALDH18A1

Anatomical Context for Spastic Paraplegia 9b, Autosomal Recessive

MalaCards organs/tissues related to Spastic Paraplegia 9b, Autosomal Recessive:

40
Skin, Skeletal Muscle

Publications for Spastic Paraplegia 9b, Autosomal Recessive

Articles related to Spastic Paraplegia 9b, Autosomal Recessive:

# Title Authors PMID Year
1
Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia. 6 57
26026163 2015
2
ALDH18A1 gene mutations cause dominant spastic paraplegia SPG9: loss of function effect and plausibility of a dominant negative mechanism. 6
26297558 2016
3
SPG9A with the new occurrence of an ALDH18A1 mutation in a CMT1A family with PMP22 duplication: case report. 61
33573605 2021
4
Tremor as an early sign of hereditary spastic paraplegia due to mutations in ALDH18A1. 61
32798076 2021
5
Δ1 -Pyrroline-5-carboxylate synthetase deficiency: An emergent multifaceted urea cycle-related disorder. 61
32017139 2020
6
P5CS expression study in a new family with ALDH18A1-associated hereditary spastic paraplegia SPG9. 61
31402623 2019
7
Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment. 61
29915212 2018

Variations for Spastic Paraplegia 9b, Autosomal Recessive

ClinVar genetic disease variations for Spastic Paraplegia 9b, Autosomal Recessive:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ALDH18A1 NM_002860.4(ALDH18A1):c.1910T>C (p.Leu637Pro) SNV Pathogenic 217120 rs869320690 GRCh37: 10:97373512-97373512
GRCh38: 10:95613755-95613755
2 ALDH18A1 NM_002860.4(ALDH18A1):c.2143G>C (p.Asp715His) SNV Pathogenic 217115 rs752669339 GRCh37: 10:97370017-97370017
GRCh38: 10:95610260-95610260
3 ALDH18A1 NM_002860.4(ALDH18A1):c.383G>A (p.Arg128His) SNV Pathogenic 217121 rs768323248 GRCh37: 10:97397114-97397114
GRCh38: 10:95637357-95637357
4 ALDH18A1 NM_002860.4(ALDH18A1):c.1867G>A (p.Asp623Asn) SNV Uncertain significance 424961 rs770815414 GRCh37: 10:97373555-97373555
GRCh38: 10:95613798-95613798
5 ALDH18A1 NM_002860.4(ALDH18A1):c.1078+6T>C SNV Uncertain significance 1029647 GRCh37: 10:97387193-97387193
GRCh38: 10:95627436-95627436
6 ALDH18A1 NM_002860.4(ALDH18A1):c.1942C>T (p.Pro648Ser) SNV not provided 441102 rs768964431 GRCh37: 10:97371181-97371181
GRCh38: 10:95611424-95611424

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 9b, Autosomal Recessive:

72
# Symbol AA change Variation ID SNP ID
1 ALDH18A1 p.Arg128His VAR_075886 rs768323248
2 ALDH18A1 p.Leu637Pro VAR_075892 rs869320690
3 ALDH18A1 p.Asp715His VAR_075895 rs752669339

Expression for Spastic Paraplegia 9b, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 9b, Autosomal Recessive.

Pathways for Spastic Paraplegia 9b, Autosomal Recessive

GO Terms for Spastic Paraplegia 9b, Autosomal Recessive

Cellular components related to Spastic Paraplegia 9b, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 8.92 PYCR1 OTC GDAP1 ALDH18A1

Biological processes related to Spastic Paraplegia 9b, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.5 PYCR3 PYCR1 ALDH18A1
2 L-proline biosynthetic process GO:0055129 9.33 PYCR3 PYCR1 ALDH18A1
3 citrulline biosynthetic process GO:0019240 9.26 OTC ALDH18A1
4 cellular amino acid biosynthetic process GO:0008652 9.26 PYCR3 PYCR1 OTC ALDH18A1
5 proline biosynthetic process GO:0006561 8.8 PYCR3 PYCR1 ALDH18A1

Molecular functions related to Spastic Paraplegia 9b, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.33 PYCR3 PYCR1 ALDH18A1
2 identical protein binding GO:0042802 9.26 PYCR3 PYCR1 OTC ALDH18A1
3 pyrroline-5-carboxylate reductase activity GO:0004735 8.62 PYCR3 PYCR1

Sources for Spastic Paraplegia 9b, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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