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ORPHA:357043

Amyotrophic lateral sclerosis type 4

low confidenceDisorder

Also known as: ALS4 · Distal hereditary motor neuropathy with upper motor neuron signs · dHMN with upper motor neuron signs

Query health: suspect — Only one of 3 strategies returned hits (phrase).

Publications

1,648

Trials

0

Interventional, condition-specific

Researchers

1,248

Distinct authors in sample

Gene link

SETX

Definitive

Readiness

3/6

Stages with a signal

Clinical definition (Orphanet)

A rare genetic motor neuron disease characterized by late childhood- or adolescent-onset of slowly , severe, distal limb muscle weakness and wasting, in association with pyramidal signs, normal sensation, and absence of bulbar involvement, leading to degeneration of motor neurons in the brain and spinal cord.

How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (5)

ALS 4 · SETX amyotrophic lateral sclerosis · amyotrophic lateral sclerosis 4, juvenile · amyotrophic lateral sclerosis caused by mutation in SETX · distal hereditary motor neuropathy with upper motor neuron signs

Research stages

Trial readiness signals

Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”

3/6 stages with a signal

No specific-condition interventional trial, but broader-category trials exist — discuss eligibility with a clinician.

  1. Gene identifiedPresent

    Definitive — SETX

  2. LiteraturePresent

    1,648 matched papers (1,137 in last 10 years) Source

  3. Phenotype characterisedNot checked

    Not yet enriched from Monarch / HPO

  4. Animal modelNot checked

    Not yet enriched from Monarch / Alliance

  5. Orphan designationNot checked

    FDA/EMA orphan-drug designation not enriched yet

  6. Interventional trialPartial

    None under the specific name; 676 for broader category amyotrophic lateral sclerosis

Biology

Genes and phenotypes

Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.

Do we know what causes it?

Yes — we know a specific gene responsible (SETX).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

Not enriched in this build — Monarch phenotype joins were not run for this record.

Animal models (Monarch / Alliance)

Not enriched in this build.

Literature

Is anyone studying this?

1,648

1,648 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=5449) is 41.

1,648 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 41 (publications denominator n=5449).

1,137 in the last 10 years · low confidence

Phrase hits: 1,648 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,248

Distinct author names in 200 sampled papers — named people below.

Who's working on it?

No interventional trial matched this name; these authors publish on it in the sampled literature — a practical starting point for contact.

  1. 01
    Chiò A5 papers · 2026

    'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy; Neurology 1, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza of Turin, Turin, Italy. Electronic address: adriano.chio@unito.it.

    Papers in Europe PMC
  2. 02
    Bennett CL4 papers · 2023

    Departments of Pathology, Laboratory Medicine, Neurology, and Biological Chemistry, UCI Center for Neurotherapeutics, University of California Irvine School of Medicine, Irvine, CA, 92697, USA.

    Papers in Europe PMC
  3. 03
    Grunseich C4 papers · 2025

    Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: christopher.grunseich@nih.gov.

    Papers in Europe PMC
  4. 04
    La Spada AR4 papers · 2023

    Departments of Pathology, Laboratory Medicine, Neurology, and Biological Chemistry, UCI Center for Neurotherapeutics, University of California Irvine School of Medicine, Irvine, CA, 92697, USA. alaspada@uci.edu.

    Papers in Europe PMC
  5. 05
    Liu Y4 papers · 2026

    School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.

    Papers in Europe PMC
  6. 06
    Wang Y4 papers · 2026

    Department of Neurology, University of Michigan, Ann Arbor, MI, United States.

    Papers in Europe PMC
  7. 07
    Wu T4 papers · 2026

    State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou, China.

    Papers in Europe PMC
  8. 08
    Zhao Y4 papers · 2026

    Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA.

    Papers in Europe PMC
  9. 09
    Benatar M3 papers · 2025

    Department of Neurology, University of Miami, Miami, Florida, USA.

    Papers in Europe PMC
  10. 10
    Calvo A3 papers · 2025

    ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

0

interventional trials for this specific condition

No interventional trial testing a treatment matched this specific condition name. 1 observational study did — shown below because natural-history and cohort work can be an important step toward a trial. 676 trials are registered for amyotrophic lateral sclerosis, the broader category — shown separately because they may or may not enrol this specific subtype.

Data as of 27 July 2026

No matched interventional trials. This is true for 73% of diseases in the trials denominator (5114 of 7003). Here are the researchers publishing on it.

low confidence · 36.5th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

No interventional trial testing a treatment was found for this specific condition name on ClinicalTrials.gov.

676 interventional trials matched amyotrophic lateral sclerosis, the broader category — listed below. Those studies are not counted in the condition-specific total.

Broader category: amyotrophic lateral sclerosis

676

Interventional trials for the parent category, exclusive of NCT IDs already counted above. Eligibility for this subtype is not guaranteed.

Worth raising with a clinician. How we count trials.

Recruiting under the broader category

Observational and natural-history studies

1 observational study matches this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.

Recruiting or not-yet-recruiting

Open the complete matched search on ClinicalTrials.gov

Where to find support

We do not yet link condition-specific patient organisations. These umbrella groups support undiagnosed and ultra-rare families:

India — NPRD

Last verified 2026-07-26

This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.

Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.

How we counted this

Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.

"Amyotrophic lateral sclerosis type 4" OR "Distal hereditary motor neuropathy with upper motor neuron signs" OR "dHMN with upper motor neuron signs" OR "ALS 4" OR "SETX amyotrophic lateral sclerosis" OR "amyotrophic lateral sclerosis 4, juvenile" OR "amyotrophic lateral sclerosis caused by mutation in SETX"

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Amyotrophic Lateral Sclerosis 4, Juvenile

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"Amyotrophic lateral sclerosis type 4" OR "Distal hereditary motor neuropathy with upper motor neuron signs" OR "dHMN with upper motor neuron signs" OR "ALS 4" OR "SETX amyotrophic lateral sclerosis" OR "amyotrophic lateral sclerosis 4, juvenile" OR "amyotrophic lateral sclerosis caused by mutation in SETX" OR "SETX"

Recall-expansion terms: SETX

Study-type breakdown: 0 interventional · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.

Parent-category trials query:

"amyotrophic lateral sclerosis"

Query health: suspect — strategies attempted: phrase, mesh, recall-expansion; with hits: phrase

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: ALS4

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • 1 synonym(s) dropped by stoplist (may under-count)
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (1648) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T14:31:06.374Z