RARE DISEASERESEARCH ATLAS
Open navigation menu

ORPHA:289504

Combined malonic and methylmalonic acidemia

high confidenceDisorder

Also known as: CMAMMA · Combined malonic and methylmalonic aciduria

Publications

563

83th percentile

Trials

0

Interventional, condition-specific

Researchers

1,009

Distinct authors in sample

Gene link

ACSF3

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare inborn error of metabolism characterized by elevation of malonic acid (MA) and methylmalonic acid (MMA) in body fluids, with higher levels of MMA than MA. CMAMMA presents in childhood with , , dystonia and or in adulthood with , memory loss and cognitive decline.

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 (2)

combined malonic and methylmalonic acidemia · combined malonic and methylmalonic 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

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

  1. Gene identifiedPresent

    Definitive — ACSF3

  2. LiteraturePresent

    563 matched papers (482 in last 10 years) Source

  3. Phenotype characterisedPresent

    34 HPO annotations (e.g. Global developmental delay; Methylmalonic aciduria; Diarrhea) 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 trialPartial

    None under the specific name; 15 for broader category methylmalonic acidemia

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 (ACSF3).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

34

Associated phenotypes · MONDO:0013661

  • Global developmental delay
  • Methylmalonic aciduria
  • Diarrhea
  • Ketoacidosis
  • Vomiting

Showing 5 of 34 — 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?

563

563 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.

563 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).

482 in the last 10 years · high confidence · 83th percentile (publications denominator)

Phrase hits: 125 · MeSH hits: 2

Open Europe PMC search

Who's working on it?

1,009

Distinct author names in 125 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
    Venditti CP7 papers · 2022

    Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. venditti@mail.nih.gov.

    Papers in Europe PMC
  2. 02
    Sloan JL5 papers · 2022

    Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

    Papers in Europe PMC
  3. 03
    Tucci S5 papers · 2026

    Department of General Pediatrics, Center for Pediatrics and Adolescent Medicine, Faculty of Medicine and Medical Centre, University of Freiburg, 79106 Freiburg, Germany. Electronic address: sara.tucci@uniklinik-freiburg.de.

    Papers in Europe PMC
  4. 04
    Wajner M5 papers · 2025

    Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal de Rio Grande do Sul, Porto Alegre, RS, Brazil.

    Papers in Europe PMC
  5. 05
    Manoli I4 papers · 2022

    Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

    Papers in Europe PMC
  6. 06
    Biesecker LG3 papers · 2023

    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. lesb@mail.nih.gov

    Papers in Europe PMC
  7. 07
    Engelke UFH3 papers · 2023

    Department of Laboratory Medicine, Translational Metabolic Laboratory (TML), Radboud University Medical Center, Nijmegen, The Netherlands.

    Papers in Europe PMC
  8. 08
    Guo B3 papers · 2026

    Department of Radiology, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

    Papers in Europe PMC
  9. 09
    Li C3 papers · 2026

    Informatics and Predictive Sciences, Research and Development, Bristol-Myers Squibb, Cambridge, MA, USA.

    Papers in Europe PMC
  10. 10
    Li J3 papers · 2025

    Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

    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. 15 trials are registered for methylmalonic acidemia, 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.

high 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.

15 interventional trials matched methylmalonic acidemia, the broader category — listed below. Those studies are not counted in the condition-specific total.

Broader category: methylmalonic acidemia

15

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.

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 2026-07-30

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 Combined malonic and methylmalonic acidemia — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

Likely covered — the policy lists Methylmalonic acidemia as a category (Group 2), and this condition is a form of it. Confirm eligibility with a Centre of Excellence.

Group 2 — long-term / lifelong lower-cost interventions

NPRD envisages State Government support for dietary formulae, hormones, and other lower-cost interventions. This is a different route from the central CoE ₹50 lakh pathway; ask your state health department and a CoE which channel applies.

Central CoE funding may also apply depending on current rules — confirm with a notified Centre of Excellence. Do not assume the ₹50 lakh ceiling covers Group 2 by default. 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.

("Combined malonic and methylmalonic acidemia" OR "CMAMMA" OR "Combined malonic and methylmalonic aciduria") OR (MESH:"Combined Malonic and Methylmalonic Aciduria") OR ("ACSF3" OR "ACSF3 syndrome" OR "ACSF3-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Combined Malonic and Methylmalonic Aciduria

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

"Combined malonic and methylmalonic acidemia" OR "CMAMMA" OR "Combined malonic and methylmalonic aciduria"

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

Parent-category trials query:

"methylmalonic acidemia"

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

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

Ingested 2026-07-27T12:14:34.203Z