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ORPHA:436166

Periodic fever-infantile enterocolitis-autoinflammatory syndrome

low confidenceDisorder

Also known as: NLRC4-related autoinflammatory syndrome with macrophage activation syndrome · NLRC4-related infantile enterocolitis-autoinflammatory syndrome · NLRC4-related macrophage activation syndrome · NLRC4-related MAS · NLRC4-related autoinflammatory syndrome with MAS

Publications

9,075

Trials

1

Interventional, condition-specific

Researchers

1,336

Distinct authors in sample

Gene link

NLRC4

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare genetic systemic or rheumatologic disease characterized by or onset of enterocolitis (which resolves with age), periodic fever, and episodes of severe systemic inflammation, which may be precipitated by infections, stress, or fatigue. Signs and symptoms include , urticaria-like rashes, arthralgia, and myalgia. Associated laboratory findings are elevated inflammatory markers (such as ferritin, C-reactive protein), pancytopenia, and elevated transaminases. If left untreated, flares can progress to coagulopathy, organ failure, and death.

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 (2)

Autoinflammation with Infantile Enterocolitis · autoinflammation with infantile enterocolitis

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.”

4/6 stages with a signal

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Definitive — NLRC4

  2. LiteraturePresent

    9,075 matched papers (7,210 in last 10 years) Source

  3. Phenotype characterisedPresent

    28 HPO annotations (e.g. Reduced total natural killer cell count; Fatigue; Villous atrophy) Source

  4. Animal modelNot found

    No Alliance genotype “model of” associations via Monarch for these Mondo IDs

  5. Orphan designationNot found

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

  6. Interventional trialPresent

    1 matched on ClinicalTrials.gov

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 (NLRC4).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

28

Associated phenotypes · MONDO:0014472

  • Reduced total natural killer cell count
  • Fatigue
  • Villous atrophy
  • Thrombocytopenia
  • Enterocolitis

Showing 5 of 28 — open Monarch for the full list.

Animal models (Monarch / Alliance)

None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.

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?

9,075

9,075 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

9,075 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).

7,210 in the last 10 years · low confidence

Phrase hits: 356 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,336

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

Who's working on it?

People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.

  1. 01
    Wang Y9 papers · 2026

    Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

    Papers in Europe PMC
  2. 02
    Canna SW5 papers · 2025

    Pediatric Rheumatology/RK Mellon Institute, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pa.

    Papers in Europe PMC
  3. 03
    Li Y5 papers · 2023

    Department of Stomatology, Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an, Shaanxi, China.

    Papers in Europe PMC
  4. 04
    Kang Z4 papers · 2026

    Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.

    Papers in Europe PMC
  5. 05
    Li J4 papers · 2026

    Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

    Papers in Europe PMC
  6. 06
    Li X4 papers · 2026

    Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

    Papers in Europe PMC
  7. 07
    Belot A3 papers · 2023

    Pediatric Nephrology, Rheumatology, Dermatology, HFME, Hospices Civils de Lyon, National Referee Centre RAISE, & INSERM U1111, Université de Lyon, Lyon, France.

    Papers in Europe PMC
  8. 08
    Eleftheriou D3 papers · 2023

    Inflammation and Rheumatology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.

    Papers in Europe PMC
  9. 09
    Gabay C3 papers · 2025

    Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

    Papers in Europe PMC
  10. 10
    Gao JZ3 papers · 2025

    Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

1

interventional trials for this specific condition

1 interventional trial matched this specific condition name; none in our sample are currently recruiting.

Data as of 11 September 2026 · last trial check 28 July 2026

1 interventional trial — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 80.1th percentile).

low confidence · 80.1th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

1 interventional trials matched after quoted-phrase search and title/condition post-filter.

No currently recruiting studies in the matched set. Open the same 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 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · 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).

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 Periodic fever-infantile enterocolitis-autoinflammatory syndrome — 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.

("Periodic fever-infantile enterocolitis-autoinflammatory syndrome" OR "NLRC4-related autoinflammatory syndrome with macrophage activation syndrome" OR "NLRC4-related infantile enterocolitis-autoinflammatory syndrome" OR "NLRC4-related macrophage activation syndrome" OR "NLRC4-related MAS" OR "NLRC4-related autoinflammatory syndrome with MAS" OR "Autoinflammation with Infantile Enterocolitis") OR ("NLRC4" OR "NLRC4 syndrome" OR "NLRC4-related")

Run this search on Europe PMC

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

"Periodic fever-infantile enterocolitis-autoinflammatory syndrome" OR "NLRC4-related autoinflammatory syndrome with macrophage activation syndrome" OR "NLRC4-related infantile enterocolitis-autoinflammatory syndrome" OR "NLRC4-related macrophage activation syndrome" OR "NLRC4-related MAS" OR "NLRC4-related autoinflammatory syndrome with MAS" OR "Autoinflammation with Infantile Enterocolitis"

Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).

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

Query health: ok — strategies attempted: phrase; with hits: phrase

Run this search on ClinicalTrials.gov

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (9075) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T16:09:21.364Z