MCID: ATS282
MIFTS: 42

Autosomal Recessive Malignant Osteopetrosis

Categories: Blood diseases, Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Autosomal Recessive Malignant Osteopetrosis

Summaries for Autosomal Recessive Malignant Osteopetrosis

MalaCards based summary : Autosomal Recessive Malignant Osteopetrosis, also known as infantile malignant osteopetrosis, is related to osteopetrosis and osteopetrosis, autosomal recessive 5. An important gene associated with Autosomal Recessive Malignant Osteopetrosis is TCIRG1 (T Cell Immune Regulator 1, ATPase H+ Transporting V0 Subunit A3), and among its related pathways/superpathways are Ion channel transport and Rheumatoid arthritis. The drugs Busulfan and Vidarabine have been mentioned in the context of this disorder. Affiliated tissues include bone, skin and eye, and related phenotypes are macrocephaly and abnormality of epiphysis morphology

Related Diseases for Autosomal Recessive Malignant Osteopetrosis

Diseases in the Osteopetrosis family:

Osteopetrosis, Autosomal Dominant 2 Osteopetrosis, Autosomal Recessive 1
Osteopetrosis, Autosomal Recessive 2 Osteopetrosis, Autosomal Recessive 5
Osteopetrosis, Autosomal Recessive 3 Osteopetrosis, Autosomal Dominant 1
Osteopetrosis, Autosomal Recessive 4 Osteopetrosis, Autosomal Recessive 6
Osteopetrosis, Autosomal Recessive 7 Osteopetrosis, Autosomal Recessive 8
Osteopetrosis, Autosomal Dominant 3 Clcn7-Related Osteopetrosis
Autosomal Recessive Malignant Osteopetrosis

Diseases related to Autosomal Recessive Malignant Osteopetrosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 19)
# Related Disease Score Top Affiliating Genes
1 osteopetrosis 29.5 CLCN7 SNX10 TCIRG1 TNFSF11
2 osteopetrosis, autosomal recessive 5 11.9
3 osteopetrosis, autosomal recessive 1 11.9
4 osteopetrosis, autosomal recessive 4 11.4
5 hematopoietic stem cell transplantation 10.1
6 pulmonary hypertension, primary, 1 10.0
7 juvenile myelomonocytic leukemia 10.0
8 choanal atresia, posterior 10.0
9 leukemia 10.0
10 thrombocytopenia 10.0
11 osteomyelitis 10.0
12 rickets 10.0
13 osteopetrosis, autosomal recessive 6 9.9 CLCN7 TCIRG1
14 osteopetrosis, autosomal recessive 3 9.9 CLCN7 TCIRG1
15 osteopetrosis, autosomal recessive 2 9.8 CLCN7 TNFSF11
16 bone disease 9.7 CLCN7 TNFSF11
17 osteopetrosis, autosomal dominant 2 9.7 CLCN7 TCIRG1 TNFSF11
18 endosteal hyperostosis, autosomal dominant 9.7 CLCN7 TCIRG1 TNFSF11
19 bone remodeling disease 9.6 CLCN7 TCIRG1 TNFSF11

Graphical network of the top 20 diseases related to Autosomal Recessive Malignant Osteopetrosis:



Diseases related to Autosomal Recessive Malignant Osteopetrosis

Symptoms & Phenotypes for Autosomal Recessive Malignant Osteopetrosis

Human phenotypes related to Autosomal Recessive Malignant Osteopetrosis:

59 32 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000256
2 abnormality of epiphysis morphology 59 32 hallmark (90%) Very frequent (99-80%) HP:0005930
3 hydrocephalus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000238
4 nystagmus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000639
5 tremor 59 32 hallmark (90%) Very frequent (99-80%) HP:0001337
6 hearing impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0000365
7 splenomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001744
8 recurrent respiratory infections 59 32 hallmark (90%) Very frequent (99-80%) HP:0002205
9 hepatomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0002240
10 bowing of the long bones 59 32 hallmark (90%) Very frequent (99-80%) HP:0006487
11 visual impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0000505
12 abnormality of visual evoked potentials 59 32 hallmark (90%) Very frequent (99-80%) HP:0000649
13 hypophosphatemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002148
14 cranial nerve paralysis 59 32 occasional (7.5%) Occasional (29-5%) HP:0006824
15 anemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001903
16 pallor 59 32 hallmark (90%) Very frequent (99-80%) HP:0000980
17 pulmonary arterial hypertension 59 32 occasional (7.5%) Occasional (29-5%) HP:0002092
18 abnormal blistering of the skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0008066
19 abnormality of the metaphysis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000944
20 delayed eruption of teeth 59 32 hallmark (90%) Very frequent (99-80%) HP:0000684
21 narrow chest 59 32 hallmark (90%) Very frequent (99-80%) HP:0000774
22 reduced bone mineral density 59 32 hallmark (90%) Very frequent (99-80%) HP:0004349
23 growth delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001510
24 abnormality of temperature regulation 59 32 hallmark (90%) Very frequent (99-80%) HP:0004370
25 apnea 59 32 occasional (7.5%) Occasional (29-5%) HP:0002104
26 hypocalcemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002901
27 abnormality of the ribs 59 32 hallmark (90%) Very frequent (99-80%) HP:0000772
28 recurrent fractures 59 32 hallmark (90%) Very frequent (99-80%) HP:0002757
29 otitis media 59 32 hallmark (90%) Very frequent (99-80%) HP:0000388
30 bruising susceptibility 59 32 occasional (7.5%) Occasional (29-5%) HP:0000978
31 bone pain 59 32 hallmark (90%) Very frequent (99-80%) HP:0002653
32 craniosynostosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0001363
33 pulmonary artery stenosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0004415
34 lymphadenopathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0002716
35 osteopetrosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0011002
36 optic nerve compression 59 32 hallmark (90%) Very frequent (99-80%) HP:0007807
37 chronic rhinitis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002257
38 abnormality of hair texture 59 32 hallmark (90%) Very frequent (99-80%) HP:0010719
39 premature loss of primary teeth 59 32 hallmark (90%) Very frequent (99-80%) HP:0006323
40 opsoclonus 59 32 hallmark (90%) Very frequent (99-80%) HP:0010543
41 abnormality of metabolism/homeostasis 59 Very frequent (99-80%)
42 abnormality of movement 59 Very frequent (99-80%)
43 abnormality of the pulmonary valve 59 Occasional (29-5%)
44 abnormal pulmonary valve morphology 32 occasional (7.5%) HP:0001641

MGI Mouse Phenotypes related to Autosomal Recessive Malignant Osteopetrosis:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.67 CLCN7 SNX10 TCIRG1 TNFSF11
2 growth/size/body region MP:0005378 9.62 CLCN7 SNX10 TCIRG1 TNFSF11
3 hematopoietic system MP:0005397 9.56 CLCN7 SNX10 TCIRG1 TNFSF11
4 immune system MP:0005387 9.46 CLCN7 SNX10 TCIRG1 TNFSF11
5 limbs/digits/tail MP:0005371 9.13 CLCN7 TCIRG1 TNFSF11
6 skeleton MP:0005390 8.92 CLCN7 SNX10 TCIRG1 TNFSF11

Drugs & Therapeutics for Autosomal Recessive Malignant Osteopetrosis

Drugs for Autosomal Recessive Malignant Osteopetrosis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 29)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Busulfan Approved, Investigational Phase 2, Phase 3 55-98-1 2478
2
Vidarabine Approved, Investigational Phase 2, Phase 3 24356-66-9 32326 21704
3
Fludarabine Approved Phase 2, Phase 3,Phase 3 75607-67-9, 21679-14-1 30751
4
alemtuzumab Approved, Investigational Phase 2, Phase 3 216503-57-0
5
Cyclophosphamide Approved, Investigational Phase 2, Phase 3 6055-19-2, 50-18-0 2907
6 Antiviral Agents Phase 2, Phase 3
7 Antineoplastic Agents, Alkylating Phase 2, Phase 3
8 Immunosuppressive Agents Phase 2, Phase 3
9 Antimetabolites, Antineoplastic Phase 2, Phase 3
10 Antirheumatic Agents Phase 2, Phase 3
11 Anti-Infective Agents Phase 2, Phase 3
12 Alkylating Agents Phase 2, Phase 3
13 Antimetabolites Phase 2, Phase 3
14 Immunologic Factors Phase 2, Phase 3
15
rituximab Approved Phase 2 174722-31-7 10201696
16
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
17
Tocopherol Approved, Investigational Phase 2 1406-66-2 14986
18
Acetylcysteine Approved, Investigational Phase 2 616-91-1 12035
19
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
20
Clofarabine Approved, Investigational Phase 2 123318-82-1 119182
21
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
22 Tocotrienol Investigational Phase 2 6829-55-6
23 Tocopherols Phase 2
24 Antilymphocyte Serum Phase 2
25 Vitamins Phase 2
26 Tocotrienols Phase 2
27 N-monoacetylcystine Phase 2
28 Alpha-lipoic Acid Phase 2
29 Thioctic Acid Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Allogeneic Transplantation For Severe Osteopetrosis Unknown status NCT00775931 Phase 2, Phase 3 Campath-1H;Cyclophosphamide;Busulfan;Fludarabine monophosphate
2 MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis Recruiting NCT02171104 Phase 2 IMD Preparative Regimen;Osteopetrosis Only Preparative Regimen;Osteopetrosis Haploidentical Only Preparative Regimen;cALD SR-A (Standard-Risk, Regimen A);cALD SR-B (Standard-Risk, Regimen B);cALD HR-D (High-Risk, Regimen C);cALD HR-D (High-Risk, Regimen D)
3 Reduced Intensity AlloTransplant For Osteopetrosis Terminated NCT00638820 Phase 2 Campath, Busulfan, Clofarabine

Search NIH Clinical Center for Autosomal Recessive Malignant Osteopetrosis

Genetic Tests for Autosomal Recessive Malignant Osteopetrosis

Anatomical Context for Autosomal Recessive Malignant Osteopetrosis

MalaCards organs/tissues related to Autosomal Recessive Malignant Osteopetrosis:

41
Bone, Skin, Eye, Bone Marrow, T Cells

Publications for Autosomal Recessive Malignant Osteopetrosis

Articles related to Autosomal Recessive Malignant Osteopetrosis:

(show all 37)
# Title Authors Year
1
Whole exome sequencing identified two novel homozygous missense variants in the same codon of CLCN7 underlying autosomal recessive infantile malignant osteopetrosis in a Pakistani family. ( 29926385 )
2018
2
Ophthalmic phenotype of TCIRG1 gene mutations in Chinese infantile malignant osteopetrosis. ( 30539151 )
2018
3
Targeting NSG Mice Engrafting Cells with a Clinically Applicable Lentiviral Vector Corrects Osteoclasts in Infantile Malignant Osteopetrosis. ( 28726516 )
2017
4
[Analysis of TCIRG1 gene mutation in a Chinese family affected with infantile malignant osteopetrosis]. ( 28604959 )
2017
5
Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy. ( 27541021 )
2016
6
Improved Outcomes of Hematopoietic Stem Cell Transplantation in Patients With Infantile Malignant Osteopetrosis Using Fludarabine-Based Conditioning. ( 26485304 )
2015
7
Identification and Characterization of Mutations in the CLCN7 Gene in a Taiwanese Patient with Infantile Malignant Osteopetrosis. ( 26365571 )
2015
8
A novel mutation and a known mutation in the CLCN7 gene associated with relatively stable infantile malignant osteopetrosis in a Chinese patient. ( 26477479 )
2015
9
Unmistakable Morphology? Infantile Malignant Osteopetrosis Resembling Juvenile Myelomonocytic Leukemia in Infants. ( 25982139 )
2015
10
A fatal case of infantile malignant osteopetrosis complicated by pulmonary arterial hypertension after hematopoietic stem cell transplantation. ( 25504019 )
2014
11
Identification of Novel Mutation in Autosomal Recessive Infantile Malignant Osteopetrosis. ( 24101165 )
2013
12
Lentiviral gene transfer of TCIRG1 into peripheral blood CD34(+) cells restores osteoclast function in infantile malignant osteopetrosis. ( 23907031 )
2013
13
Infantile malignant osteopetrosis. ( 23721911 )
2013
14
Infantile malignant osteopetrosis: a rare cause of neonatal hypocalcemia. ( 23329773 )
2012
15
Infantile malignant osteopetrosis: report of 2 cases with osteomyelitis of the jaws. ( 22828766 )
2012
16
Novel mutation of TCIRG1 and clinical pictures of two infantile malignant osteopetrosis patients. ( 21042819 )
2011
17
Novel mutations in Indian patients with autosomal recessive infantile malignant osteopetrosis. ( 20424301 )
2010
18
Osteopetrorickets: infantile malignant osteopetrosis paradoxically complicated by rickets. ( 19756570 )
2010
19
A single-center experience in 20 patients with infantile malignant osteopetrosis. ( 19507210 )
2009
20
Rare gross deletion in T-cell immune regulator-1 gene in Iranian family with infantile malignant osteopetrosis. ( 18946580 )
2008
21
Infantile autosomal-recessive malignant osteopetrosis. ( 17592489 )
2007
22
Chloride channel CICN7 mutations in a Korean patient with infantile malignant osteopetrosis initially presenting with neonatal thrombocytopenia. ( 15116126 )
2004
23
Hematological defects in the oc/oc mouse, a model of infantile malignant osteopetrosis. ( 15284856 )
2004
24
Osteoclast morphology in autosomal recessive malignant osteopetrosis due to a TCIRG1 gene mutation. ( 12687885 )
2003
25
Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis. ( 12552563 )
2003
26
Infantile Malignant Osteopetrosis: Delay in Diagnosis Eliminates Chance of Cure. ( 27265338 )
2003
27
Infantile Malignant Osteopetrosis: Delay in Diagnosis Eliminates Chance of Cure. ( 27264978 )
2002
28
Novel mutations in the a3 subunit of vacuolar H(+)-adenosine triphosphatase in a Japanese patient with infantile malignant osteopetrosis. ( 11856654 )
2002
29
Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis. ( 10942435 )
2000
30
Distal phalangeal resorption in an adult with infantile malignant osteopetrosis: a case report. ( 9523972 )
1998
31
Bone marrow transplantation for infantile malignant osteopetrosis. ( 7583393 )
1995
32
Infantile malignant osteopetrosis presenting as bilateral choanal atresia: Report of two cases. ( 17588000 )
1993
33
Chorioretinal degeneration in infantile malignant osteopetrosis. ( 2368817 )
1990
34
Successful treatment of infantile malignant osteopetrosis by bone-marrow transplantation. A case report. ( 3281954 )
1988
35
Allogeneic bone-marrow transplantation in infantile malignant osteopetrosis. ( 6131166 )
1983
36
The pathogenesis of infantile malignant osteopetrosis: bone mineral metabolism and complications in five infants. ( 6270498 )
1981
37
Successful bone-marrow transplantation for infantile malignant osteopetrosis. ( 6986555 )
1980

Variations for Autosomal Recessive Malignant Osteopetrosis

Expression for Autosomal Recessive Malignant Osteopetrosis

Search GEO for disease gene expression data for Autosomal Recessive Malignant Osteopetrosis.

Pathways for Autosomal Recessive Malignant Osteopetrosis

Pathways related to Autosomal Recessive Malignant Osteopetrosis according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.45 CLCN7 TCIRG1
2 10.58 TCIRG1 TNFSF11

GO Terms for Autosomal Recessive Malignant Osteopetrosis

Cellular components related to Autosomal Recessive Malignant Osteopetrosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosomal membrane GO:0005765 8.96 CLCN7 TCIRG1
2 endosome membrane GO:0010008 8.62 SNX10 TCIRG1

Biological processes related to Autosomal Recessive Malignant Osteopetrosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to leukemia inhibitory factor GO:1990830 9.32 SNX10 TNFSF11
2 osteoclast differentiation GO:0030316 9.26 SNX10 TNFSF11
3 calcium ion homeostasis GO:0055074 9.16 SNX10 TNFSF11
4 bone resorption GO:0045453 8.96 SNX10 TNFSF11
5 tooth eruption GO:0044691 8.62 SNX10 TNFSF11

Molecular functions related to Autosomal Recessive Malignant Osteopetrosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATPase binding GO:0051117 8.62 SNX10 TCIRG1

Sources for Autosomal Recessive Malignant Osteopetrosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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