HSAN1A
MCID: NRP033
MIFTS: 34

Neuropathy, Hereditary Sensory and Autonomic, Type Ia (HSAN1A)

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

Aliases & Classifications for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

MalaCards integrated aliases for Neuropathy, Hereditary Sensory and Autonomic, Type Ia:

Name: Neuropathy, Hereditary Sensory and Autonomic, Type Ia 58 13
Hsan1a 58 12 76
Hereditary Sensory and Autonomic Neuropathy Type 1a 12 15
Hsan Ia 58 76
Hsn Ia 58 76
Hsan1 58 76
Neuropathy, Hereditary Sensory Radicular, Autosomal Dominant, Type 1a 58
Hereditary Sensory Radicular Neuropathy Autosomal Dominant Type 1a 76
Neuropathy, Sensory and Autonomic, Hereditary, Type 1a 41
Hereditary Sensory and Autonomic Neuropathy Type Ia 12
Neuropathy, Hereditary Sensory and Autonomic, 1a 76
Hereditary Sensory Autonomic Neuropathy, Type 1 74
Neuropathy, Hereditary Sensory, Type Ia; Hsn1a 58
Neuropathy, Hereditary Sensory, Type Ia 58
Hereditary Sensory Neuropathy Type Ia 76
Hsn1a 58
Hsn1 76

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
onset in the second to fourth decades of life
one patient with severe congenital onset has been reported
phenotypic overlap with charcot-marie-tooth disease 2b (cmt2b, )


HPO:

33
neuropathy, hereditary sensory and autonomic, type ia:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

Genetics Home Reference : 26 Hereditary sensory neuropathy type IA is a condition characterized by nerve abnormalities in the legs and feet (peripheral neuropathy). Many people with this condition experience prickling or tingling sensations (paresthesias), numbness, and a reduced ability to feel pain and sense hot and cold. Some affected individuals do not lose sensation, but instead feel shooting pains in their legs and feet. As the disorder progresses, the sensory abnormalities can affect the hands, arms, shoulders, joints, and abdomen. Affected individuals may also experience muscle wasting and weakness as they get older. Weakness in the ankle muscles can make walking difficult. As the condition progresses, some people with hereditary sensory neuropathy type IA require wheelchair assistance.

MalaCards based summary : Neuropathy, Hereditary Sensory and Autonomic, Type Ia, also known as hsan1a, is related to hereditary sensory and autonomic neuropathy type 1 and sptlc1-related hereditary sensory neuropathy. An important gene associated with Neuropathy, Hereditary Sensory and Autonomic, Type Ia is SPTLC1 (Serine Palmitoyltransferase Long Chain Base Subunit 1). The drug Serine has been mentioned in the context of this disorder. Affiliated tissues include skin and skeletal muscle, and related phenotypes are sensorineural hearing impairment and skeletal muscle atrophy

Disease Ontology : 12 A hereditary sensory and autonomic neuropathy type 1 characterized by onset of sensorimotor axonal neuropathy in the first or second decades of life that has material basis in heterozygous mutation in the SPTLC1 gene on chromosome 9q22.

OMIM : 58 The hereditary sensory and autonomic neuropathies (HSAN), which are also referred to as hereditary sensory neuropathies (HSN) in the absence of significant autonomic features, are a genetically and clinically heterogeneous group of disorders associated with sensory dysfunction. HSAN1 is a dominantly inherited sensorimotor axonal neuropathy with onset in the first or second decades of life. (162400)

UniProtKB/Swiss-Prot : 76 Neuropathy, hereditary sensory and autonomic, 1A: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by prominent sensory abnormalities with a variable degree of motor and autonomic dysfunction. The neurological phenotype is often complicated by severe infections, osteomyelitis, and amputations. HSAN1A is an autosomal dominant axonal form with onset in the second or third decades. Initial symptoms are loss of pain, touch, heat, and cold sensation over the feet, followed by distal muscle wasting and weakness. Loss of pain sensation leads to chronic skin ulcers and distal amputations.

Related Diseases for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

Diseases in the Neuropathy, Hereditary Sensory and Autonomic, Type Iia family:

Neuropathy, Hereditary Sensory and Autonomic, Type Ia Neuropathy, Hereditary Sensory and Autonomic, Type Iii
Neuropathy, Hereditary Sensory and Autonomic, Type V Neuropathy, Hereditary Sensory and Autonomic, Type Iib
Neuropathy, Hereditary Sensory and Autonomic, Type Ic Neuropathy, Hereditary Sensory and Autonomic, Type Vi
Neuropathy, Hereditary Sensory and Autonomic, Type Vii Neuropathy, Hereditary Sensory and Autonomic, Type Viii
Hereditary Sensory and Autonomic Neuropathy Type 1

Diseases related to Neuropathy, Hereditary Sensory and Autonomic, Type Ia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 hereditary sensory and autonomic neuropathy type 1 11.9
2 sptlc1-related hereditary sensory neuropathy 11.3
3 indifference to pain, congenital, autosomal recessive 11.1
4 neuropathy, hereditary sensory and autonomic, type iib 11.1
5 neuropathy, hereditary sensory, type iic 11.1
6 neuropathy, hereditary sensory and autonomic, type vi 11.1
7 neuropathy, hereditary sensory and autonomic, type i, with cough and gastroesophageal reflux 11.1
8 neuropathy, hereditary sensory, type id 11.1
9 neuropathy, hereditary sensory, type ie 11.1
10 neuropathy, hereditary sensory, type if 11.1
11 neuropathy, hereditary sensory and autonomic, type viii 11.1
12 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
13 dementia 10.1
14 hereditary sensory neuropathy 10.1
15 sensory peripheral neuropathy 10.1
16 neuropathy 10.1
17 neurogenic arthropathy 9.7 NAA50 SPTLC1
18 tabes dorsalis 9.7 NAA50 SPTLC1
19 tertiary neurosyphilis 9.6 NAA50 SPTLC1
20 peripheral nervous system disease 9.5 NAA50 SPTLC1

Graphical network of the top 20 diseases related to Neuropathy, Hereditary Sensory and Autonomic, Type Ia:



Diseases related to Neuropathy, Hereditary Sensory and Autonomic, Type Ia

Symptoms & Phenotypes for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

Human phenotypes related to Neuropathy, Hereditary Sensory and Autonomic, Type Ia:

33 (show all 14)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 33 HP:0000407
2 skeletal muscle atrophy 33 HP:0003202
3 pes cavus 33 HP:0001761
4 areflexia 33 HP:0001284
5 hyporeflexia 33 HP:0001265
6 abnormality of the skin 33 HP:0000951
7 distal muscle weakness 33 HP:0002460
8 distal sensory loss of all modalities 33 HP:0006984
9 distal sensory impairment 33 HP:0002936
10 foot osteomyelitis 33 HP:0001886
11 chronic axonal neuropathy 33 HP:0007267
12 decreased sensory nerve conduction velocity 33 HP:0003448
13 decreased number of large peripheral myelinated nerve fibers 33 HP:0003387
14 autoamputation of foot 33 HP:0001868

Symptoms via clinical synopsis from OMIM:

58
Skeletal Feet:
pes cavus
autoamputation
osteomyelitis or necrosis, distal, due to sensory neuropathy

Head And Neck Ears:
deafness, sensorineural (reported in 1 family)

Neurologic Peripheral Nervous System:
distal sensory loss of all modalities (pain, temperature, touch, vibration)
taste is spared
sharp, 'lightning'-like pain
distal limb muscular atrophy due to peripheral neuropathy
distal limb muscular weakness due to peripheral neuropathy
more
Skeletal Hands:
autoamputation
osteomyelitis or necrosis, distal, due to sensory neuropathy

Skin Nails Hair Skin:
ulcers, distal, painless, due to sensory neuropathy

Clinical features from OMIM:

162400

Drugs & Therapeutics for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

Drugs for Neuropathy, Hereditary Sensory and Autonomic, Type Ia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Serine Approved, Nutraceutical Phase 1, Phase 2 56-45-1 5951

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 L-Serine Supplementation in Hereditary Sensory Neuropathy Type 1 Completed NCT01733407 Phase 1, Phase 2 L-serine;placebo
2 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

Genetic Tests for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

Anatomical Context for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

MalaCards organs/tissues related to Neuropathy, Hereditary Sensory and Autonomic, Type Ia:

42
Skin, Skeletal Muscle

Publications for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

Articles related to Neuropathy, Hereditary Sensory and Autonomic, Type Ia:

# Title Authors Year
1
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. ( 22045570 )
2011

Variations for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

UniProtKB/Swiss-Prot genetic disease variations for Neuropathy, Hereditary Sensory and Autonomic, Type Ia:

76
# Symbol AA change Variation ID SNP ID
1 SPTLC1 p.Cys133Trp VAR_011392 rs119482082
2 SPTLC1 p.Cys133Tyr VAR_011393 rs119482081
3 SPTLC1 p.Val144Asp VAR_011394 rs119482083
4 SPTLC1 p.Ser331Phe VAR_066245 rs267607087
5 SPTLC1 p.Ala352Val VAR_066246 rs267607088

ClinVar genetic disease variations for Neuropathy, Hereditary Sensory and Autonomic, Type Ia:

6 (show top 50) (show all 142)
# Gene Variation Type Significance SNP ID Assembly Location
1 SPTLC1 NM_006415.3(SPTLC1): c.1072G> C (p.Glu358Gln) single nucleotide variant Likely pathogenic rs797045071 GRCh37 Chromosome 9, 94809463: 94809463
2 SPTLC1 NM_006415.3(SPTLC1): c.1072G> C (p.Glu358Gln) single nucleotide variant Likely pathogenic rs797045071 GRCh38 Chromosome 9, 92047181: 92047181
3 SPTLC1 NM_006415.3(SPTLC1): c.398G> A (p.Cys133Tyr) single nucleotide variant Pathogenic rs119482081 GRCh37 Chromosome 9, 94842327: 94842327
4 SPTLC1 NM_006415.3(SPTLC1): c.398G> A (p.Cys133Tyr) single nucleotide variant Pathogenic rs119482081 GRCh38 Chromosome 9, 92080045: 92080045
5 SPTLC1 NM_006415.3(SPTLC1): c.431T> A (p.Val144Asp) single nucleotide variant Likely pathogenic rs119482083 GRCh37 Chromosome 9, 94830377: 94830377
6 SPTLC1 NM_006415.3(SPTLC1): c.431T> A (p.Val144Asp) single nucleotide variant Likely pathogenic rs119482083 GRCh38 Chromosome 9, 92068095: 92068095
7 SPTLC1 NM_006415.3(SPTLC1): c.1160G> C (p.Gly387Ala) single nucleotide variant Likely benign rs119482084 GRCh37 Chromosome 9, 94800624: 94800624
8 SPTLC1 NM_006415.3(SPTLC1): c.1160G> C (p.Gly387Ala) single nucleotide variant Likely benign rs119482084 GRCh38 Chromosome 9, 92038342: 92038342
9 SPTLC1 NM_006415.3(SPTLC1): c.399T> G (p.Cys133Trp) single nucleotide variant Pathogenic rs119482082 GRCh37 Chromosome 9, 94842326: 94842326
10 SPTLC1 NM_006415.3(SPTLC1): c.399T> G (p.Cys133Trp) single nucleotide variant Pathogenic rs119482082 GRCh38 Chromosome 9, 92080044: 92080044
11 SPTLC1 NM_006415.3(SPTLC1): c.1055C> T (p.Ala352Val) single nucleotide variant Pathogenic rs267607088 GRCh37 Chromosome 9, 94809480: 94809480
12 SPTLC1 NM_006415.3(SPTLC1): c.1055C> T (p.Ala352Val) single nucleotide variant Pathogenic rs267607088 GRCh38 Chromosome 9, 92047198: 92047198
13 SPTLC1 NM_006415.3(SPTLC1): c.560+16G> C single nucleotide variant Benign rs73512337 GRCh37 Chromosome 9, 94830232: 94830232
14 SPTLC1 NM_006415.3(SPTLC1): c.560+16G> C single nucleotide variant Benign rs73512337 GRCh38 Chromosome 9, 92067950: 92067950
15 SPTLC1 NM_006415.3(SPTLC1): c.781-6A> G single nucleotide variant Benign/Likely benign rs138268337 GRCh37 Chromosome 9, 94812355: 94812355
16 SPTLC1 NM_006415.3(SPTLC1): c.781-6A> G single nucleotide variant Benign/Likely benign rs138268337 GRCh38 Chromosome 9, 92050073: 92050073
17 SPTLC1 NM_006415.3(SPTLC1): c.208G> T (p.Val70Phe) single nucleotide variant Uncertain significance rs764460003 GRCh37 Chromosome 9, 94871074: 94871074
18 SPTLC1 NM_006415.3(SPTLC1): c.208G> T (p.Val70Phe) single nucleotide variant Uncertain significance rs764460003 GRCh38 Chromosome 9, 92108792: 92108792
19 SPTLC1 NM_006415.3(SPTLC1): c.1411G> A (p.Val471Ile) single nucleotide variant Benign/Likely benign rs141292904 GRCh37 Chromosome 9, 94794758: 94794758
20 SPTLC1 NM_006415.3(SPTLC1): c.1411G> A (p.Val471Ile) single nucleotide variant Benign/Likely benign rs141292904 GRCh38 Chromosome 9, 92032476: 92032476
21 SPTLC1 NM_006415.3(SPTLC1): c.*631G> C single nucleotide variant Uncertain significance rs1057515686 GRCh38 Chromosome 9, 92031834: 92031834
22 SPTLC1 NM_006415.3(SPTLC1): c.*631G> C single nucleotide variant Uncertain significance rs1057515686 GRCh37 Chromosome 9, 94794116: 94794116
23 SPTLC1 NM_006415.3(SPTLC1): c.*605T> C single nucleotide variant Uncertain significance rs1057515687 GRCh37 Chromosome 9, 94794142: 94794142
24 SPTLC1 NM_006415.3(SPTLC1): c.*605T> C single nucleotide variant Uncertain significance rs1057515687 GRCh38 Chromosome 9, 92031860: 92031860
25 SPTLC1 NM_006415.3(SPTLC1): c.*483A> G single nucleotide variant Likely benign rs541284488 GRCh37 Chromosome 9, 94794264: 94794264
26 SPTLC1 NM_006415.3(SPTLC1): c.*483A> G single nucleotide variant Likely benign rs541284488 GRCh38 Chromosome 9, 92031982: 92031982
27 SPTLC1 NM_006415.3(SPTLC1): c.*190A> C single nucleotide variant Likely benign rs552433019 GRCh37 Chromosome 9, 94794557: 94794557
28 SPTLC1 NM_006415.3(SPTLC1): c.*190A> C single nucleotide variant Likely benign rs552433019 GRCh38 Chromosome 9, 92032275: 92032275
29 SPTLC1 NM_006415.3(SPTLC1): c.1136+12A> G single nucleotide variant Benign rs76562923 GRCh37 Chromosome 9, 94808269: 94808269
30 SPTLC1 NM_006415.3(SPTLC1): c.1136+12A> G single nucleotide variant Benign rs76562923 GRCh38 Chromosome 9, 92045987: 92045987
31 SPTLC1 NM_006415.3(SPTLC1): c.387C> T (p.Gly129=) single nucleotide variant Benign/Likely benign rs141265918 GRCh37 Chromosome 9, 94842338: 94842338
32 SPTLC1 NM_006415.3(SPTLC1): c.387C> T (p.Gly129=) single nucleotide variant Benign/Likely benign rs141265918 GRCh38 Chromosome 9, 92080056: 92080056
33 SPTLC1 NM_006415.3(SPTLC1): c.*1009G> T single nucleotide variant Likely benign rs559735773 GRCh38 Chromosome 9, 92031456: 92031456
34 SPTLC1 NM_006415.3(SPTLC1): c.*1009G> T single nucleotide variant Likely benign rs559735773 GRCh37 Chromosome 9, 94793738: 94793738
35 SPTLC1 NM_006415.3(SPTLC1): c.*750C> T single nucleotide variant Uncertain significance rs768395365 GRCh37 Chromosome 9, 94793997: 94793997
36 SPTLC1 NM_006415.3(SPTLC1): c.*750C> T single nucleotide variant Uncertain significance rs768395365 GRCh38 Chromosome 9, 92031715: 92031715
37 SPTLC1 NM_006415.3(SPTLC1): c.*451G> A single nucleotide variant Uncertain significance rs868416931 GRCh37 Chromosome 9, 94794296: 94794296
38 SPTLC1 NM_006415.3(SPTLC1): c.*451G> A single nucleotide variant Uncertain significance rs868416931 GRCh38 Chromosome 9, 92032014: 92032014
39 SPTLC1 NM_006415.3(SPTLC1): c.*445A> G single nucleotide variant Likely benign rs7944 GRCh37 Chromosome 9, 94794302: 94794302
40 SPTLC1 NM_006415.3(SPTLC1): c.*445A> G single nucleotide variant Likely benign rs7944 GRCh38 Chromosome 9, 92032020: 92032020
41 SPTLC1 NM_006415.3(SPTLC1): c.*200G> T single nucleotide variant Uncertain significance rs1057515689 GRCh37 Chromosome 9, 94794547: 94794547
42 SPTLC1 NM_006415.3(SPTLC1): c.*200G> T single nucleotide variant Uncertain significance rs1057515689 GRCh38 Chromosome 9, 92032265: 92032265
43 SPTLC1 NM_006415.3(SPTLC1): c.*124A> G single nucleotide variant Likely benign rs189582528 GRCh37 Chromosome 9, 94794623: 94794623
44 SPTLC1 NM_006415.3(SPTLC1): c.*124A> G single nucleotide variant Likely benign rs189582528 GRCh38 Chromosome 9, 92032341: 92032341
45 SPTLC1 NM_006415.3(SPTLC1): c.1137-15_1137-14dupGT duplication Likely benign rs147137401 GRCh37 Chromosome 9, 94800661: 94800662
46 SPTLC1 NM_006415.3(SPTLC1): c.1137-15_1137-14dupGT duplication Likely benign rs147137401 GRCh38 Chromosome 9, 92038379: 92038380
47 SPTLC1 NM_006415.3(SPTLC1): c.58-9C> T single nucleotide variant Uncertain significance rs769188151 GRCh37 Chromosome 9, 94874853: 94874853
48 SPTLC1 NM_006415.3(SPTLC1): c.58-9C> T single nucleotide variant Uncertain significance rs769188151 GRCh38 Chromosome 9, 92112571: 92112571
49 SPTLC1 NM_006415.3(SPTLC1): c.-27C> T single nucleotide variant Uncertain significance rs558203491 GRCh37 Chromosome 9, 94877679: 94877679
50 SPTLC1 NM_006415.3(SPTLC1): c.-27C> T single nucleotide variant Uncertain significance rs558203491 GRCh38 Chromosome 9, 92115397: 92115397

Expression for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

Search GEO for disease gene expression data for Neuropathy, Hereditary Sensory and Autonomic, Type Ia.

Pathways for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

GO Terms for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

Molecular functions related to Neuropathy, Hereditary Sensory and Autonomic, Type Ia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 8.96 NAA50 SPTLC1
2 transferase activity, transferring acyl groups GO:0016746 8.62 NAA50 SPTLC1

Sources for Neuropathy, Hereditary Sensory and Autonomic, Type Ia

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