ORPHA:803
Amyotrophic lateral sclerosis
Synonyms: ALS · Charcot disease · Lou Gehrig disease
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal dominant, Autosomal recessive, Multigenic/multifactorial, X-linked dominant
- Age of onset
- Adult
- Status
- active
A rare neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord.
1
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Amyotrophic lateral sclerosis | ALS · Charcot disease · Lou Gehrig disease |
| fr | Sclérose latérale amyotrophique | Maladie de Charcot · Maladie de Lou Gehrig · SLA |
| de | Amyotrophe Lateralsklerose | Charcot-Krankheit · Lou-Gehrig-Krankheit |
| es | Esclerosis lateral amiotrófica | ELA · Enfermedad de Charcot · Enfermedad de Lou-Gehrig |
| it | Sclerosi laterale amiotrofica | Malattia di Charcot · Malattia di Lou-Gehrig |
| nl | Amyotrofische laterale sclerose | ALS · Amyotrofe laterale sclerose · Ziekte van Charcot · Ziekte van Lou Gehrig |
| pt | Esclerose lateral amiotrófica | Doença de Charcot · Doença de Lou-Gehrig · ELA |
| pl | Stwardnienie zanikowe boczne | ALS · Choroba Charcota · Choroba Lou Gehriga |
| cs | Amyotrofická laterální skleróza | ALS · Charcotova nemoc · Lou Gehrigova nemoc |
| uk | Бічний аміотрофічний склероз | ALS · Хвороба Шарко · Хвороба Лу Геріга |
| zh | 肌萎缩侧索硬化 | Lou Gehrig病 |
| tr | Amyotrofik lateral skleroz | ALS · Charcot hastalığı · Lou Gehrig hastalığı |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 105400 | E | validated | |
| OMIM | 205250 | BTNT | validated | |
| OMIM | 300857 | NTBT | validated | |
| OMIM | 600795 | BTNT | validated | |
| OMIM | 606070 | BTNT | validated | |
| OMIM | 606640 | BTNT | validated | |
| OMIM | 608030 | BTNT | validated | |
| OMIM | 608031 | BTNT | validated | |
| OMIM | 608627 | BTNT | validated | |
| OMIM | 611895 | BTNT | validated | |
| OMIM | 612069 | BTNT | validated | |
| OMIM | 612577 | BTNT | validated | |
| OMIM | 613435 | BTNT | validated | |
| OMIM | 613954 | BTNT | validated | |
| OMIM | 614808 | BTNT | validated | |
| OMIM | 615426 | BTNT | validated | |
| OMIM | 615515 | BTNT | validated | |
| OMIM | 616208 | BTNT | validated | |
| OMIM | 616437 | BTNT | validated | |
| OMIM | 617839 | BTNT | validated | |
| OMIM | 617892 | BTNT | validated | |
| OMIM | 617921 | BTNT | validated | |
| OMIM | 619133 | BTNT | validated | |
| OMIM | 619141 | BTNT | validated | |
| OMIM | 620452 | BTNT | validated | |
| ICD-10 | G12.2 | NTBT | inclusion | validated |
| ICD-11 | 8B60.0 | E | specific | validated |
| MONDO | 0004976 | E | validated | |
| MeSH | D000690 | E | validated | |
| UMLS | C0002736 | E | validated | |
| GARD | 5786 | E | validated | |
| MedDRA | 10002026 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
3
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (3):
- ORPHA:183500Genetic neurodegenerative disease
rare genetic diseases - ORPHA:98503Motor neuron disease
rare neurological diseases - ORPHA:182070Rare neurodegenerative disease
rare neurological diseases
No children.
4
Genes
33 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| DCTN1 | Candidate gene tested in | Not yet assessed | HGNC:2711 | ENSG00000204843 | 601143 | 2p13.1 | dynactin subunit 1 | 23941283[PMID] |
| TAF15 | Candidate gene tested in | Not yet assessed | HGNC:11547 | ENSG00000270647 | 601574 | 17q12 | TATA-box binding protein associated factor 15 | 21438137[PMID] |
| ANG | Disease-causing germline mutation(s) in | Assessed | HGNC:483 | ENSG00000214274 | 105850 | 14q11.2 | angiogenin | 23941283[PMID]_20301623[PMID] |
| ANXA11 | Disease-causing germline mutation(s) in | Assessed | HGNC:535 | ENSG00000122359 | 602572 | 10q22.3 | annexin A11 | 28469040[PMID] |
| C9ORF72 | Disease-causing germline mutation(s) in | Assessed | HGNC:28337 | ENSG00000147894 | 614260 | 9p21.2 | C9orf72-SMCR8 complex subunit | 24085347[PMID] |
| CCNF | Disease-causing germline mutation(s) in | Assessed | HGNC:1591 | ENSG00000162063 | 600227 | 16p13.3 | cyclin F | 27080313[PMID] |
| CFAP410 | Disease-causing germline mutation(s) in | Assessed | HGNC:1260 | ENSG00000160226 | 603191 | 21q22.3 | cilia and flagella associated protein 410 | 27455348[PMID]_26974433[PMID] |
| CHCHD10 | Disease-causing germline mutation(s) in | Assessed | HGNC:15559 | ENSG00000250479 | 615903 | 22q11.23 | coiled-coil-helix-coiled-coil-helix domain containing 10 | 25113787[PMID]_25261972[PMID]_25113788[PMID]_25261971[PMID]_25348631[PMID]_25348633[PMID]_25155093[PMID] |
| CHMP2B | Disease-causing germline mutation(s) in | Assessed | HGNC:24537 | ENSG00000083937 | 609512 | 3p11.2 | charged multivesicular body protein 2B | 20352044[PMID]_23155438[PMID]_16807408[PMID] |
| DAO | Disease-causing germline mutation(s) in | Assessed | HGNC:2671 | ENSG00000110887 | 124050 | 12q24.11 | D-amino acid oxidase | 24085347[PMID]_20368421[PMID] |
| ERBB4 | Disease-causing germline mutation(s) in | Assessed | HGNC:3432 | ENSG00000178568 | 600543 | 2q34 | erb-b2 receptor tyrosine kinase 4 | 24119685[PMID] |
| FIG4 | Disease-causing germline mutation(s) in | Assessed | HGNC:16873 | ENSG00000112367 | 609390 | 6q21 | FIG4 phosphoinositide 5-phosphatase | 24085347[PMID] |
| FUS | Disease-causing germline mutation(s) in | Assessed | HGNC:4010 | ENSG00000089280 | 137070 | 16p11.2 | FUS RNA binding protein | 24085347[PMID] |
| GLE1 | Disease-causing germline mutation(s) in | Assessed | HGNC:4315 | ENSG00000119392 | 603371 | 9q34.11 | GLE1 RNA export mediator | 25343993[PMID] |
| HNRNPA1 | Disease-causing germline mutation(s) in | Assessed | HGNC:5031 | ENSG00000135486 | 164017 | 12q13.13 | heterogeneous nuclear ribonucleoprotein A1 | 23455423[PMID] |
| LRP12 | Disease-causing germline mutation(s) in | Assessed | HGNC:31708 | ENSG00000147650 | 618299 | 8q22.3 | LDL receptor related protein 12 | 37339631[PMID] |
| MATR3 | Disease-causing germline mutation(s) in | Assessed | HGNC:6912 | ENSG00000015479 | 164015 | 5q31.2 | matrin 3 | 24686783[PMID] |
| OPTN | Disease-causing germline mutation(s) in | Assessed | HGNC:17142 | ENSG00000123240 | 602432 | 10p13 | optineurin | 24085347[PMID] |
| PFN1 | Disease-causing germline mutation(s) in | Assessed | HGNC:8881 | ENSG00000108518 | 176610 | 17p13.2 | profilin 1 | 22801503[PMID]_23428184[PMID]_24085347[PMID] |
| SOD1 | Disease-causing germline mutation(s) in | Assessed | HGNC:11179 | ENSG00000142168 | 147450 | 21q22.11 | superoxide dismutase 1 | 20301623[PMID]_23941283[PMID] |
| SQSTM1 | Disease-causing germline mutation(s) in | Assessed | HGNC:11280 | ENSG00000161011 | 601530 | 5q35.3 | sequestosome 1 | 23303844[PMID]_24138988[PMID]_22084127[PMID]_24085347[PMID] |
| TARDBP | Disease-causing germline mutation(s) in | Assessed | HGNC:11571 | ENSG00000120948 | 605078 | 1p36.22 | TAR DNA binding protein | 24085347[PMID] |
| UBQLN2 | Disease-causing germline mutation(s) in | Assessed | HGNC:12509 | ENSG00000188021 | 300264 | Xp11.21 | ubiquilin 2 | 24085347[PMID] |
| VAPB | Disease-causing germline mutation(s) in | Assessed | HGNC:12649 | ENSG00000124164 | 605704 | 20q13.32 | VAMP associated protein B and C | 20301623[PMID]_23941283[PMID] |
| VCP | Disease-causing germline mutation(s) in | Assessed | HGNC:12666 | ENSG00000165280 | 601023 | 9p13.3 | valosin containing protein | 24085347[PMID] |
| ATXN2 | Major susceptibility factor in | Assessed | HGNC:10555 | ENSG00000204842 | 601517 | 12q24.12 | ataxin 2 | 24085347[PMID] |
| GLT8D1 | Major susceptibility factor in | Assessed | HGNC:24870 | ENSG00000016864 | 618399 | 3p21.1 | glycosyltransferase 8 domain containing 1 | 30811981[PMID] |
| NEFH | Major susceptibility factor in | Assessed | HGNC:7737 | ENSG00000100285 | 162230 | 22q12.2 | neurofilament heavy chain | 23941283[PMID] |
| NEK1 | Major susceptibility factor in | Assessed | HGNC:7744 | ENSG00000137601 | 604588 | 4q33 | NIMA related kinase 1 | 26945885[PMID] |
| PRPH | Major susceptibility factor in | Assessed | HGNC:9461 | ENSG00000135406 | 170710 | 12q13.12 | peripherin | 20363051[PMID] |
| TBK1 | Major susceptibility factor in | Assessed | HGNC:11584 | ENSG00000183735 | 604834 | 12q14.2 | TANK binding kinase 1 | 25700176[PMID] |
| TREM2 | Major susceptibility factor in | Assessed | HGNC:17761 | ENSG00000095970 | 605086 | 6p21.1 | triggering receptor expressed on myeloid cells 2 | 24535663[PMID] |
| UNC13A | Major susceptibility factor in | Assessed | HGNC:23150 | ENSG00000130477 | 609894 | 19p13.11 | unc-13 homolog A | 24931836[PMID]_19734901[PMID] |
5
Prevalence and incidence
33 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Annual incidence | 1-9 / 100 000 | 2.2 / 100 000 | Europe | Value and class | Validated | 19710046[PMID]_[EXPERT] |
| Point prevalence | 1-9 / 100 000 | 5.2 / 100 000 | Europe | Value and class | Validated | 19192301[PMID]_[EXPERT] |
| Point prevalence | 1-9 / 100 000 | 3.85 / 100 000 | Worldwide | Value and class | Not yet validated | 21665992[PMID] |
| Annual incidence | 1-9 / 100 000 | 1.35 / 100 000 | Worldwide | Value and class | Not yet validated | 21665992[PMID] |
| Annual incidence | 1-9 / 100 000 | 1.06 / 100 000 | United Kingdom | Value and class | Validated | 17898523[PMID]_17219036[PMID] |
| Point prevalence | 1-9 / 100 000 | 4.9 / 100 000 | United Kingdom | Value and class | Validated | 17898523[PMID] |
| Annual incidence | 1-9 / 100 000 | 2.1 / 100 000 | Ireland | Value and class | Validated | 10025778[PMID] |
| Point prevalence | 1-9 / 100 000 | 4.7 / 100 000 | Ireland | Value and class | Validated | 10025778[PMID] |
| Annual incidence | 1-9 / 100 000 | 2.4 / 100 000 | Finland | Value and class | Validated | 6601351[PMID] |
| Point prevalence | 1-9 / 100 000 | 6.4 / 100 000 | Finland | Value and class | Validated | 6601351[PMID] |
| Annual incidence | 1-9 / 100 000 | 2 / 100 000 | Canada | Value and class | Not yet validated | 3762972[PMID]_19494548[PMID]_ ORPHANET |
| Point prevalence | 1-9 / 100 000 | 4.9 / 100 000 | Canada | Value and class | Validated | 3762972[PMID] |
| Annual incidence | 1-9 / 100 000 | 1.46 / 100 000 | United States | Value and class | Validated | 25298019[PMID] |
| Annual incidence | 1-9 / 100 000 | 1.37 / 100 000 | Uruguay | Value and class | Validated | 18334826[PMID] |
| Point prevalence | 1-9 / 100 000 | 1.9 / 100 000 | Uruguay | Value and class | Validated | 18334826[PMID] |
| Annual incidence | 1-9 / 100 000 | 1.4 / 100 000 | Denmark | Value and class | Validated | 2786160[PMID] |
| Point prevalence | 1-9 / 100 000 | 3.1 / 100 000 | Denmark | Value and class | Validated | 2786160[PMID] |
| Annual incidence | 1-9 / 100 000 | 3 / 100 000 | Italy | Value and class | Validated | 19237701[PMID] |
| Point prevalence | 1-9 / 100 000 | 7.9 / 100 000 | Italy | Value and class | Not yet validated | 19237701[PMID] |
| Annual incidence | 1-9 / 100 000 | 2 / 100 000 | France | Value and class | Validated | 19452307[PMID] |
| Annual incidence | 1-9 / 100 000 | 1.4 / 100 000 | Spain | Value and class | Validated | 23286747[PMID] |
| Point prevalence | 1-9 / 100 000 | 5.4 / 100 000 | Spain | Value and class | Validated | 23286747[PMID] |
| Annual incidence | 1-9 / 100 000 | 2.2 / 100 000 | Norway | Value and class | Validated | 21860251[PMID] |
| Point prevalence | 1-9 / 100 000 | 4 / 100 000 | Norway | Value and class | Validated | 21860251[PMID] |
| Annual incidence | 1-9 / 1 000 000 | 0.51 / 100 000 | Taiwan, Province of China | Value and class | Validated | DOI:10.1016/j.jfma.2013.01.008[OTHER] |
| Point prevalence | 1-9 / 100 000 | 1.97 / 100 000 | Taiwan, Province of China | Value and class | Validated | DOI:10.1016/j.jfma.2013.01.008[OTHER] |
| Annual incidence | 1-9 / 100 000 | 2.6 / 100 000 | Faroe Islands | Value and class | Validated | 22034926[PMID] |
| Annual incidence | 1-9 / 1 000 000 | 0.42 / 100 000 | Iran, Islamic Republic of | Value and class | Validated | 20214678[PMID] |
| Point prevalence | 1-9 / 100 000 | 1.57 / 100 000 | Iran, Islamic Republic of | Value and class | Validated | 20214678[PMID] |
| Annual incidence | 1-9 / 100 000 | 2.5 / 100 000 | Specific population | Value and class | Validated | 23052600[PMID] |
| Point prevalence | 1-5 / 10 000 | 10.8 / 100 000 | Specific population | Value and class | Validated | 23052600[PMID] |
| Annual incidence | 1-9 / 100 000 | 1.4 / 100 000 | Specific population | Value and class | Validated | 22409362[PMID] |
| Point prevalence | 1-9 / 100 000 | 6 / 100 000 | Specific population | Value and class | Validated | 22409362[PMID] |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
6
HPO phenotypes
47 annotations · validated 2023-09-05| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Obligate (100%) | ||
| HP:0007354 | Amyotrophic lateral sclerosis | |
| Very frequent (99-80%) | ||
| HP:0003324 | Generalized muscle weakness | |
| HP:0007373 | Motor neuron atrophy | |
| HP:0002180 | Neurodegeneration | |
| Frequent (79-30%) | ||
| HP:0030878 | Abnormality on pulmonary function testing | |
| HP:0000739 | Anxiety | |
| HP:0000708 | Atypical behavior | |
| HP:0003487 | Babinski sign | |
| HP:0100543 | Cognitive impairment | |
| HP:0000716 | Depression | |
| HP:0003693 | Distal amyotrophy | |
| HP:0002307 | Drooling | |
| HP:0001260 | Dysarthria | |
| HP:0002015 | Dysphagia | |
| HP:0001618 | Dysphonia | |
| HP:0002094 | Dyspnea | |
| HP:0000712 | Emotional lability | |
| HP:0002380 | Fasciculations | |
| HP:0030192 | Fatigable weakness of bulbar muscles | |
| HP:0030196 | Fatigable weakness of respiratory muscles | |
| HP:0030195 | Fatigable weakness of swallowing muscles | |
| HP:0012378 | Fatigue | |
| HP:0031993 | Hoffmann sign | |
| HP:0001347 | Hyperreflexia | |
| HP:0007340 | Lower limb muscle weakness | |
| HP:0003394 | Muscle spasm | |
| HP:0012531 | Pain | |
| HP:0003470 | Paralysis | |
| HP:0008955 | Progressive distal muscular atrophy | |
| HP:0002878 | Respiratory failure | |
| HP:0003202 | Skeletal muscle atrophy | |
| HP:0001257 | Spasticity | |
| HP:0012473 | Tongue atrophy | |
| HP:0003484 | Upper limb muscle weakness | |
| HP:0001824 | Weight loss | |
| HP:0000217 | Xerostomia | |
| Occasional (29-5%) | ||
| HP:0004326 | Cachexia | |
| HP:0009027 | Foot dorsiflexor weakness | |
| HP:0002145 | Frontotemporal dementia | |
| HP:0033683 | Jaw hyperreflexia | |
| HP:0002463 | Language impairment | |
| HP:0012764 | Orthopnea | |
| HP:0002360 | Sleep abnormality | |
| HP:0002313 | Spastic paraparesis | |
| HP:0003376 | Steppage gait | |
| HP:0001308 | Tongue fasciculations | |
| Very rare (<4-1%) | ||
| HP:0025425 | Laryngospasm | |
Run the differential on the 4 obligate / very frequent terms
Annotation source: 27514291[PMID]_36116464[PMID]_28552366[PMID]_30207670[PMID]
7
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/803
- This record as JSON: /data/d/803.json