MGCA7
MCID: 3MT024
MIFTS: 42

3-Methylglutaconic Aciduria, Type Vii (MGCA7)

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

Aliases & Classifications for 3-Methylglutaconic Aciduria, Type Vii

MalaCards integrated aliases for 3-Methylglutaconic Aciduria, Type Vii:

Name: 3-Methylglutaconic Aciduria, Type Vii 56 73
3-Methylglutaconic Aciduria, Type Vii, with Cataracts, Neurologic Involvement and Neutropenia 56 73 29 39
3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia 56 29 6 17
3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement and Neutropenia 12 73 15
Megcann 56 12 73
Mgca7 56 12 73
3-Methylglutaconic Aciduria Type 7 12 58
Mga7 12 58
3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia; Megcann 56
3-Methylglutaconic Aciduria-Cataract-Neurologic Involvement-Neutropenia Syndrome 58
3-Methylglutaconic Aciduria Type Vii 12
3-Methylglutaconic Aciduria 7 73

Characteristics:

Orphanet epidemiological data:

58
3-methylglutaconic aciduria type 7
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: early childhood,infantile;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
highly variable phenotype
onset at birth
onset in utero in severely affected patients
death often in childhood


HPO:

31
3-methylglutaconic aciduria, type vii:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Inborn errors of metabolism


Summaries for 3-Methylglutaconic Aciduria, Type Vii

OMIM : 56 3-Methylglutaconic aciduria (MGCA7) is an autosomal recessive inborn error of metabolism characterized primarily by increased levels of 3-methylglutaconic acid (3-MGA) associated with neurologic deterioration and neutropenia. The phenotype is highly variable: most patients have infantile onset of a progressive encephalopathy with various movement abnormalities and delayed psychomotor development, although rare patients with normal neurologic development have been reported. Other common, but variable, features include cataracts, seizures, and recurrent infections (summary by Wortmann et al., 2015 and Saunders et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA1 (250950). (616271)

MalaCards based summary : 3-Methylglutaconic Aciduria, Type Vii, also known as 3-methylglutaconic aciduria, type vii, with cataracts, neurologic involvement and neutropenia, is related to 3-methylglutaconic aciduria and clpb deficiency. An important gene associated with 3-Methylglutaconic Aciduria, Type Vii is CLPB (Caseinolytic Mitochondrial Matrix Peptidase Chaperone Subunit B), and among its related pathways/superpathways are Lysosome and TBC/RABGAPs. Affiliated tissues include bone marrow, bone and eye, and related phenotypes are cataract and nephrocalcinosis

Disease Ontology : 12 A 3-methylglutaconic aciduria that has material basis in homozygous or compound heterozygous mutation in the CLPB gene on chromosome 11q13.

UniProtKB/Swiss-Prot : 73 3-methylglutaconic aciduria 7: An autosomal recessive inborn error of metabolism with a highly variable phenotype. Primary disease symptoms are increased levels of 3-methylglutaconic acid, neurologic deterioration and neutropenia. Other common features include progressive encephalopathy, movement abnormalities, delayed psychomotor development, cataracts, seizures, and recurrent infections.

Related Diseases for 3-Methylglutaconic Aciduria, Type Vii

Diseases in the 3-Methylglutaconic Aciduria, Type Iii family:

3-Methylglutaconic Aciduria, Type I 3-Methylglutaconic Aciduria, Type Iv
3-Methylglutaconic Aciduria, Type V 3-Methylglutaconic Aciduria, Type Vii
3-Methylglutaconic Aciduria, Type Viii 3-Methylglutaconic Aciduria, Type Ix
3-Methylglutaconic Aciduria

Diseases related to 3-Methylglutaconic Aciduria, Type Vii via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 3-methylglutaconic aciduria 29.7 GGA2 CUBN CLPB
2 clpb deficiency 11.9
3 3-methylglutaconic aciduria, type viii 11.6
4 3-methylglutaconic aciduria, type iv 9.6 GGA2 GGA1
5 3-methylglutaconic aciduria, type i 9.1 GGA2 GGA1 CUBN CLPB

Graphical network of the top 20 diseases related to 3-Methylglutaconic Aciduria, Type Vii:



Diseases related to 3-Methylglutaconic Aciduria, Type Vii

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria, Type Vii

Human phenotypes related to 3-Methylglutaconic Aciduria, Type Vii:

58 31 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cataract 58 31 hallmark (90%) Very frequent (99-80%) HP:0000518
2 nephrocalcinosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000121
3 neutropenia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001875
4 renal cyst 58 31 hallmark (90%) Very frequent (99-80%) HP:0000107
5 3-methylglutaconic aciduria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003535
6 congenital microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0011451
7 global developmental delay 31 hallmark (90%) HP:0001263
8 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
9 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
10 developmental regression 58 31 occasional (7.5%) Frequent (79-30%) HP:0002376
11 abnormal pyramidal sign 58 31 frequent (33%) Frequent (79-30%) HP:0007256
12 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
13 myoclonus 58 31 frequent (33%) Frequent (79-30%) HP:0001336
14 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
15 growth delay 58 31 frequent (33%) Frequent (79-30%) HP:0001510
16 increased serum lactate 58 31 frequent (33%) Frequent (79-30%) HP:0002151
17 cerebellar atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0001272
18 encephalopathy 58 31 frequent (33%) Frequent (79-30%) HP:0001298
19 bone marrow hypocellularity 58 31 frequent (33%) Frequent (79-30%) HP:0005528
20 choreoathetosis 58 31 frequent (33%) Frequent (79-30%) HP:0001266
21 delayed gross motor development 58 31 frequent (33%) Frequent (79-30%) HP:0002194
22 cerebral atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002059
23 abnormality of the basal ganglia 58 31 frequent (33%) Frequent (79-30%) HP:0002134
24 progressive extrapyramidal movement disorder 58 31 frequent (33%) Frequent (79-30%) HP:0007153
25 opisthotonus 58 31 frequent (33%) Frequent (79-30%) HP:0002179
26 infection associated neutropenia 58 31 frequent (33%) Frequent (79-30%) HP:0410256
27 hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000821
28 renal insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0000083
29 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
30 hepatic steatosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001397
31 elevated hepatic transaminase 58 31 occasional (7.5%) Occasional (29-5%) HP:0002910
32 neonatal hypoglycemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001998
33 respiratory failure 58 31 occasional (7.5%) Occasional (29-5%) HP:0002878
34 cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001638
35 abnormal facial shape 31 occasional (7.5%) HP:0001999
36 recurrent infections 31 occasional (7.5%) HP:0002719
37 seizure 31 occasional (7.5%) HP:0001250
38 pneumothorax 58 31 very rare (1%) Very rare (<4-1%) HP:0002107
39 spasticity 58 31 Frequent (79-30%) HP:0001257
40 abnormality of extrapyramidal motor function 58 31 Frequent (79-30%) HP:0002071
41 seizures 58 Occasional (29-5%)
42 microcephaly 31 HP:0000252
43 neonatal hypotonia 31 HP:0001319
44 hypertonia 58 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
intellectual disability
spasticity
cerebellar atrophy
cerebral atrophy
extrapyramidal signs
more
Abdomen Gastrointestinal:
poor feeding

Muscle Soft Tissue:
hypotonia, neonatal
increased muscle tone, neonatal (in severely affected patients)

Head And Neck Face:
dysmorphic facial features (in some patients)

Laboratory Abnormalities:
increased urinary 2-methylglutaconic acid

Head And Neck Head:
microcephaly

Immunology:
recurrent infections (in some patients)
neutropenia (in most patients)
bone marrow shows deficient granulopoiesis

Growth Other:
poor growth

Head And Neck Eyes:
cataracts (in most patients)

Clinical features from OMIM:

616271

Drugs & Therapeutics for 3-Methylglutaconic Aciduria, Type Vii

Search Clinical Trials , NIH Clinical Center for 3-Methylglutaconic Aciduria, Type Vii

Genetic Tests for 3-Methylglutaconic Aciduria, Type Vii

Genetic tests related to 3-Methylglutaconic Aciduria, Type Vii:

# Genetic test Affiliating Genes
1 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia 29 CLPB
2 3-Methylglutaconic Aciduria, Type Vii, with Cataracts, Neurologic Involvement and Neutropenia 29

Anatomical Context for 3-Methylglutaconic Aciduria, Type Vii

MalaCards organs/tissues related to 3-Methylglutaconic Aciduria, Type Vii:

40
Bone Marrow, Bone, Eye, Brain

Publications for 3-Methylglutaconic Aciduria, Type Vii

Articles related to 3-Methylglutaconic Aciduria, Type Vii:

# Title Authors PMID Year
1
Disruption of CLPB is associated with congenital microcephaly, severe encephalopathy and 3-methylglutaconic aciduria. 6 56
25650066 2015
2
CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. 6 56
25597510 2015
3
CLPB variants associated with autosomal-recessive mitochondrial disorder with cataract, neutropenia, epilepsy, and methylglutaconic aciduria. 56 6
25597511 2015
4
CLPB Deficiency 6
27891836 2016
5
[Clinical and genetic analysis of an infant with 3-methylglutaconic aciduria type VII]. 61
32219827 2020

Variations for 3-Methylglutaconic Aciduria, Type Vii

ClinVar genetic disease variations for 3-Methylglutaconic Aciduria, Type Vii:

6 (show top 50) (show all 117) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CLPB NM_001258392.3(CLPB):c.1167+5G>TSNV Pathogenic 574472 rs1565424666 11:72013343-72013343 11:72302299-72302299
2 CLPB NM_001258392.3(CLPB):c.646+7323G>TSNV Pathogenic 571241 rs374473067 11:72084002-72084002 11:72372958-72372958
3 CLPB NM_001258392.3(CLPB):c.934C>T (p.Arg312Ter)SNV Pathogenic 802698 11:72028204-72028204 11:72317160-72317160
4 CLPB NC_000011.10:g.(?_72372905)_(72380404_?)deldeletion Pathogenic 830973 11:72083949-72091448
5 CLPB NM_001258392.3(CLPB):c.646+7310G>ASNV Pathogenic 851107 11:72084015-72084015 11:72372971-72372971
6 CLPB NM_001258392.3(CLPB):c.193G>T (p.Gly65Ter)SNV Pathogenic 856343 11:72145326-72145326 11:72434282-72434282
7 CLPB NM_001258392.3(CLPB):c.1215_1217inv (p.Glu405_Gly406delinsAspPro)inversion Pathogenic 187780 11:72012959-72012961 11:72301915-72301917
8 CLPB NM_001258392.3(CLPB):c.1847G>T (p.Gly616Val)SNV Pathogenic 187781 rs759500860 11:72004598-72004598 11:72293554-72293554
9 CLPB NM_001258392.3(CLPB):c.1682C>T (p.Ala561Val)SNV Pathogenic 187782 rs748010262 11:72005169-72005169 11:72294125-72294125
10 CLPB NM_001258392.3(CLPB):c.1143G>A (p.Met381Ile)SNV Pathogenic 187783 rs786205137 11:72013372-72013372 11:72302328-72302328
11 CLPB NM_001258392.3(CLPB):c.1760A>G (p.Tyr587Cys)SNV Pathogenic 187784 rs786205138 11:72005091-72005091 11:72294047-72294047
12 CLPB NC_000011.10:g.(?_72293347)_(72434494_?)deldeletion Pathogenic 642638 11:72004391-72145538 11:72293347-72434494
13 CLPB NM_001258392.3(CLPB):c.1159C>T (p.Arg387Ter)SNV Pathogenic 187786 rs200203460 11:72013356-72013356 11:72302312-72302312
14 CLPB NM_001258392.3(CLPB):c.1955T>A (p.Ile652Asn)SNV Pathogenic 279613 rs886041120 11:72004490-72004490 11:72293446-72293446
15 CLPB NM_001258392.3(CLPB):c.1847dup (p.Cys617fs)duplication Pathogenic 279612 rs886041119 11:72004597-72004598 11:72293553-72293554
16 CLPB NM_001258392.3(CLPB):c.1825G>A (p.Glu609Lys)SNV Pathogenic 279611 rs375934856 11:72004620-72004620 11:72293576-72293576
17 CLPB NM_001258392.3(CLPB):c.1411G>A (p.Glu471Lys)SNV Pathogenic 279608 rs748915609 11:72006611-72006611 11:72295567-72295567
18 CLPB NM_001258392.3(CLPB):c.1366T>C (p.Cys456Arg)SNV Pathogenic 279607 rs886041118 11:72006656-72006656 11:72295612-72295612
19 CLPB NM_001258392.3(CLPB):c.725A>G (p.Tyr242Cys)SNV Pathogenic 279606 rs777313457 11:72069974-72069974 11:72358930-72358930
20 CLPB NM_001258392.3(CLPB):c.715G>A (p.Ala239Thr)SNV Pathogenic 279605 rs886041117 11:72069984-72069984 11:72358940-72358940
21 CLPB NM_001258392.3(CLPB):c.658C>T (p.Arg220Ter)SNV Pathogenic 279604 rs777202372 11:72070041-72070041 11:72358997-72358997
22 CLPB NM_001258392.3(CLPB):c.871A>T (p.Lys291Ter)SNV Pathogenic 187788 rs786205139 11:72040753-72040753 11:72329709-72329709
23 CLPB NM_001258392.3(CLPB):c.1595del (p.Ile532fs)deletion Pathogenic 192392 rs876657402 11:72005454-72005454 11:72294410-72294410
24 CLPB NM_001258392.3(CLPB):c.1132A>G (p.Arg378Gly)SNV Pathogenic/Likely pathogenic 187785 rs144078282 11:72013383-72013383 11:72302339-72302339
25 CLPB NM_001258392.3(CLPB):c.1610A>G (p.Tyr537Cys)SNV Likely pathogenic 279609 rs150857620 11:72005439-72005439 11:72294395-72294395
26 CLPB NM_001258392.3(CLPB):c.130G>A (p.Glu44Lys)SNV Uncertain significance 841085 11:72145389-72145389 11:72434345-72434345
27 CLPB NM_001258392.3(CLPB):c.2T>C (p.Met1Thr)SNV Uncertain significance 855897 11:72145517-72145517 11:72434473-72434473
28 CLPB NM_001258392.3(CLPB):c.1591C>T (p.Arg531Trp)SNV Uncertain significance 869400 11:72005458-72005458 11:72294414-72294414
29 CLPB NM_001258392.3(CLPB):c.1361T>C (p.Ile454Thr)SNV Uncertain significance 915353 11:72006661-72006661 11:72295617-72295617
30 CLPB NM_001258392.3(CLPB):c.1792C>T (p.Arg598Cys)SNV Uncertain significance 279610 rs150343959 11:72004653-72004653 11:72293609-72293609
31 CLPB NM_001258392.3(CLPB):c.713C>T (p.Thr238Met)SNV Uncertain significance 187787 rs200032855 11:72069986-72069986 11:72358942-72358942
32 CLPB NM_001258392.3(CLPB):c.646+7290C>TSNV Uncertain significance 843629 11:72084035-72084035 11:72372991-72372991
33 CLPB NM_001258392.3(CLPB):c.646+7273G>CSNV Uncertain significance 852817 11:72084052-72084052 11:72373008-72373008
34 CLPB NM_001258392.3(CLPB):c.254C>T (p.Ala85Val)SNV Uncertain significance 848832 11:72145265-72145265 11:72434221-72434221
35 CLPB NM_001258392.3(CLPB):c.2033A>G (p.Ter678Trp)SNV Uncertain significance 859467 11:72004412-72004412 11:72293368-72293368
36 CLPB NM_001258392.3(CLPB):c.1718G>A (p.Arg573His)SNV Uncertain significance 849887 11:72005133-72005133 11:72294089-72294089
37 CLPB NM_001258392.3(CLPB):c.1552A>G (p.Ile518Val)SNV Uncertain significance 850342 11:72005672-72005672 11:72294628-72294628
38 CLPB NM_001258392.3(CLPB):c.1485G>A (p.Leu495=)SNV Uncertain significance 855156 11:72006537-72006537 11:72295493-72295493
39 CLPB NM_001258392.3(CLPB):c.1463G>A (p.Arg488His)SNV Uncertain significance 862909 11:72006559-72006559 11:72295515-72295515
40 CLPB NM_001258392.3(CLPB):c.1018G>A (p.Asp340Asn)SNV Uncertain significance 855610 11:72019619-72019619 11:72308575-72308575
41 CLPB NM_001258392.3(CLPB):c.896G>A (p.Arg299His)SNV Uncertain significance 844712 11:72028242-72028242 11:72317198-72317198
42 CLPB NM_001258392.3(CLPB):c.806G>T (p.Gly269Val)SNV Uncertain significance 860269 11:72040818-72040818 11:72329774-72329774
43 CLPB NM_001258392.3(CLPB):c.751A>G (p.Thr251Ala)SNV Uncertain significance 859943 11:72069948-72069948 11:72358904-72358904
44 CLPB NM_001258392.3(CLPB):c.370G>T (p.Val124Phe)SNV Uncertain significance 566693 rs139361195 11:72145149-72145149 11:72434105-72434105
45 CLPB NM_001258392.3(CLPB):c.359C>G (p.Ala120Gly)SNV Uncertain significance 567676 rs1565107812 11:72145160-72145160 11:72434116-72434116
46 CLPB NM_001258392.3(CLPB):c.1292C>T (p.Pro431Leu)SNV Uncertain significance 583353 rs746582120 11:72012884-72012884 11:72301840-72301840
47 CLPB NM_001258392.3(CLPB):c.646+6T>CSNV Uncertain significance 570992 rs374982363 11:72091319-72091319 11:72380275-72380275
48 CLPB NM_001258392.3(CLPB):c.1958T>C (p.Ile653Thr)SNV Uncertain significance 644706 11:72004487-72004487 11:72293443-72293443
49 CLPB NM_001258392.3(CLPB):c.1859G>A (p.Arg620His)SNV Uncertain significance 665509 11:72004586-72004586 11:72293542-72293542
50 CLPB NM_001258392.3(CLPB):c.1592G>A (p.Arg531Gln)SNV Uncertain significance 643064 11:72005457-72005457 11:72294413-72294413

UniProtKB/Swiss-Prot genetic disease variations for 3-Methylglutaconic Aciduria, Type Vii:

73 (show all 11)
# Symbol AA change Variation ID SNP ID
1 CLPB p.Thr268Met VAR_073397 rs200032855
2 CLPB p.Tyr272Cys VAR_073398 rs777313457
3 CLPB p.Arg408Gly VAR_073399 rs144078282
4 CLPB p.Met411Ile VAR_073400 rs786205137
5 CLPB p.Cys486Arg VAR_073402 rs886041118
6 CLPB p.Glu501Lys VAR_073403 rs748915609
7 CLPB p.Tyr567Cys VAR_073404 rs150857620
8 CLPB p.Ala591Val VAR_073405 rs748010262
9 CLPB p.Tyr617Cys VAR_073406 rs786205138
10 CLPB p.Gly646Val VAR_073407 rs759500860
11 CLPB p.Ile682Asn VAR_073408 rs886041120

Expression for 3-Methylglutaconic Aciduria, Type Vii

Search GEO for disease gene expression data for 3-Methylglutaconic Aciduria, Type Vii.

Pathways for 3-Methylglutaconic Aciduria, Type Vii

Pathways related to 3-Methylglutaconic Aciduria, Type Vii according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.06 GGA2 GGA1
2 10.3 GGA2 GGA1

GO Terms for 3-Methylglutaconic Aciduria, Type Vii

Cellular components related to 3-Methylglutaconic Aciduria, Type Vii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.26 YIPF5 GGA2 GGA1 CUBN
2 endosome membrane GO:0010008 8.8 GGA2 GGA1 CUBN

Biological processes related to 3-Methylglutaconic Aciduria, Type Vii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 vesicle-mediated transport GO:0016192 9.43 YIPF5 GGA2 GGA1
2 protein transport GO:0015031 9.26 YIPF5 GGA2 GGA1 CUBN
3 Golgi to plasma membrane protein transport GO:0043001 9.16 GGA2 GGA1
4 protein localization to cell surface GO:0034394 8.62 GGA2 GGA1

Molecular functions related to 3-Methylglutaconic Aciduria, Type Vii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ADP-ribosylation factor binding GO:0030306 8.62 GGA2 GGA1

Sources for 3-Methylglutaconic Aciduria, Type Vii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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