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ORPHA:436

Hypophosphatasia

low confidenceDisorder

Also known as: HPP · Phosphoethanolaminuria · Rathbun disease

Publications

11,378

Trials

20

Interventional, condition-specific

Researchers

961

Distinct authors in sample

Gene link

ALPL

Definitive

Readiness

6/6

Stages with a signal

Clinical definition (Orphanet)

A rare, genetic disorder characterized by reduced activity of unfractionated serum alkaline phosphatase (ALP) and various symptoms from life-threatening, severely impaired mineralization at birth to musculo-skeletal pain in adulthood.

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 (3)

Rathburn disease · deficiency of alkaline phosphatase (disorder) [ambiguous] · phosphoethanolaminuria

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 — ALPL

  2. LiteraturePresent

    11,378 matched papers (7,807 in last 10 years) Source

  3. Phenotype characterisedPresent

    91 HPO annotations (e.g. Abnormality of the dentition; Seizure; Hypercalcemia) Source

  4. Animal modelPresent

    14 genotype models (Mus musculus, Danio rerio) Source

  5. Orphan designationPartial

    1 FDA · 2 EMA designations (none yet with FDA orphan-indication approval) — e.g. recombinant human alkaline phosphatase Source

  6. Interventional trialPresent

    20 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 (ALPL).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

91

Associated phenotypes · MONDO:0018570

  • Abnormality of the dentition
  • Seizure
  • Hypercalcemia
  • Failure to thrive
  • Anemia

Showing 5 of 91 — open Monarch for the full list.

Animal models (Monarch / Alliance)

14

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)

3

Designations · no FDA orphan-indication approval yet

  • EMA recombinant human alkaline phosphataseTreatment of hypophosphatasia · 15/01/2015 · PositiveEMA designation
  • EMA recombinant human tissue non-specific alkaline phosphatase - Fc - deca-aspartate fusion protein (Strensiq)Treatment of hypophosphatasia · 04/12/2008 · PositiveEMA designation
  • FDA Asfotase alfa (Strensiq)Hypophosphatasia · 2008-09-12

Sources: FDA OOPD · EMA orphan designations

Open Targets candidates

11

Drugs / clinical candidates · MONDO_0018570

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

11,378

11,378 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.

11,378 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).

7,807 in the last 10 years · low confidence

Phrase hits: 3,642 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

961

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
    Brandi ML7 papers · 2026

    F.I.R.M.O. Italian Foundation for the Research on Bone Diseases, Florence, Italy.

    Papers in Europe PMC
  2. 02
    Ozono K7 papers · 2026

    Department of Pediatrics, Graduate School of Medicine, The University of Osaka, Osaka, Japan. keioz@ped.med.osaka-u.ac.jp.

    Papers in Europe PMC
  3. 03
    Seefried L7 papers · 2026

    Osteology and Clinical Trial Unit, König-Ludwig-Haus, University of Würzburg, Würzburg, Germany. lothar.seefried@uni-wuerzburg.de.

    Papers in Europe PMC
  4. 04
    Dahir KM6 papers · 2026

    Vanderbilt University Medical Center, Nashville, Tennessee, USA.

    Papers in Europe PMC
  5. 05
    Högler W6 papers · 2026

    Johannes Kepler University Linz, Linz, Austria.

    Papers in Europe PMC
  6. 06
    Rush ET6 papers · 2026

    Children's Mercy Kansas City, Kansas City, MO, USA.

    Papers in Europe PMC
  7. 07
    Fang S5 papers · 2026

    Alexion, AstraZeneca Rare Disease, Boston, MA, USA.

    Papers in Europe PMC
  8. 08
    Kishnani PS5 papers · 2026

    Duke University Hospital, Durham, North Carolina, USA priya.kishnani@duke.edu.

    Papers in Europe PMC
  9. 09
    Foster BL4 papers · 2026

    Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH 43210, United States.

    Papers in Europe PMC
  10. 10
    Martos-Moreno GÁ4 papers · 2026

    Hospital Infantil Universitario Niño Jesús, IIS La Princesa, Universidad Autónoma de Madrid, CIBERobn, ISCIII, Madrid, Spain.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

20

interventional trials for this specific condition

20 interventional trials matched this specific condition name; 1 currently recruiting in our sample.

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

20 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 94.8th percentile).

low confidence · 94.8th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

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

Observational and natural-history studies

23 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 6 · after dedupe 5 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 5 · 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 (5)

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 Hypophosphatasia — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

Directly listed under NPRD Group 3.

Group 3 — high-cost / lifelong therapy with careful selection

Up to ₹50 lakh per patient

Financial support at notified Centres of Excellence is the figure commonly cited in recent MoHFW/PIB statements. Many Group 3 patients also use the MoHFW voluntary-contribution / crowdfunding portal.

Eligibility and patient selection rules change. Verify with a CoE; the crowdfunding portal is a separate mechanism from CoE funding. 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.

("Hypophosphatasia" OR "Phosphoethanolaminuria" OR "Rathbun disease" OR "Rathburn disease" OR "deficiency of alkaline phosphatase (disorder) [ambiguous]" OR "deficiency of the alkaline phosphatase (disorder) [ambiguous]") OR ("ALPL" OR "ALPL syndrome" OR "ALPL-related")

Run this search on Europe PMC

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

"Hypophosphatasia" OR "Phosphoethanolaminuria" OR "Rathbun disease" OR "Rathburn disease" OR "deficiency of alkaline phosphatase (disorder) [ambiguous]" OR "deficiency of the alkaline phosphatase (disorder) [ambiguous]"

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: 20 interventional · 23 observational · 1 expanded access. Only interventional studies enter the trial headline.

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

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: HPP

Confidence reasoning

  • Preferred label is short or not clearly distinctive
  • 1 synonym(s) dropped by stoplist (may under-count)
  • No label/synonym collisions with other diseases in this corpus

Ingested 2026-07-26T13:50:09.481Z