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ORPHA:512

Metachromatic leukodystrophy

medium confidenceDisorder

Also known as: Arylsulfatase A deficiency · MLD

Publications

11,743

95.7th percentile

Trials

23

Interventional, condition-specific

Researchers

1,336

Distinct authors in sample

Gene link

ARSA

Definitive

Readiness

6/6

Stages with a signal

Clinical definition (Orphanet)

A rare lysosomal disease characterized by accumulation of sulfatides in the central and peripheral nervous system due to deficiency of the arylsulfatase A, leading to demyelination. Three clinical subtypes can be distinguished based on the age of onset: late , juvenile, and adult. Lead symptoms are deterioration in motor or cognitive function or behavioral problems, depending on the subtype, all eventually culminating in a decerebrated state and death after a highly variable disease course and duration. Mode of inheritance is .

How rare: 1-9 / 100 000 — about one to nine people per hundred thousand.

Orphanet entry

Cross-references

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

Additional Mondo synonyms (1)

arylsulfatase A deficiency

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.”

6/6 stages with a signal

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

  1. Gene identifiedPresent

    Definitive — ARSA

  2. LiteraturePresent

    11,743 matched papers (6,343 in last 10 years) Source

  3. Phenotype characterisedPresent

    222 HPO annotations (e.g. Motor deterioration; Dysphagia; Hyporeflexia) Source

  4. Animal modelPresent

    3 genotype models (Mus musculus) Source

  5. Orphan designationPartial

    4 EMA designations (none yet with FDA orphan-indication approval) — e.g. recombinant human arylsulfatase A Source

  6. Interventional trialPresent

    23 matched on ClinicalTrials.gov (2 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 (ARSA).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

222

Associated phenotypes · MONDO:0018868

  • Motor deterioration
  • Dysphagia
  • Hyporeflexia
  • Gait disturbance
  • Frequent falls

Showing 5 of 222 — open Monarch for the full list.

Animal models (Monarch / Alliance)

3

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)

4

Designations · no FDA orphan-indication approval yet

  • EMA recombinant human arylsulfatase Atreatment of metachromatic leukodystrophy · 26/11/2010 · PositiveEMA designation
  • EMA autologous CD34+ cells transfected with lentiviral vector containing the human arylsulfatase A cDNA (Libmeldy)treatment of metachromatic leukodystrophy · 13/04/2007 · PositiveEMA designation
  • EMA adeno-associated virus serotype HSC15 expressing human arylsulfatase A genetreatment of metachromatic leukodystrophy · 26/06/2020 · WithdrawnEMA designation
  • EMA recombinant human arylsulfatase Atreatment of metachromatic leukodystrophy · 09/07/2003 · WithdrawnEMA designation

Sources: FDA OOPD · EMA orphan designations

Open Targets candidates

8

Drugs / clinical candidates · MONDO_0018868

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

11,743

11,743 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.

11,743 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).

6,343 in the last 10 years · medium confidence · 95.7th percentile (publications denominator)

Phrase hits: 4,027 · 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
    Groeschel S17 papers · 2026

    Department of Neuropediatrics, Developmental Neurology and Social Pediatrics University of Tuebingen Tuebingen Germany.

    Papers in Europe PMC
  2. 02
    Wolf NI17 papers · 2026

    Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Cellular & Molecular Mechanisms, Vrije Universiteit, Amsterdam, Netherlands.

    Papers in Europe PMC
  3. 03
    Adang LA13 papers · 2026

    Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address: adangl@chop.edu.

    Papers in Europe PMC
  4. 04
    Fumagalli F12 papers · 2026

    Ospedale San Raffaele, Via Olgettina 60, Milano 20132, Italy. Electronic address: fumagalli.francesca@hsr.it.

    Papers in Europe PMC
  5. 05
    Laugwitz L12 papers · 2026

    Department of Neuropediatrics, Developmental Neurology and Social Pediatrics University of Tuebingen Tuebingen Germany.

    Papers in Europe PMC
  6. 06
    van der Knaap MS12 papers · 2026

    Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Cellular & Molecular Mechanisms, Vrije Universiteit, Amsterdam, Netherlands.

    Papers in Europe PMC
  7. 07
    Sevin C10 papers · 2026

    Reference Center for Leukodystrophies, Pediatric Neurology Department, Hôpital Bicêtre, Le Kremlin Bicêtre, France.

    Papers in Europe PMC
  8. 08
    Calbi V9 papers · 2026

    San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Pediatric Immunohematology Unit and Neurology and Neurophysiology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.

    Papers in Europe PMC
  9. 09
    Sevagamoorthy A9 papers · 2026

    Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

    Papers in Europe PMC
  10. 10
    Vanderver A9 papers · 2026

    Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

23

interventional trials for this specific condition

23 interventional trials matched this specific condition name; 2 currently recruiting in our sample. 8 trials are registered for leukodystrophy, the broader category — shown separately because they may or may not enrol this specific subtype.

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

23 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 95.3th percentile).

medium confidence · 95.3th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

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

Broader category: leukodystrophy

8

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

12 observational studies match 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

General rare disease registries you may be eligible for

These studies enroll across many rare conditions. They are not counted as evidence that anyone is studying this specific disease.

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 7 · after dedupe 7 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 7 · 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).

Uncertain / not reviewed (7)

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 Metachromatic leukodystrophy — 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.

("Metachromatic leukodystrophy" OR "Arylsulfatase A deficiency") OR ("ARSA" OR "ARSA syndrome" OR "ARSA-related")

Run this search on Europe PMC

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

"Metachromatic leukodystrophy" OR "Arylsulfatase A deficiency"

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: 23 interventional · 12 observational · 3 expanded access. Only interventional studies enter the trial headline.

Parent-category trials query:

"leukodystrophy"

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

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: MLD

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

Ingested 2026-07-26T14:07:44.793Z