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ORPHA:35878

Hyperinsulinism-hyperammonemia syndrome

low confidenceDisorder

Also known as: HI/HA syndrome

Publications

3,472

Trials

2

Interventional, condition-specific

Researchers

1,020

Distinct authors in sample

Gene link

GLUD1

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare diffuse form of hyperinsulinism characterized by an excessive/ uncontrolled insulin secretion (inappropriate for the level of glycemia), chronic and recurrent episodes of induced by fasting and protein rich meals. and cognitive deficit, which are unrelated to but possibly related to the chronic , may also occur. This disorder is usually responsive to diazoxide treatment.

How rare: How common this is has not been clearly measured.

Orphanet entry

Cross-references

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

Additional Mondo synonyms (7)

GDH hyperinsulinism · GLUD1 hyperinsulinism · glutamate dehydrogenase 1 hyperinsulinism · hi/HA syndrome · hyperinsulinemic hypoglycemia, familial, type 6 · hyperinsulinism-hyperammonemia syndrome · hyperinsulinism/hyperammonemia syndrome

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 — GLUD1

  2. LiteraturePresent

    3,472 matched papers (2,620 in last 10 years) Source

  3. Phenotype characterisedPresent

    19 HPO annotations (e.g. Hypoglycemic seizures; Abnormality of the pancreatic islet cells; Hypoglycemic coma) 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

    2 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 (GLUD1).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

19

Associated phenotypes · MONDO:0011717

  • Hypoglycemic seizures
  • Abnormality of the pancreatic islet cells
  • Hypoglycemic coma
  • Asymptomatic hyperammonemia
  • Failure to thrive

Showing 5 of 19 — 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

1

Drugs / clinical candidates · MONDO_0011717

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

3,472

3,472 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.

3,472 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).

2,620 in the last 10 years · low confidence

Phrase hits: 220 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,020

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
    Stanley CA21 papers · 2025

    Division of Endocrinology, The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104.

    Papers in Europe PMC
  2. 02
    Hussain K13 papers · 2019

    Great Ormond Street Hospital for Children, UCL Institute of Child Health, Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme, London, UK Phone: +44 2079052128 E-mail: khalid.hussain@ucl.ac.uk.

    Papers in Europe PMC
  3. 03
    Smith TJ9 papers · 2019

    Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO 63132, USA. tsmith@danforthcenter.org

    Papers in Europe PMC
  4. 04
    Rosenfeld E8 papers · 2026

    Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

    Papers in Europe PMC
  5. 05
    De León DD7 papers · 2023

    Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

    Papers in Europe PMC
  6. 06
    Li C7 papers · 2019

    Division of Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.

    Papers in Europe PMC
  7. 07
    Hsu BY6 papers · 2006

    Division of Endocrinology, the Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

    Papers in Europe PMC
  8. 08
    Kelly A6 papers · 2006

    Division of Endocrinology, The Children's Hospital of Philadelphia, and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

    Papers in Europe PMC
  9. 09
    Boodhansingh KE5 papers · 2026

    Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

    Papers in Europe PMC
  10. 10
    Dionisi-Vici C5 papers · 2022

    Division of Metabolism, Bambino Gesù Children’s Research Hospital, Piazza S. Onofrio 4, Rome, 00165 Italy

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

2

interventional trials for this specific condition

2 interventional trials matched this specific condition name; none in our sample are currently recruiting.

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

2 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 84.5th percentile).

low confidence · 84.5th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

2 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.

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.

None of the matched observational studies is currently listed as 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 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · dropped 0 · fetched 2026-07-29

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 Hyperinsulinism-hyperammonemia syndrome — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

Likely covered — the policy lists Congenital hyperinsulinism as a category (Group 1), and this condition is a form of it. Confirm eligibility with a Centre of Excellence.

Group 1 — one-time curative treatment

Up to ₹50 lakh per patient

Financial support for treatment at notified Centres of Excellence (figures evolved from the original ₹20 lakh Group-1 ceiling).

Policy figures change. Verify current MoHFW / CoE guidance before relying on any amount. Verify

Centres of Excellence (15)
  • All India Institute of Medical Sciences (AIIMS) — New Delhi, Delhi
  • Maulana Azad Medical College — New Delhi, Delhi
  • Sanjay Gandhi Post Graduate Institute of Medical Sciences — Lucknow, Uttar Pradesh
  • Post Graduate Institute of Medical Education and Research (PGIMER) — Chandigarh, Chandigarh
  • Centre for DNA Fingerprinting & Diagnostics with Nizam’s Institute of Medical Sciences — Hyderabad, Telangana
  • King Edward Memorial Hospital — Mumbai, Maharashtra
  • Institute of Post-Graduate Medical Education and Research (IPGMER) — Kolkata, West Bengal
  • Centre for Human Genetics with Indira Gandhi Hospital — Bengaluru, Karnataka
  • Institute of Child Health and Hospital for Children (ICH & HC) — Chennai, Tamil Nadu
  • All India Institute of Medical Sciences (AIIMS) — Jodhpur, Rajasthan
  • Sree Avittam Thirunal Hospital (SAT), Government Medical College — Thiruvananthapuram, Kerala
  • All India Institute of Medical Sciences (AIIMS) — Bhopal, Madhya Pradesh
  • Regional Institute of Medical Sciences (RIMS) — Imphal, Manipur
  • All India Institute of Medical Sciences (AIIMS) — Patna, Bihar
  • Assam Medical College & Hospital — Dibrugarh, Assam

Voluntary contributions / crowdfunding (separate from CoE funding): https://rarediseases.mohfw.gov.in/

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.

("Hyperinsulinism-hyperammonemia syndrome" OR "HI/HA syndrome" OR "GDH hyperinsulinism" OR "GLUD1 hyperinsulinism" OR "glutamate dehydrogenase 1 hyperinsulinism" OR "hyperinsulinemic hypoglycemia, familial, type 6" OR "hyperinsulinism/hyperammonemia syndrome") OR ("GLUD1" OR "GLUD1 syndrome" OR "GLUD1-related")

Run this search on Europe PMC

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

"Hyperinsulinism-hyperammonemia syndrome" OR "HI/HA syndrome" OR "GDH hyperinsulinism" OR "GLUD1 hyperinsulinism" OR "glutamate dehydrogenase 1 hyperinsulinism" OR "hyperinsulinemic hypoglycemia, familial, type 6" OR "hyperinsulinism/hyperammonemia syndrome"

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: 2 interventional · 1 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 (3472) is extremely high with unknown/missing prevalence — treat as possible over-matching, not proven research intensity

Ingested 2026-07-26T23:50:07.470Z