MCID: ATS282
MIFTS: 46

Autosomal Recessive Malignant Osteopetrosis

Categories: Blood diseases, Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Liver 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 alemtuzumab and Busulfan 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 29.0 CLCN7 SNX10 TCIRG1 TNFSF11
2 osteopetrosis, autosomal recessive 5 12.0
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 9.8 CLCN7 TCIRG1
15 osteopetrosis, autosomal recessive 2 9.7 CLCN7 TNFSF11
16 bone disease 9.5 CLCN7 TNFSF11
17 osteopetrosis, autosomal dominant 2 9.5 CLCN7 TCIRG1 TNFSF11
18 endosteal hyperostosis, autosomal dominant 9.5 CLCN7 TCIRG1 TNFSF11
19 bone remodeling disease 9.4 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:

60 33 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0000256
2 abnormality of epiphysis morphology 60 33 hallmark (90%) Very frequent (99-80%) HP:0005930
3 hydrocephalus 60 33 hallmark (90%) Very frequent (99-80%) HP:0000238
4 nystagmus 60 33 hallmark (90%) Very frequent (99-80%) HP:0000639
5 tremor 60 33 hallmark (90%) Very frequent (99-80%) HP:0001337
6 hearing impairment 60 33 hallmark (90%) Very frequent (99-80%) HP:0000365
7 splenomegaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0001744
8 recurrent respiratory infections 60 33 hallmark (90%) Very frequent (99-80%) HP:0002205
9 hepatomegaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0002240
10 bowing of the long bones 60 33 hallmark (90%) Very frequent (99-80%) HP:0006487
11 visual impairment 60 33 hallmark (90%) Very frequent (99-80%) HP:0000505
12 abnormality of visual evoked potentials 60 33 hallmark (90%) Very frequent (99-80%) HP:0000649
13 anemia 60 33 hallmark (90%) Very frequent (99-80%) HP:0001903
14 pallor 60 33 hallmark (90%) Very frequent (99-80%) HP:0000980
15 abnormal blistering of the skin 60 33 hallmark (90%) Very frequent (99-80%) HP:0008066
16 abnormality of the metaphysis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000944
17 delayed eruption of teeth 60 33 hallmark (90%) Very frequent (99-80%) HP:0000684
18 narrow chest 60 33 hallmark (90%) Very frequent (99-80%) HP:0000774
19 reduced bone mineral density 60 33 hallmark (90%) Very frequent (99-80%) HP:0004349
20 growth delay 60 33 hallmark (90%) Very frequent (99-80%) HP:0001510
21 abnormality of temperature regulation 60 33 hallmark (90%) Very frequent (99-80%) HP:0004370
22 abnormality of the ribs 60 33 hallmark (90%) Very frequent (99-80%) HP:0000772
23 recurrent fractures 60 33 hallmark (90%) Very frequent (99-80%) HP:0002757
24 otitis media 60 33 hallmark (90%) Very frequent (99-80%) HP:0000388
25 bone pain 60 33 hallmark (90%) Very frequent (99-80%) HP:0002653
26 craniosynostosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0001363
27 lymphadenopathy 60 33 hallmark (90%) Very frequent (99-80%) HP:0002716
28 osteopetrosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0011002
29 optic nerve compression 60 33 hallmark (90%) Very frequent (99-80%) HP:0007807
30 chronic rhinitis 60 33 hallmark (90%) Very frequent (99-80%) HP:0002257
31 abnormality of hair texture 60 33 hallmark (90%) Very frequent (99-80%) HP:0010719
32 premature loss of primary teeth 60 33 hallmark (90%) Very frequent (99-80%) HP:0006323
33 opsoclonus 60 33 hallmark (90%) Very frequent (99-80%) HP:0010543
34 hypophosphatemia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002148
35 cranial nerve paralysis 60 33 occasional (7.5%) Occasional (29-5%) HP:0006824
36 pulmonary arterial hypertension 60 33 occasional (7.5%) Occasional (29-5%) HP:0002092
37 apnea 60 33 occasional (7.5%) Occasional (29-5%) HP:0002104
38 hypocalcemia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002901
39 bruising susceptibility 60 33 occasional (7.5%) Occasional (29-5%) HP:0000978
40 pulmonary artery stenosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0004415
41 abnormal pulmonary valve morphology 33 occasional (7.5%) HP:0001641
42 abnormality of metabolism/homeostasis 60 Very frequent (99-80%)
43 abnormality of movement 60 Very frequent (99-80%)
44 abnormality of the pulmonary valve 60 Occasional (29-5%)

MGI Mouse Phenotypes related to Autosomal Recessive Malignant Osteopetrosis:

47
# 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 30)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
alemtuzumab Approved, Investigational Phase 2, Phase 3 216503-57-0
2
Busulfan Approved, Investigational Phase 2, Phase 3 55-98-1 2478
3
Vidarabine Approved, Investigational Phase 2, Phase 3 24356-66-9 21704 32326
4
Cyclophosphamide Approved, Investigational Phase 2, Phase 3 50-18-0, 6055-19-2 2907
5
Fludarabine Approved Phase 2, Phase 3,Phase 3 75607-67-9, 21679-14-1 30751
6 Immunosuppressive Agents Phase 2, Phase 3
7 Antiviral Agents Phase 2, Phase 3
8 Antineoplastic Agents, Alkylating Phase 2, Phase 3
9 Antimetabolites, Antineoplastic Phase 2, Phase 3
10 Antineoplastic Agents, Immunological Phase 2, Phase 3
11 Antirheumatic Agents Phase 2, Phase 3
12 Immunologic Factors Phase 2, Phase 3
13 Alkylating Agents Phase 2, Phase 3
14 Anti-Infective Agents Phase 2, Phase 3
15 Antimetabolites Phase 2, Phase 3
16
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
17
Acetylcysteine Approved, Investigational Phase 2 616-91-1 12035
18
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
19
rituximab Approved Phase 2 174722-31-7 10201696
20
Tocopherol Approved, Investigational Phase 2 1406-66-2 14986
21
Clofarabine Approved, Investigational Phase 2 123318-82-1 119182
22
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
23 Tocotrienol Investigational Phase 2 6829-55-6
24 Tocopherols Phase 2
25 Thioctic Acid Phase 2
26 Vitamins Phase 2
27 Tocotrienols Phase 2
28 Antilymphocyte Serum Phase 2
29 N-monoacetylcystine Phase 2
30 Alpha-lipoic 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:

42
Bone, Skin, Eye, Bone Marrow, T Cells, Liver

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 )
2018
4
[Analysis of TCIRG1 gene mutation in a Chinese family affected with infantile malignant osteopetrosis]. ( 28604959 )
2017
5
Improved Outcomes of Hematopoietic Stem Cell Transplantation in Patients With Infantile Malignant Osteopetrosis Using Fludarabine-Based Conditioning. ( 26485304 )
2016
6
Identification and Characterization of Mutations in the CLCN7 Gene in a Taiwanese Patient with Infantile Malignant Osteopetrosis. ( 26365571 )
2016
7
A novel mutation and a known mutation in the CLCN7 gene associated with relatively stable infantile malignant osteopetrosis in a Chinese patient. ( 26477479 )
2016
8
Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy. ( 27541021 )
2016
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 )
2014
12
Infantile malignant osteopetrosis. ( 23721911 )
2013
13
Lentiviral gene transfer of TCIRG1 into peripheral blood CD34(+) cells restores osteoclast function in infantile malignant osteopetrosis. ( 23907031 )
2013
14
Infantile malignant osteopetrosis: report of 2 cases with osteomyelitis of the jaws. ( 22828766 )
2012
15
Infantile malignant osteopetrosis: a rare cause of neonatal hypocalcemia. ( 23329773 )
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
Novel mutations in the a3 subunit of vacuolar H(+)-adenosine triphosphatase in a Japanese patient with infantile malignant osteopetrosis. ( 11856654 )
2002
28
Infantile Malignant Osteopetrosis: Delay in Diagnosis Eliminates Chance of Cure. ( 27264978 )
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 EFO
18 ExPASy
20 FMA
29 GO
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31 HGMD
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35 ICD10 via Orphanet
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59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
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74 UMLS
75 UMLS via Orphanet
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