MCID: CYS036
MIFTS: 42

Cystinosis, Nephropathic

Categories: Genetic diseases, Rare diseases, Nephrological diseases, Metabolic diseases

Aliases & Classifications for Cystinosis, Nephropathic

MalaCards integrated aliases for Cystinosis, Nephropathic:

Name: Cystinosis, Nephropathic 54 52
Nephropathic Cystinosis 50 24 29 69
Cystinosis, Atypical Nephropathic 54 29 13
Ctns 50 71
Lysosomal Cystine Transport Protein, Defect of 50
Defect of Lysosomal Cystine Transport Protein 71
Cystinosis, Infantile/early Onset/classic 24
Cystinosis, Infantile Nephropathic Type 24
Nephropathic Infantile Cystinosis 56
Cystinosis Infantile Nephropathic 71
Cystinosis Atypical Nephropathic 71
Cystinosis, Nephropathic Type 71
Cystinosin, Defect of 50
Defect of Cystinosin 71
Fanconi Syndrome 69
Cystinosin 13

Characteristics:

Orphanet epidemiological data:

56
nephropathic infantile cystinosis
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy; Age of death: adult;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
male infertility
incidence 1/100,000 - 1/200,000 live births
presentation in first year of life
three types of cystinosis are recognized - (1) infantile nephropathic , (2) juvenile or adolescent nephropathic , (3) adult nonnephropathic


HPO:

32
cystinosis, nephropathic:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Cystinosis, Nephropathic

OMIM : 54
Cystinosis has been classified as a lysosomal storage disorder on the basis of cytologic and other evidence pointing to the intralysosomal localization of stored cystine. Cystinosis differs from the other lysosomal diseases inasmuch as acid hydrolysis, the principal enzyme function of lysosomes, is not known to play a role in the metabolic disposition of cystine. The fact that plasma levels are well below saturation indicates that the defect is a cellular one. Within the cell, cystine is compartmentalized with acid phosphatase and is membrane-bound as demonstrated by electron microscopy. Ferritin accumulates in the same organelle which appears to be the lysosome. (219800)

MalaCards based summary : Cystinosis, Nephropathic, also known as nephropathic cystinosis, is related to non-nephropathic cystinosis and cystinosis, late-onset juvenile or adolescent nephropathic, and has symptoms including failure to thrive, cognitive impairment and pigmentary retinopathy. An important gene associated with Cystinosis, Nephropathic is CTNS (Cystinosin, Lysosomal Cystine Transporter). The drugs Cysteamine and Acetylcysteine have been mentioned in the context of this disorder. Affiliated tissues include eye, kidney and skin.

NIH Rare Diseases : 50 cystinosis is an inherited condition in which the body accumulates the amino acid cystine (a building block of proteins) within the cells. excess cystine forms crystals that can build up and damage cells. these crystals can negatively affect many systems in the body, especially the kidneys and eyes. there are three distinct types of cystinosis: nephropathic cystinosis, intermediate cystinosis, and non-nephropathic or ocular cystinosis. all three types of cystinosis are caused by mutations in the ctns gene and inherited in an autosomal recessive pattern. last updated: 11/11/2011

UniProtKB/Swiss-Prot : 71 Cystinosis, nephropathic type: A form of cystinosis, a lysosomal storage disease due to defective transport of cystine across the lysosomal membrane. This results in cystine accumulation and crystallization in the cells causing widespread tissue damage. The classical nephropathic form has onset in the first year of life and is characterized by a polyuro-polydipsic syndrome, marked height-weight growth delay, generalized impaired proximal tubular reabsorptive capacity, with severe fluid-electrolyte balance alterations, renal failure, ocular symptoms and other systemic complications.

Related Diseases for Cystinosis, Nephropathic

Diseases related to Cystinosis, Nephropathic via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 non-nephropathic cystinosis 12.1
2 cystinosis, late-onset juvenile or adolescent nephropathic 11.8
3 cystinosis 11.5
4 cystinosis, ocular nonnephropathic 11.1

Symptoms & Phenotypes for Cystinosis, Nephropathic

Symptoms via clinical synopsis from OMIM:

54

Skeletal:
delayed bone age
hypophosphatemic rickets

Abdomen- Liver:
hepatomegaly

Head And Neck- Eyes:
decreased visual acuity
photophobia
recurrent corneal erosions
peripheral retinopathy
corneal crystals

Laboratory- Abnormalities:
proteinuria
glucosuria
hyponatremia
microscopic hematuria
generalized aminoaciduria
more
Head And Neck- Face:
frontal bossing

Metabolic Features:
polyuria
polydipsia
recurrent episodes of acidosis
recurrent episodes of dehydration

Growth- Height:
normal birth length
short stature in first year of life

Abdomen- Pancreas:
pancreatic insufficiency

Growth- Other:
failure to thrive in first year of life

Skin Nails & Hair- Hair:
light hair pigmentation compared to unaffected sibs

Neurologic- Central Nervous System:
cerebral atrophy
normal intelligence
neurologic deterioration in longterm survivors
specific visual spatial processing defect

Abdomen- Spleen:
splenomegaly

Genitourinary- Kidneys:
renal failure
renal tubular fanconi syndrome
renal calculi (urate and calcium oxalate)

Muscle Soft Tissue:
swallowing difficulties
myopathy
muscle wasting

Skeletal- Limbs:
genu valgum
metaphyseal widening

Endocrine Features:
delayed puberty
primary hypothyroidism
insulin dependent diabetes mellitus

Growth- Weight:
normal birth weight

Chest- Ribs Sternum Clavicles And Scapulae:
rachitic rosary

Skin Nails & Hair- Skin:
decreased ability to sweat
light skin pigmentation compared to unaffected sibs

Voice:
hypophonic speech


Clinical features from OMIM:

219800

Human phenotypes related to Cystinosis, Nephropathic:

56 32 (show top 50) (show all 65)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 56 32 hallmark (90%) Very frequent (99-80%) HP:0001508
2 cognitive impairment 56 32 occasional (7.5%) Occasional (29-5%) HP:0100543
3 pigmentary retinopathy 56 32 frequent (33%) Frequent (79-30%) HP:0000580
4 renal tubular dysfunction 56 32 hallmark (90%) Very frequent (99-80%) HP:0000124
5 aminoaciduria 56 32 hallmark (90%) Very frequent (99-80%) HP:0003355
6 hyperphosphaturia 56 32 hallmark (90%) Very frequent (99-80%) HP:0003109
7 vomiting 56 32 hallmark (90%) Very frequent (99-80%) HP:0002013
8 hypokalemia 56 32 hallmark (90%) Very frequent (99-80%) HP:0002900
9 photophobia 56 32 hallmark (90%) Very frequent (99-80%) HP:0000613
10 constipation 56 32 hallmark (90%) Very frequent (99-80%) HP:0002019
11 dehydration 56 32 hallmark (90%) Very frequent (99-80%) HP:0001944
12 polydipsia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001959
13 hypophosphatemia 56 32 hallmark (90%) Very frequent (99-80%) HP:0002148
14 rickets 56 32 hallmark (90%) Very frequent (99-80%) HP:0002748
15 glycosuria 56 32 hallmark (90%) Very frequent (99-80%) HP:0003076
16 growth delay 56 32 hallmark (90%) Very frequent (99-80%) HP:0001510
17 hyperchloremic metabolic acidosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0004918
18 renal fanconi syndrome 56 32 hallmark (90%) Very frequent (99-80%) HP:0001994
19 corneal crystals 56 32 hallmark (90%) Very frequent (99-80%) HP:0000531
20 low-molecular-weight proteinuria 56 32 hallmark (90%) Very frequent (99-80%) HP:0003126
21 tubulointerstitial abnormality 56 32 hallmark (90%) Very frequent (99-80%) HP:0001969
22 abnormality of the cerebral white matter 56 32 occasional (7.5%) Occasional (29-5%) HP:0002500
23 abnormality of vitamin d metabolism 56 32 hallmark (90%) Very frequent (99-80%) HP:0100511
24 abnormality of thyroid physiology 56 32 frequent (33%) Frequent (79-30%) HP:0002926
25 short stature 32 HP:0004322
26 visual impairment 32 HP:0000505
27 dysphagia 32 HP:0002015
28 nephrolithiasis 32 HP:0000787
29 cerebral atrophy 32 HP:0002059
30 hepatomegaly 32 HP:0002240
31 splenomegaly 32 HP:0001744
32 proteinuria 32 HP:0000093
33 reduced visual acuity 32 HP:0007663
34 frontal bossing 32 HP:0002007
35 renal insufficiency 32 HP:0000083
36 genu valgum 32 HP:0002857
37 decreased plasma carnitine 32 HP:0003234
38 polyuria 32 HP:0000103
39 hyponatremia 32 HP:0002902
40 myopathy 32 HP:0003198
41 delayed puberty 32 HP:0000823
42 progressive neurologic deterioration 32 HP:0002344
43 diabetes mellitus 32 HP:0000819
44 microscopic hematuria 32 HP:0002907
45 generalized aminoaciduria 32 HP:0002909
46 hypohidrosis 32 HP:0000966
47 delayed skeletal maturation 32 HP:0002750
48 metaphyseal widening 32 HP:0003016
49 recurrent corneal erosions 32 HP:0000495
50 exocrine pancreatic insufficiency 32 HP:0001738

UMLS symptoms related to Cystinosis, Nephropathic:


polyuria, polydipsia, photophobia

Drugs & Therapeutics for Cystinosis, Nephropathic

Drugs for Cystinosis, Nephropathic (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 27)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cysteamine Approved, Investigational Phase 4,Phase 3,Phase 2,Phase 1 60-23-1 6058
2
Acetylcysteine Approved, Investigational Phase 4 616-91-1 12035
3 Antidotes Phase 4
4 Anti-Infective Agents Phase 4
5 Antioxidants Phase 4
6 Antiviral Agents Phase 4
7 Expectorants Phase 4
8 N-monoacetylcystine Phase 4
9 Protective Agents Phase 4
10 Respiratory System Agents Phase 4
11 cysteine Nutraceutical Phase 4
12
Dopamine Approved Phase 2,Phase 1 51-61-6, 62-31-7 681
13
Methamphetamine Approved, Illicit Phase 2,Phase 1 537-46-2 10836
14 Adrenergic Agents Phase 2,Phase 1
15 Autonomic Agents Phase 2,Phase 1
16 Central Nervous System Stimulants Phase 2,Phase 1
17 Dopamine Agents Phase 2,Phase 1
18 Dopamine Uptake Inhibitors Phase 2,Phase 1
19 Neurotransmitter Agents Phase 2,Phase 1
20 Neurotransmitter Uptake Inhibitors Phase 2,Phase 1
21 Ophthalmic Solutions Phase 2,Phase 1
22 Peripheral Nervous System Agents Phase 2,Phase 1,Early Phase 1
23 Pharmaceutical Solutions Phase 2
24 Tetrahydrozoline Phase 2,Phase 1
25
Capsaicin Approved Early Phase 1 404-86-4 1548943
26 Antipruritics Early Phase 1
27 Dermatologic Agents Early Phase 1

Interventional clinical trials:

(show all 24)

id Name Status NCT ID Phase Drugs
1 N Acetyl Cysteine for Cystinosis Patients Completed NCT01614431 Phase 4 N acetyl cysteine;N acetyl cysteine
2 Use of Cysteamine in the Treatment of Cystinosis Recruiting NCT00359684 Phase 4 Cysteamine
3 Phase 3 Study of Cysteamine Bitartrate Delayed-release (RP103) Compared to Cystagon® in Patients With Cystinosis Completed NCT01000961 Phase 3 Cystagon® (Cysteamine Bitartrate);Cysteamine Bitartrate Delayed-release Capsules (RP103)
4 Open-Label, Safety and Superior Effectiveness Study of Cysteamine Bitartrate Delayed-Release Capsules (RP103) in Cystinosis Completed NCT01733316 Phase 3 RP103;Cystagon®
5 Safety/Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naive Patients With Cystinosis Completed NCT01744782 Phase 3 RP103 Q12H
6 Long-Term Safety Follow-up Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) Completed NCT01197378 Phase 3 Cysteamine Bitartrate Delayed-release Capsules (RP103)
7 Cysteamine Eye Drops to Treat Corneal Crystals in Cystinosis Completed NCT00001213 Phase 2 Cysteamine
8 Pilot Study of Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of RP103 Compared to Cystagon® in Patients With Cystinosis Completed NCT00872729 Phase 1, Phase 2 Cystagon®;RP103
9 First Study of Oral Cysteamine in Cystic Fibrosis Completed NCT02212431 Phase 1, Phase 2 Cysteamine
10 Therapeutic Effect of Recombinant Human Growth Hormone (rhGH) on the Myopathy of Cystinosis Withdrawn NCT02124070 Phase 1, Phase 2 rh Growth Hormone
11 New Cysteamine Eye Drops Formulation to Treat Corneal Crystals in Cystinosis Completed NCT00001736 Phase 1 Cysteamine
12 A Cohort of Patients With Cystinosis : Compliance to Cysteamine and Neurological Complications Unknown status NCT02012114
13 The Functional Consequences of the CTNS-deletion for the TRPV1-receptor in Cystinosis Patients Completed NCT02533076 Early Phase 1
14 Clinical and Biological Study of Sub-pigmentation During Infantile Cystinosis Completed NCT00822250
15 Kidney Transplantation in Patients With Cystinosis Completed NCT00074516
16 The Role of Susceptibility to Thrombosis in the Pseudotumor Cerebri of Nephropathic Cystinosis: A Case-Control Study Completed NCT00071903
17 Establishment of a Database for Long-Term Monitoring of Patients With Nephropathic Cystinosis Completed NCT00004312
18 Randomized Study of New Formulation Ophthalmic Cysteamine Hydrochloride for Corneal Cystine Accumulation in Patients With Cystinosis Completed NCT00010426 cysteamine hydrochloride
19 Evaluation of Fanconi Syndrome and Cystinosis Completed NCT00004350
20 Study in Healthy Adults to Determine the Effect That Food Has on the Absorption and Delivery of the Drug Cystagon™ Completed NCT01432561 Cysteamine bitartrate
21 Efficacy of Topical Cysteamine in Nephropathic Cyctinosis Completed NCT02766855 Cysteamine
22 Salivary Proteins in Disease and Health Completed NCT00100204
23 Cure Cystinosis International Registry Recruiting NCT01327807
24 Biomarker for Patient With Cystinosis Disease or Highly Suspected for Cystinosis Disease Recruiting NCT02837523

Search NIH Clinical Center for Cystinosis, Nephropathic

Inferred drug relations via UMLS 69 / NDF-RT 48 :


Genetic Tests for Cystinosis, Nephropathic

Genetic tests related to Cystinosis, Nephropathic:

id Genetic test Affiliating Genes
1 Nephropathic Cystinosis 29 24 CTNS
2 Cystinosis, Atypical Nephropathic 29

Anatomical Context for Cystinosis, Nephropathic

MalaCards organs/tissues related to Cystinosis, Nephropathic:

39
Eye, Kidney, Skin, Bone, Skeletal Muscle, Thyroid

Publications for Cystinosis, Nephropathic

Articles related to Cystinosis, Nephropathic:

id Title Authors Year
1
What's your diagnosis? Cystinosis (nephropathic cystinosis). ( 16761632 )
2006

Variations for Cystinosis, Nephropathic

UniProtKB/Swiss-Prot genetic disease variations for Cystinosis, Nephropathic:

71 (show all 25)
id Symbol AA change Variation ID SNP ID
1 CTNS p.Gly169Asp VAR_010286 rs121908126
2 CTNS p.Ile133Phe VAR_010677
3 CTNS p.Ser139Phe VAR_010678 rs267606754
4 CTNS p.Leu158Pro VAR_010680 rs113994206
5 CTNS p.Trp182Arg VAR_010681 rs764168489
6 CTNS p.Asp205Asn VAR_010683 rs113994208
7 CTNS p.Asp305Gly VAR_010690
8 CTNS p.Asp305Tyr VAR_010691
9 CTNS p.Gly308Arg VAR_010692 rs746307931
10 CTNS p.Leu338Pro VAR_010694
11 CTNS p.Gly339Arg VAR_010695 rs121908127
12 CTNS p.Asp346Asn VAR_010698 rs757535731
13 CTNS p.Ser298Asn VAR_012315
14 CTNS p.Gly110Val VAR_037318 rs121908129
15 CTNS p.Gln222Arg VAR_037321
16 CTNS p.Asn288Lys VAR_037322
17 CTNS p.Arg151Gly VAR_067490
18 CTNS p.Gly157Asp VAR_067491
19 CTNS p.Tyr173Cys VAR_067492
20 CTNS p.Asn177Ser VAR_067493
21 CTNS p.Met287Ile VAR_067494
22 CTNS p.Gly308Val VAR_067495
23 CTNS p.Gly309Asp VAR_067496
24 CTNS p.Gly337Arg VAR_067497
25 CTNS p.Leu338Arg VAR_067498

ClinVar genetic disease variations for Cystinosis, Nephropathic:

6 (show all 33)
id Gene Variation Type Significance SNP ID Assembly Location
1 CTNS NM_001031681.2(CTNS): c.283G> T (p.Gly95Ter) single nucleotide variant Pathogenic rs121908124 GRCh37 Chromosome 17, 3558349: 3558349
2 CTNS CTNS, 2-BP DEL, 397TG deletion Pathogenic
3 CTNS NM_004937.2(CTNS): c.414G> A (p.Trp138Ter) single nucleotide variant Pathogenic rs113994205 GRCh37 Chromosome 17, 3558599: 3558599
4 CTNS CTNS, 4-BP DEL, 18GACT deletion Pathogenic
5 CTNS NC_000017.11: g.3600934_3658165del57232 deletion Pathogenic GRCh37 Chromosome 17, 3504228: 3561459
6 CTNS NM_001031681.2(CTNS): c.506G> A (p.Gly169Asp) single nucleotide variant Pathogenic rs121908126 GRCh37 Chromosome 17, 3559825: 3559825
7 CTNS CTNS, 5-BP DEL, NT545 deletion Pathogenic
8 CTNS NM_004937.2(CTNS): c.589G> A (p.Gly197Arg) single nucleotide variant Pathogenic/Likely pathogenic rs113994207 GRCh37 Chromosome 17, 3559997: 3559997
9 CTNS CTNS, -295G-C single nucleotide variant Pathogenic
10 CTNS NM_004937.2(CTNS): c.1015G> A (p.Gly339Arg) single nucleotide variant Pathogenic rs121908127 GRCh37 Chromosome 17, 3563574: 3563574
11 CTNS NM_001031681.2(CTNS): c.329G> T (p.Gly110Val) single nucleotide variant Pathogenic rs121908129 GRCh37 Chromosome 17, 3558395: 3558395
12 CTNS NM_004937.2(CTNS): c.416C> T (p.Ser139Phe) single nucleotide variant Pathogenic/Likely pathogenic rs267606754 GRCh37 Chromosome 17, 3558601: 3558601
13 CTNS NM_001031681.2(CTNS): c.198_218del21 (p.Ile67_Pro73del) deletion Pathogenic/Likely pathogenic rs113994204 GRCh37 Chromosome 17, 3552198: 3552218
14 CTNS NM_004937.2(CTNS): c.473T> C (p.Leu158Pro) single nucleotide variant Pathogenic rs113994206 GRCh37 Chromosome 17, 3559792: 3559792
15 CTNS NM_004937.2(CTNS): c.613G> A (p.Asp205Asn) single nucleotide variant Pathogenic rs113994208 GRCh37 Chromosome 17, 3560021: 3560021
16 CTNS NM_004937.2(CTNS): c.696dupC (p.Val233Argfs) duplication Pathogenic rs113994209 GRCh37 Chromosome 17, 3561313: 3561313
17 CTNS NM_004937.2(CTNS): c.559_561+24del27 deletion Pathogenic/Likely pathogenic rs113994211 GRCh37 Chromosome 17, 3559878: 3559904
18 CTNS NM_004937.2(CTNS): c.18_21delGACT (p.Thr7Phefs) deletion Pathogenic rs786204501 GRCh37 Chromosome 17, 3543518: 3543521
19 CTNS NM_001031681.2(CTNS): c.199_219del21 (p.Ile67_Pro73del) deletion Likely pathogenic rs786204550 GRCh37 Chromosome 17, 3552199: 3552219
20 CTNS NM_004937.2(CTNS): c.225+5_225+6delGTinsCC indel Likely pathogenic rs786204541 GRCh37 Chromosome 17, 3552230: 3552231
21 CTNS NM_004937.2(CTNS): c.292dupA (p.Thr98Asnfs) duplication Likely pathogenic rs786204434 GRCh37 Chromosome 17, 3558358: 3558358
22 CTNS NM_004937.2(CTNS): c.561+1delG deletion Likely pathogenic rs786204667 GRCh37 Chromosome 17, 3559881: 3559881
23 CTNS NM_004937.2(CTNS): c.614_616delACG (p.Asp205del) deletion Pathogenic/Likely pathogenic rs760256854 GRCh37 Chromosome 17, 3560022: 3560024
24 CTNS NM_004937.2(CTNS): c.809_811delCCT (p.Ser270del) deletion Likely pathogenic rs786204632 GRCh37 Chromosome 17, 3561426: 3561428
25 CTNS NM_004937.2(CTNS): c.926dupG (p.Ser310Glnfs) duplication Likely pathogenic rs786204420 GRCh37 Chromosome 17, 3563225: 3563225
26 CTNS NM_004937.2(CTNS): c.251delA (p.Asn84Thrfs) deletion Likely pathogenic rs1057516296 GRCh38 Chromosome 17, 3655023: 3655023
27 CTNS NM_004937.2(CTNS): c.329+2T> C single nucleotide variant Likely pathogenic rs955833453 GRCh38 Chromosome 17, 3655103: 3655103
28 CTNS NM_004937.2(CTNS): c.519_520delCA (p.Tyr173Terfs) deletion Pathogenic rs1057517093 GRCh38 Chromosome 17, 3656544: 3656545
29 CTNS NM_004937.2(CTNS): c.646dupA (p.Thr216Asnfs) duplication Pathogenic rs1057516993 GRCh38 Chromosome 17, 3656760: 3656760
30 CTNS NM_004937.2(CTNS): c.681+2T> C single nucleotide variant Likely pathogenic rs1057516723 GRCh37 Chromosome 17, 3560091: 3560091
31 CTNS NM_004937.2(CTNS): c.682-1G> A single nucleotide variant Likely pathogenic rs1057516771 GRCh37 Chromosome 17, 3561298: 3561298
32 CTNS NM_004937.2(CTNS): c.734G> A (p.Trp245Ter) single nucleotide variant Likely pathogenic rs763089013 GRCh38 Chromosome 17, 3658057: 3658057
33 CTNS NM_004937.2(CTNS): c.1102T> C (p.Ter368Gln) single nucleotide variant Likely pathogenic rs1057517330 GRCh37 Chromosome 17, 3563661: 3563661

Expression for Cystinosis, Nephropathic

Search GEO for disease gene expression data for Cystinosis, Nephropathic.

Pathways for Cystinosis, Nephropathic

GO Terms for Cystinosis, Nephropathic

Sources for Cystinosis, Nephropathic

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7 CNVD
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10 dbSNP
11 DGIdb
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38 LifeMap
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42 MeSH
43 MESH via Orphanet
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55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
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70 UMLS via Orphanet
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