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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 2 strategies returned hits (phrase).

Publications

3,460

Trials

0

Interventional, condition-specific

Researchers

1,248

Distinct authors in sample

Gene link

SETX

Definitive

Readiness

5/6

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.”

5/6 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

    3,460 matched papers (2,480 in last 10 years) Source

  3. Phenotype characterisedPresent

    25 HPO annotations (e.g. Clonus; Abnormal lower motor neuron morphology; EMG: positive sharp waves) Source

  4. Animal modelPresent

    2 genotype models (Mus musculus) Source

  5. Orphan designationNot found

    No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source

  6. Interventional trialPartial

    None under the specific name; 678 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)

25

Associated phenotypes · MONDO:0011223

  • Clonus
  • Abnormal lower motor neuron morphology
  • EMG: positive sharp waves
  • Pallor of dorsal columns of the spinal cord
  • Gait disturbance

Showing 5 of 25 — open Monarch for the full list.

Animal models (Monarch / Alliance)

2

Model associations linked to this Mondo ID

Monarch fetch 2026-07-29

Therapies

Designations, candidates, and chemicals

FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.

Orphan designation (FDA · EMA)

No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.

Open Targets candidates

No drugs or clinical candidates returned for this Mondo ID on Open Targets.

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

3,460

3,460 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=3967) is 59.

3,460 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).

2,480 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. 678 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 11 September 2026 · last trial check 11 September 2026

No matched interventional trials. This is true for 77.2% of diseases in the trials denominator (5501 of 7126). Here are the researchers publishing on it.

low confidence · 38.6th 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.

678 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

678

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

Other registries (secondary)

Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.

raw 20 · after dedupe 20 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 20 · dropped 0 · fetched 2026-07-30

Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri

No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).

Uncertain / not reviewed (20)

Where to find support

Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.

Orphanet entry for Amyotrophic lateral sclerosis type 4 — check Associations / patient organisations on that page.

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") OR (MESH:"Amyotrophic Lateral Sclerosis 4, Juvenile") OR ("SETX" OR "SETX syndrome" OR "SETX-related")

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"

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; 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 (3460) 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