ORPHA:356978
D,L-2-hydroxyglutaric aciduria
Also known as: D,L-2-hydroxyglutaric acidemia · Combined D-2-hydroxyglutaric acidemia and L-2-hydroxyglutaric acidemia · Combined D-2-hydroxyglutaric aciduria and L-2-hydroxyglutaric aciduria · D,L-2-HGA
Publications
1,613
Trials
1
Interventional, condition-specific
Researchers
260
Distinct authors in sample
Gene link
SLC25A1
Definitive
Readiness
4/6
Stages with a signal
Clinical definition (Orphanet)
A rare inborn error of metabolism characterized by severe epileptic , episodes of apnea and respiratory distress, severe global or absent psychomotor development, severe muscular or absent voluntary movements, feeding difficulties and , absence of visual contact, abnormal brain morphology (including cerebral atrophy, ventriculomegaly and hypoplasia or of the corpus callosum), mild features (frontal bossing, hypertelorism, downslanting palpebral fissures, flat nasal bridge), elevated CSF and plasma lactate and urinary Krebs cycle metabolites.
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.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0014072
- OMIM:615182
- UMLS:C5574940
Additional Mondo synonyms (2)
combined D-2-hydroxyglutaric acidemia and L-2-hydroxyglutaric acidemia · combined D-2-hydroxyglutaric aciduria and L-2-hydroxyglutaric aciduria
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.
- Gene identifiedPresent
Definitive — SLC25A1
- LiteraturePresent
1,613 matched papers (1,321 in last 10 years) Source
- Phenotype characterisedPresent
23 HPO annotations (e.g. Encephalopathy; Feeding difficulties; Elevated CSF L-2-hydroxyglutaric acid concentration) Source
- Animal modelNot found
No Alliance genotype “model of” associations via Monarch for these Mondo IDs
- Orphan designationNot found
No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source
- Interventional trialPresent
1 matched on ClinicalTrials.gov (1 recruiting in sample)
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 (SLC25A1).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
23
Associated phenotypes · MONDO:0014072
- Encephalopathy
- Feeding difficulties
- Elevated CSF L-2-hydroxyglutaric acid concentration
- Irritability
- Microcephaly
Showing 5 of 23 — 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.
CTD chemicals (MyDisease.info)
No CTD chemical associations returned for this Mondo ID.
Literature
Is anyone studying this?
1,613
1,613 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.
1,613 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).
1,321 in the last 10 years · low confidence
Phrase hits: 42 · MeSH hits: 0
Who's working on it?
260
Distinct author names in 42 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.
- 01Salomons GS6 papers · 2019
Metabolic Unit, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
Papers in Europe PMC - 02Struys EA6 papers · 2018
Metabolic Unit, Department of Clinical Chemistry, VU Medical Center, Amsterdam, The Netherlands. e.struys@vumc.nl
Papers in Europe PMC - 03Jakobs C5 papers · 2013Papers in Europe PMC
- 04Avantaggiati ML4 papers · 2025
Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, USA.
Papers in Europe PMC - 05Vockley J4 papers · 2025
Department of Pediatrics, Division of Genetic and Genomic Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Papers in Europe PMC - 06Kasprzyk-Pawelec A3 papers · 2025
Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, USA.
Papers in Europe PMC - 07Santer R3 papers · 2018
Department of Pediatrics, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
Papers in Europe PMC - 08Van der Knaap MS3 papers · 2014Papers in Europe PMC
- 09Albanese C2 papers · 2025
Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, D.C., USA.
Papers in Europe PMC - 10Dobrowolski SF2 papers · 2024
Department of Pathology, Clinical Biochemical Genetics Laboratory, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, 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; 1 currently recruiting in our sample.
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.
- NCT07125066·ENROLLING BY INVITATION·An Individual Patient, Open Label Study to Use ACER-001 to Treat Combined D,L-2 Hydroxyglutaric Aciduria (C-2HGA)
Not reviewed·Conditions: Combined D,L-2-hydroxyglutaric Aciduria·Matched via name phrase
Broader category: 2-hydroxyglutaric aciduria
0
Interventional trials for the parent category, exclusive of NCT IDs already counted above. Eligibility for this subtype is not guaranteed.
Parent-category matching found a broader label but no interventional trials under it. How we count trials.
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 60 · after dedupe 60 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 60 · 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 (60)
- ctis·2025-523650-14-00·Authorised·functional imaging of digital osteoarthritis and rheumatoid arthritis using 99mTc-NTP15-5 in nuclear medicine : phase II clinical study
skipped — LLM skipped (--skip-llm)
- ctis·2026-525417-31-00·Authorised·A randomised active-controlled trial to assess the safety and pharmacodynamics of two blinded doses of vortosiran and open-label apixaban in patients with non-valvular atrial fibrillation
skipped — LLM skipped (--skip-llm)
- ctis·2025-523994-41-00·Authorised·A Phase III, Randomized, Double-blind, Parallel-group, Placebo-controlled Multicenter Study to Evaluate the Effect of Elecoglipron in Reducing Renal Outcomes and Mortality in Participants with Chronic Kidney Disease (Elevate-CKD)
skipped — LLM skipped (--skip-llm)
- ctis·2026-525185-21-00·Authorised·IKF-099/D-FLOT-TNT
Total Neoadjuvant Treatment with preoperative FLOT/Durvalumab plus postoperative Durvalumab for Resectable Gastroesophageal Adenocarcinoma
skipped — LLM skipped (--skip-llm)
- ctis·2025-523435-18-00·Authorised·Colchicine for the Reduction of Dependency and Vascular Events after an Acute Intracerebral Hemorrhage (CoVasc-ICH2)
skipped — LLM skipped (--skip-llm)
- ctis·2026-525620-23-00·Authorised·Local and systemic immune modulation by Rilvegostomig (AZD2936) in the treatment of advanced gastric cancer (RILVE Project)
skipped — LLM skipped (--skip-llm)
- ctis·2025-524359-30-00·Authorised·Tarlatamab Before and After Surgery for Recurrent High-Grade Glioma
skipped — LLM skipped (--skip-llm)
- ctis·2025-524249-29-00·Authorised·A placebo-controlled comparability study to compare two presentations of cagrilintide for weight management in participants with overweight or obesity
skipped — LLM skipped (--skip-llm)
- ctis·2026-525917-29-00·Authorised, recruiting·Early TRIPLE versus dual LIPID lowering treatment in peOple with atherosclerotic cardiovascular disease and hypercholesterolemia Undergoing elecTive revascularisation -
The randomized, controlled, open-label, parallel group TRIPLE-LIPID-OUT trial
skipped — LLM skipped (--skip-llm)
- ctis·2025-524442-10-00·Authorised·Achieving viral CLEARance in immunocompromised participants with long-term persistence of SARS-CoV-2 - an open-label randomized trial (CLEAR)
skipped — LLM skipped (--skip-llm)
- ctis·2025-523092-33-00·Authorised·Effect of Vitamin D supplementation on MyocardIal Fibrosis in PaTients with Acute Myocarditis (EDIT-AM): a multicenter, open-label, randomized controlled trial
skipped — LLM skipped (--skip-llm)
- ctis·2025-523923-22-00·Authorised·A Phase 2, Open-Label, Single-Arm Study of Lirafugratinib in Patients With Previously Treated, Unresectable, Locally Advanced or Metastatic Solid Tumors (Excluding Cholangiocarcinoma) With FGFR2 Fusion or Rearrangement
skipped — LLM skipped (--skip-llm)
- ctis·2025-524213-84-00·Authorised·TAILORswitch (PADA-2): rising ctDNA to tailor endocrine therapy switch in patients with ER+/HER2- metastatic breast cancer
skipped — LLM skipped (--skip-llm)
- ctis·2026-525421-20-00·Authorised·An open label, balanced, randomized, single dose, two-treatment, two period, two-sequence, crossover, bioequivalence study comparing Fexofenadine HCl and Pseudoephedrine HCl Extended Release Tablet 180 mg/240 mg, Manufactured by: Sun Pharmaceutical Industries Limited, India with Allegra-D® 24 HR (Fexofenadine HCl and Pseudoephedrine HCl Extended Release Tablets 180 mg + 240 mg) tablets, Distributed by: Chattem Inc., a Sanofi Company Chattanooga, TN 37409-0219, USA, in healthy, adult, human participants under fed conditions.
skipped — LLM skipped (--skip-llm)
- ctis·2026-525420-22-00·Authorised·An open label, balanced, randomized, single dose, two-treatment, four period, two-sequence, crossover, fully replicate, bioequivalence study comparing Fexofenadine Hydrochloride and Pseudoephedrine Hydrochloride Extended Release Tablet USP 180 mg/240 mg, Manufactured by: Sun Pharmaceutical Industries Limited, India with Allegra-D® 24 HR (Fexofenadine HCl and Pseudoephedrine HCl Extended Release Tablets 180 mg + 240 mg) tablets, Distributed by: Chattem Inc., a Sanofi Company Chattanooga, TN 37409-0219, USA, in healthy, adult, human participants under fasting conditions.
skipped — LLM skipped (--skip-llm)
- ctis·2026-526314-90-00·Authorised·Unprescribing the Pill to Reassess Symptom and Cognitive Recovery in Depression (UNPRESCRIB-D)
skipped — LLM skipped (--skip-llm)
- ctis·2026-526167-38-00·Authorised·ALBUMINUS: Dose reduction of human albumin during large-volume paracentesis in patients with cirrhosis
skipped — LLM skipped (--skip-llm)
- ctis·2025-524976-40-00·Authorised·ECSIP : Early Corticosteroids in Severe Influenza Pneumonia, a phase III randomized controlled trial
skipped — LLM skipped (--skip-llm)
- ctis·2025-524048-36-00·Authorised·Paclitaxel plus ramucirumab and tislelizumab as switch maintenance versus continuation of chemotherapy and tislelizumab in patients with advanced HER2-negative and PD-L1 positive gastroesophageal adenocarcinoma: the ARMANI-2/ENGIC08 trial by GONO
skipped — LLM skipped (--skip-llm)
- ctis·2026-525643-32-00·Authorised·STOP - Safety and efficacy of a STOPping strategy versus classical maintenance dose of JAK inhibitors in deep remission patients with ulcerative colitis: a randomized controlled trial
skipped — LLM skipped (--skip-llm)
- ctis·2025-524487-37-00·Authorised, recruiting·Real-World Effectiveness and Safety of Pegcetacoplan in Patients with C3 Glomerulopathy (C3G) or Primary Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN): A Multi-Country Study (PRISMC3)
skipped — LLM skipped (--skip-llm)
- ctis·2025-524728-22-01·Authorised·ACTIVATE - Phase 1 Clinical Trial evaluating the combination of Actinomycin D and venetoclax in patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
skipped — LLM skipped (--skip-llm)
- ctis·2025-523990-40-00·Authorised·Accelerate Improvement in Multiple Myeloma for Newly Diagnosed Transplant-Eligible Patients (AugMMent)
skipped — LLM skipped (--skip-llm)
- ctis·2025-523432-39-01·Authorised·A Phase 1/2, Open-label Study of VS-7375, a KRAS G12D (ON/OFF) Inhibitor, as Monotherapy and in Combination, in Patients with Advanced KRAS G12D-Mutant Solid Tumors
skipped — LLM skipped (--skip-llm)
- ctis·2025-523397-16-00·Authorised·Phase IIb Multicenter Randomized Controlled Trial Evaluating the Efficacy of Sivelestat in Patients with Septic Coagulopathy
skipped — LLM skipped (--skip-llm)
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 D,L-2-hydroxyglutaric aciduria — check Associations / patient organisations on that page.
India — NPRD
Last verified 2026-07-26This 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.
("D,L-2-hydroxyglutaric aciduria" OR "D,L-2-hydroxyglutaric acidemia" OR "Combined D-2-hydroxyglutaric acidemia and L-2-hydroxyglutaric acidemia" OR "Combined D-2-hydroxyglutaric aciduria and L-2-hydroxyglutaric aciduria" OR "D,L-2-HGA") OR ("SLC25A1" OR "SLC25A1 syndrome" OR "SLC25A1-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"D,L-2-hydroxyglutaric aciduria" OR "D,L-2-hydroxyglutaric acidemia" OR "Combined D-2-hydroxyglutaric acidemia and L-2-hydroxyglutaric acidemia" OR "Combined D-2-hydroxyglutaric aciduria and L-2-hydroxyglutaric aciduria" OR "D,L-2-HGA"
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.
Parent-category trials query:
"2-hydroxyglutaric aciduria"
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 (1613) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity
Ingested 2026-07-27T14:28:24.463Z