Primary Angle-Closure Glaucoma

Categories: Eye diseases, Neuronal diseases

Aliases & Classifications for Primary Angle-Closure Glaucoma

MalaCards integrated aliases for Primary Angle-Closure Glaucoma:

Name: Primary Angle-Closure Glaucoma 12 54 15 71 32
Primary Angle Closure Glaucoma 12 17
Angle Closure Glaucoma 71


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Disease Ontology 12 DOID:1405
ICD9CM 34 365.2
SNOMED-CT 67 193544008
ICD10 32 H40.2
UMLS 71 C0017605 C0017606

Summaries for Primary Angle-Closure Glaucoma

Disease Ontology : 12 An angle-closure glaucoma characterized by closure of the anterior chamber angle by an intrinsic defect such that aqueous outflow is blocked and the intraocular pressure becomes inappropriately elevated leading to optic nerve damage and visual field loss. Primary angle-closure glaucoma has symptom progressive peripheral vision loss, decreased vision, and pain, redness, and headache in acute cases. Primary angle closure glaucoma can be caused by anatomically narrow angle, defects in the trabecular meshwork, and iris abnormalities. Primary angle-closure glaucoma has a strong genetic component.

MalaCards based summary : Primary Angle-Closure Glaucoma, also known as primary angle closure glaucoma, is related to acute closed-angle glaucoma and intraocular pressure quantitative trait locus, and has symptoms including progressive peripheral vision loss An important gene associated with Primary Angle-Closure Glaucoma is MYOC (Myocilin), and among its related pathways/superpathways is Tropisetron Pathway, Pharmacokinetics/Pharmacodynamics. The drugs Pilocarpine and Travoprost have been mentioned in the context of this disorder. Affiliated tissues include eye, endothelial and retina, and related phenotypes are Resistant to vaccinia virus (VACV-A4L) infection and immune system

Related Diseases for Primary Angle-Closure Glaucoma

Diseases related to Primary Angle-Closure Glaucoma via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 92)
# Related Disease Score Top Affiliating Genes
1 acute closed-angle glaucoma 32.2 OPTN MYOC CYP1B1 CALCRL
2 intraocular pressure quantitative trait locus 32.0 OPTN MYOC CYP1B1
3 corneal edema 30.7 MYOC KERA CYP1B1
4 optic nerve disease 30.7 PARL OPTN MYOC
5 myopia 30.6 PRSS56 MYOC MMP9 COL11A1
6 glaucoma, primary open angle 30.6 TXNRD2 PLEKHA7 PCMTD1 OPTN MYOC MMP9
7 open-angle glaucoma 30.2 TXNRD2 OPTN MYOC MTHFR MMP9 CYP1B1
8 nanophthalmos 30.2 PRSS56 PLEKHA7 MYOC KERA
9 cycloplegia 30.1 PRSS56 KERA
10 amaurosis fugax 30.1 MTHFR MMP9
11 anterior segment dysgenesis 29.9 MYOC KERA CYP1B1
12 chronic closed-angle glaucoma 11.5
13 interval angle-closure glaucoma 11.4
14 glaucoma, primary closed-angle 11.4
15 cataract 11.0
16 yemenite deaf-blind hypopigmentation syndrome 10.9
17 refractive error 10.6
18 ocular hypertension 10.5
19 multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly 10.3
20 retinitis pigmentosa 10.3
21 neuroretinitis 10.3
22 microphthalmia 10.3
23 retinitis 10.3
24 neuropathy 10.3
25 traumatic glaucoma 10.3 MYOC CYP1B1
26 early-onset glaucoma 10.3 MYOC CYP1B1
27 excessive tearing 10.3 MYOC CYP1B1
28 mycetoma 10.3 MMP9 CYP1B1
29 microphthalmia, isolated 2 10.2 MYOC CYP1B1
30 retinal detachment 10.2
31 lens subluxation 10.2
32 uveitis 10.2
33 eye disease 10.2
34 scotoma 10.2
35 senile cataract 10.2
36 cytokine deficiency 10.2
37 farsightedness 10.2
38 pik3ca-related overgrowth syndrome 10.2
39 megalocornea 10.2 MYOC CYP1B1 COL11A1
40 hydrophthalmos 10.2 MYOC CYP1B1
41 steroid-induced glaucoma 10.1 MYOC CYP1B1
42 degenerative myopia 10.1 PRSS56 PARL
43 optic atrophy 1 10.1
44 cornea plana 2, autosomal recessive 10.1
45 leber hereditary optic neuropathy, modifier of 10.1
46 retinoschisis 1, x-linked, juvenile 10.1
47 astigmatism 10.1
48 anxiety 10.1
49 spastic paraplegia, intellectual disability, nystagmus, and obesity 10.1
50 familial adenomatous polyposis 10.1

Comorbidity relations with Primary Angle-Closure Glaucoma via Phenotypic Disease Network (PDN):

Hypertension, Essential

Graphical network of the top 20 diseases related to Primary Angle-Closure Glaucoma:

Diseases related to Primary Angle-Closure Glaucoma

Symptoms & Phenotypes for Primary Angle-Closure Glaucoma


  • progressive peripheral vision loss

GenomeRNAi Phenotypes related to Primary Angle-Closure Glaucoma according to GeneCards Suite gene sharing:

# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Resistant to vaccinia virus (VACV-A4L) infection GR00351-A-1 9.23 CALCRL COL11A1 GLIS3 HTR3C HTR3D KERA

MGI Mouse Phenotypes related to Primary Angle-Closure Glaucoma:

# Description MGI Source Accession Score Top Affiliating Genes
1 immune system MP:0005387 9.36 ABCC5 CALCRL COL11A1 DPM2 KERA MMP9

Drugs & Therapeutics for Primary Angle-Closure Glaucoma

Drugs for Primary Angle-Closure Glaucoma (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 37)
# Name Status Phase Clinical Trials Cas Number PubChem Id
Pilocarpine Approved, Investigational Phase 4 92-13-7, 54-71-7 5910
Travoprost Approved Phase 4 157283-68-6 5282226
Brinzolamide Approved Phase 4 138890-62-7 68844
4 Neurotransmitter Agents Phase 4
5 Muscarinic Agonists Phase 4
6 Cholinergic Agents Phase 4
7 Antihypertensive Agents Phase 4
8 Carbonic Anhydrase Inhibitors Phase 4
Timolol Approved Phase 3 26839-75-8 33624 5478
Latanoprost Approved, Investigational Phase 3 130209-82-4 5282380 5311221
11 Adrenergic Antagonists Phase 3
12 Anti-Arrhythmia Agents Phase 3
13 Adrenergic beta-Antagonists Phase 3
14 Adrenergic Agents Phase 3
15 Ophthalmic Solutions Phase 3
16 Adrenergic alpha-Agonists Phase 3
17 Brimonidine Tartrate Phase 3 70359-46-5
18 Adrenergic Agonists Phase 3
19 Pharmaceutical Solutions Phase 2
20 Prednisolone acetate Approved, Vet_approved 52-21-1
Prednisolone Approved, Vet_approved 50-24-8 5755
Prednisolone phosphate Approved, Vet_approved 302-25-0
Methylprednisolone hemisuccinate Approved 2921-57-5
Methylprednisolone Approved, Vet_approved 83-43-2 6741
Dipivefrin Approved 52365-63-6 3105
Bimatoprost Approved, Investigational 155206-00-1 5311027
Altretamine Approved 645-05-6 2123
Hyaluronic acid Approved, Vet_approved 9004-61-9 53477741
Mannitol Approved, Investigational 69-65-8 453 6251
Prednisolone hemisuccinate Experimental 2920-86-7
31 Methylprednisolone Acetate
32 Protective Agents
33 Viscosupplements
34 Immunologic Factors
35 Adjuvants, Immunologic
36 Anesthetics
37 Mitomycins

Interventional clinical trials:

(show all 38)
# Name Status NCT ID Phase Drugs
1 A Twelve-Week, Double Masked, Parallel Group, Primary-Therapy Pilot Study of the Safety and Efficacy of Travoprost 0.004% Compared to Pilocarpine 1% in Patients With Chronic Angle-Closure Glaucoma Completed NCT00762645 Phase 4 Travoprost 0.004% (Travatan);Pilocarpine 1%
2 A Double-Masked, Parallel-Group, Efficacy and Safety Study of Brinzolamide 1.0% (AZOPT) as Adjunctive Therapy to Travoprost 0.004% (TRAVATAN) in Patients With Chronic Angle-Closure Glaucoma Terminated NCT00758342 Phase 4 Travoprost 0.004% + Brinzolamide 1.0%;Travoprost 0.004% + Tears Natural
3 Comparison of Selective Laser Trabeculoplasty With Prostaglandin Analogues for Lowering Intraocular Pressure in Eyes With Primary Angle Closure Glaucoma Unknown status NCT01004900 Phase 3 Travoprost/ Timolol/ Azopt/ Brimonidine
4 Argon Laser Peripheral Iridoplasty for Primary Angle Closure Glaucoma: A Randomised Controlled Trial Unknown status NCT00980473 Phase 3 Travatan/ Timolol/Azopt
5 A Safety and Efficacy Study of Travoprost 0.004% Compared to Latanoprost 0.005% in Patients With Chronic Angle-Closure Glaucoma. Completed NCT00051181 Phase 3 Travoprost (0.004%);Latanoprost (0.005%)
6 A Prospective, Multicenter Clinical Trial Designed to Evaluate the Safety and Effectiveness of the XEN45 Glaucoma Treatment System in Patients With Angle Closure Glaucoma Recruiting NCT03362931 Phase 3
7 A Prospective Study to Assess the Hypotensive Efficacy of Rho-Kinase Inhibitor AR-12286 Ophthalmic Solution 0.5% and 0.7% in Patients With Chronic Angle-closure Glaucoma Unknown status NCT02152774 Phase 2 Rho-Kinase Inhibitor
8 Phase IIA Double-Masked Randomized Sham-Controlled Trial of QPI-1007 Delivered by a Single Intravitreal Injection to Subjects With Acute Primary Angle-Closure Glaucoma (APACG) Completed NCT01965106 Phase 2 QPI-1007 Injection;(including placebo)
9 Optical Coherence Tomography Quantitative Analysis of Changes in Anterior Chamber After Laser Peripheral Lridotomy Unknown status NCT02279472
10 Efficacy of Tafluprost as an Adjunct to Medical Therapy for Residual Primary Open Angle Glaucoma and Residual Primary Angle-closure Glaucoma After Trabeculectomy Unknown status NCT03595865 tafluprostin
11 Artificial Intelligence Screening on Patients With Primary Angle Closure Glaucoma Unknown status NCT03611387
12 Clinical Efficacy and Safety of Minimally Invasive Glaucoma Surgery on Chinese Primary Angle Closure Glaucoma Unknown status NCT02964676
13 Prospective Study on Ex-PRESS Implantation Combined With Phacoemulsification in Primary Angle-closure Glaucoma Unknown status NCT03323138
14 Anterior Segment Changes Before and After Uneventful Combined Phaco-Trabeculectomy by Using Optical Coherence Tomography (OCT) Unknown status NCT03626675
15 Prevalence of Chronic Angle Closure in Caucasian Hyperopic Subjects Unknown status NCT00823706
16 Comparison of Bimatoprost and Lataprost in Patients With Chronic Angle-Closure Glaucoma: A Randomized Cross-Over Study Unknown status NCT00567788 Latanoprost-Bimatoprost;Bimatoporost-Latanoprost
17 Laser Peripheral Iridotomy Induced Changes in Corneal Densitometry in Acute Primary Angle Closure Glaucoma Cases Completed NCT04254458
18 The Effect of Mozart Music on Visual Field Testing in Glaucoma Patients: Will Music Tame the Savage Perimeter? Completed NCT01027039
19 Prospective Evaluation of the Efficacy of Pascal Laser Iridotomy and Pascal Laser Peripheral Iridoplasty: A Pilot Study Completed NCT01020071
20 Comparison of Visante and Cirrus Optical Coherent Tomography for Assessment of the Anterior Segment Completed NCT01895686
21 Phacoemulsification Versus Phacoemulsification With Micro-bypass Stent Implantation in Primary Angle Closure and Primary Angle Closure Glaucoma: Randomized Double-masked Clinical Trial Completed NCT03647033
22 Angle Closure: Laser Iridotomy Versus Phacoemulsification Study (ACLIPS)- A Study of Acute Primary Angle Closure Glaucoma Comparing Two Treatment Modalities: Laser Peripheral vs Phacoemulsification With Posterior Intraocular Lens Implant Completed NCT00350428
23 Comparison of Combined Phacotrabeculectomy and Trabeculectomy Only in the Treatment of Primary Angle-closure Glaucoma Completed NCT01298635
24 A Randomised Comparative Study of the Effects of Cataract Extraction With Lens Implant Alone Versus Cataract Extraction With Lens Implant and Goniosynechialysis on Outflow Facility in Patients With Primary Angle Closure Glaucoma. Completed NCT00719290
25 Prevalence of Corneal Astigmatism Before Glaucoma Surgery in Chinese Patients With Primary Angle-closure Glaucoma Completed NCT03159780
26 A Prospective, Open Label Study Assessing the 24-hour Intraocular Pressure Pattern Monitored by SENSIMED Triggerfish® in Primary Angle Closure and Primary Angle Closure Glaucoma Patients, Before and After Laser Peripheral Iridotomy Completed NCT01906138
27 Sequential Laser Iridotomy Using Argon and Q-Switched 532 nm Frequency Doubled Neodymium Yag Laser: A Pilot Study Completed NCT00452998
28 Incidence of Visual Symptom Following Laser (Nd:YAG ) Peripheral Iridotomy (LPI) in Relation to Position of LPI Completed NCT01758237
29 Randomized Clinical Trial Comparing Neodynium:Ytrium-aluminium-garnet (Nd:YAG) Laser and Sequential Double Frequency YAG-Nd:YAG Laser Iridotomy in Patients With Dark Iris Completed NCT02474238
30 Short-term Outcomes of Iridoplasty for Persistent Angle Closure Despite Patent Iridotomies An Anterior Segment Optical Coherence Tomography Study Completed NCT02199158
31 Comparison of Anterior Chamber Paracentesis and Conventional Mannitol Infusion in Patients With Primary Acute Angle-closure Glaucoma Completed NCT01266343
32 A Novel Prophylactic Peripheral Iridectomy Prevents Aphakic Angle-closure Glaucoma After Congenital Cataract Surgery Completed NCT03610295
33 Hydrus Microstent and Lens Extraction for the Treatment of Primary Angle-Closure Glaucoma Recruiting NCT04622605
34 Phacoemulsification Combined With Trabeculectomy Versus Phacoemulsification Combined With Trabeculotomy for Treatment of Chronic Angle Closure Glaucoma Recruiting NCT04683055
35 Diagnostic Performance of Deep Convolutional Neural Networks for Angle Closre Glaucoma: an International Multicenter Study Recruiting NCT04242108
36 Investigating the Genetic Basis of Pseudoexfoliation Syndrome, Angle-closure Glaucoma and Primary Open-angle Glaucoma Recruiting NCT03423758
37 Effectiveness of Lens Extraction Combined With Goniosynechialysis Versus Trabeculectomy in Treating Advanced Angle-closure Glaucoma: a Randomized Controlled Trial Not yet recruiting NCT04703712
38 A Prospective, Open Label Study Assessing the 24-hour Intraocular Pressure Pattern Monitored by SENSIMED Triggerfish® in Primary Angle Closure and Primary Angle Closure Glaucoma Patients, Before and After Laser Peripheral Iridotomy Withdrawn NCT01906151

Search NIH Clinical Center for Primary Angle-Closure Glaucoma

Inferred drug relations via UMLS 71 / NDF-RT 51 :

demecarium bromide
Echothiophate Iodide
Pilocarpine Hydrochloride
Pilocarpine Nitrate

Genetic Tests for Primary Angle-Closure Glaucoma

Anatomical Context for Primary Angle-Closure Glaucoma

MalaCards organs/tissues related to Primary Angle-Closure Glaucoma:

Eye, Endothelial, Retina, Cortex, Neutrophil, Brain, Pituitary

Publications for Primary Angle-Closure Glaucoma

Articles related to Primary Angle-Closure Glaucoma:

(show top 50) (show all 1197)
# Title Authors PMID Year
[Two variants in MYOC and CYP1B1 genes in a Chinese family with primary angle-closure glaucoma]. 61 54
18841557 2008
Molecular analysis of the myocilin gene in Chinese subjects with chronic primary-angle closure glaucoma. 54 61
15790895 2005
The role of clinical examination of the optic nerve head in glaucoma today. 61
33470671 2021
Ultrasound cycloplasty in Chinese glaucoma patients: Results of a 6-month prospective clinical study. 61
33540418 2021
Glaucoma Expert-level Detection of Angle Closure in Goniophotographs with Convolutional Neural Networks: The Chinese American Eye Study: Automated Angle Closure Detection in Goniophotographs. 61
33577791 2021
Phacoemulsification, visco-goniosynechialysis, and goniotomy in patients with primary angle-closure glaucoma: A comparative study. 61
31578887 2021
Association Between Serum Lipid Levels and Patients With Primary Angle-Closure Glaucoma in China: A Cross Sectional, Case-Control Study. 61
33604350 2021
Responses to: Phacoemulsification Versus Phacotrabeculectomy in Primary Angle-closure Glaucoma With Cataract: Long-term Clinical Outcomes. 61
33003114 2021
Phacoemulsification Versus Phacotrabeculectomy in Primary Angle-closure Glaucoma With Cataract: Long-term Clinical Outcomes. 61
33003113 2021
Matched cohort study of Cataract surgery with and without trabecular micro-bypass stent implantation in primary angle-closure glaucoma. 61
33428885 2021
In-depth analysis of eight susceptibility loci of primary angle closure glaucoma in Han Chinese. 61
33227294 2021
Clinical features of uveal effusion detected in chinese primary angle-closure glaucoma patients. 61
33464233 2021
Clinical characteristics, rates of blindness, and geographic features of primary angle-closure disease in hospitals of the Chinese Glaucoma Study Consortium. 61
33485841 2021
Outcomes of primary trabeculectomy with mitomycin-C for primary angle closure glaucoma among supervised trainees in a tertiary eye center in Manila. 61
33515392 2021
Systemic inflammation in both open-angle and angle-closure glaucoma: role of platelet-to-lymphocyte ratio. 61
33393320 2021
Laminar and Prelaminar Tissue Characteristics of Glaucomatous Eyes Using Enhanced Depth Imaging OCT. 61
32827800 2021
Altered spontaneous neuronal activity and functional connectivity pattern in primary angle-closure glaucoma: a resting-state fMRI study. 61
32632634 2021
Recurrent Choroidal Detachment in Peritoneal Dialysis Patient with Hypervolemia and Dilutional Hypoalbuminemia: A Case Report. 61
33449586 2021
In vivo estimation of murine iris stiffness using finite element modeling. 61
33253706 2021
Iris stromal cell nuclei deform to more elongated shapes during pharmacologically-induced miosis and mydriasis. 61
33253707 2021
How Does Cataract Surgery Rate Affect Angle-closure Prevalence. 61
33031186 2021
Iris and its relevance to angle closure disease: a review. 61
32193222 2021
Peripapillary sclera exhibits a v-shaped configuration that is more pronounced in glaucoma eyes. 61
33334817 2020
Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations. 61
33396423 2020
Comparison of Peripapillary Choroidal Microvasculature Dropout in Primary Open-angle, Primary Angle-closure, and Pseudoexfoliation Glaucoma. 61
32890109 2020
Assessment of Reasons for Presentation in New Primary Glaucoma Patients and Identification of Risk Factors for Late Presentation. 61
33279673 2020
Comparison of Saccadic Eye Movements Among the High Tension Glaucoma, Primary Angle Closure Glaucoma, and Normal Tension Glaucoma. 61
33394842 2020
Achieving low target intraocular pressures in severe glaucoma. 61
33289400 2020
Optical Coherence Tomography Angiography and Visual Field Progression in Primary Angle Closure Glaucoma. 61
33273281 2020
Plateau Iris and Severity of Primary Angle Closure Glaucoma. 61
32735788 2020
Effects of Phacoemulsification Combined With Goniosynechialysis on Primary Angle-closure Glaucoma. 61
32910011 2020
Phaco-endocycloplasty versus Phacotrabeculectomy in Primary Angle-Closure Glaucoma: A Prospective Randomized Study. 61
32771456 2020
Cataract Surgery (Phacoemulsification with Intraocular Lens Implantation) Combined with Endoscopic Goniosynechialysis for Advanced Primary Angle-Closure Glaucoma. 61
33242682 2020
Safety and efficacy of incisional goniotomy as an adjunct with phacoemulsification in primary angle-closure glaucoma. 61
33181630 2020
Optical coherence tomography angiography of the macula in patients with primary angle closure glaucoma. 61
33142289 2020
Relationship between nailfold capillary morphology and retinal thickness and retinal vessel density in primary open-angle and angle-closure glaucoma. 61
32243735 2020
Clear lens extraction in eyes with primary angle closure and primary angle-closure glaucoma. 61
32339525 2020
Machine learning to determine relative contribution of modifiable and non-modifiable risk factors of major eye diseases. 61
33208351 2020
Glycerin-preserved Human-donor Corneoscleral Patch Grafts for Glaucoma Drainage Devices. 61
32890110 2020
Quantification of Retinal Microvascular Density Using Optic Coherence Tomography Angiography in Primary Angle Closure Disease. 61
33170750 2020
Combined Phacoemulsification With Goniosynechialysis Under Ophthalmic Endoscope for Primary Angle-closure Glaucoma After Failed Trabeculectomy. 61
32555057 2020
Macular vessel density and foveal avascular zone parameters in patients after acute primary angle closure determined by OCT angiography. 61
33127916 2020
Case report - Acute Corneal Subepithelial Hydrops (ACSH) during Micropulse Transscleral Cyclophotocoagulation (MPTSC). 61
33054758 2020
Diffusion tensor imaging of the visual pathway in dogs with primary angle-closure glaucoma. 61
32990378 2020
The Association of Single Nucleotide Polymorphisms in ABCC5 Gene with Primary Angle Closure Glaucoma and the Ocular Biometric Parameters in a Northern Chinese Population. 61
32906129 2020
Association Between 17-β-Estradiol and Interleukin-8 and Visual Field Progression in Postmenopausal Women with Primary Angle Closure Glaucoma. 61
32360861 2020
Prevalence of glaucoma in the elderly population in Taiwan: The Shihpai Eye Study. 61
32898085 2020
Six-Year Incidence and Risk Factors of Primary Glaucoma in the Singapore Indian Eye Study. 61
32947057 2020
Differences in Ocular Biometric Measurements among Subtypes of Primary Angle Closure Disease: The Chinese American Eye Study. 61
32942063 2020
Quantification of Iridotrabecular Contact in Primary Angle-Closure Disease. 61
32555058 2020

Variations for Primary Angle-Closure Glaucoma

Expression for Primary Angle-Closure Glaucoma

Search GEO for disease gene expression data for Primary Angle-Closure Glaucoma.

Pathways for Primary Angle-Closure Glaucoma

Pathways related to Primary Angle-Closure Glaucoma according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
Show member pathways
9.83 HTR3D HTR3C

GO Terms for Primary Angle-Closure Glaucoma

Biological processes related to Primary Angle-Closure Glaucoma according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of reactive oxygen species metabolic process GO:2000377 8.96 PARL CYP1B1
2 serotonin receptor signaling pathway GO:0007210 8.62 HTR3D HTR3C

Molecular functions related to Primary Angle-Closure Glaucoma according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 serotonin-gated cation-selective channel activity GO:0022850 8.62 HTR3D HTR3C

Sources for Primary Angle-Closure Glaucoma

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
70 Tocris
72 UMLS via Orphanet
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