RDYS
MCID: RTC002
MIFTS: 50

Reticular Dysgenesis (RDYS) malady

Categories: Genetic diseases, Rare diseases, Blood diseases, Immune diseases

Aliases & Classifications for Reticular Dysgenesis

Aliases & Descriptions for Reticular Dysgenesis:

Name: Reticular Dysgenesis 54 12 50 24 56 66 29 13 52 42 14 69
Severe Combined Immunodeficiency with Leukopenia 50 24 56 66
De Vaal Disease 12 24 56 66
Congenital Aleukia 50 66
Aleukocytosis 12 66
Hematopoietic Hypoplasia, Generalized 66
Generalized Hematopoietic Hypoplasia 56
Congenital Aleukocytosis 56
Scid with Leukopenia 56
Devaal Disease 50
Ak2 Deficiency 56
Rdys 66
Rd 50

Characteristics:

Orphanet epidemiological data:

56
reticular dysgenesis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: early childhood;

HPO:

32
reticular dysgenesis:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Rare immunological diseases


External Ids:

OMIM 54 267500
Disease Ontology 12 DOID:0060020
NCIt 47 C27070
SNOMED-CT 64 111584000
Orphanet 56 ORPHA33355
MESH via Orphanet 43 C538361
UMLS via Orphanet 70 C0272167 C1282908
ICD10 via Orphanet 34 D81.0
MedGen 40 C0272167
UMLS 69 C0272167

Summaries for Reticular Dysgenesis

UniProtKB/Swiss-Prot : 66 Reticular dysgenesis: A fatal form of severe combined immunodeficiency, characterized by absence of granulocytes, almost complete deficiency of lymphocytes in peripheral blood, hypoplasia of the thymus and secondary lymphoid organs, and lack of innate and adaptive humoral and cellular immunity, leading to fatal septicemia within days after birth. In bone marrow of individuals with reticular dysgenesis, myeloid differentiation is blocked at the promyelocytic stage, whereas erythro- and megakaryocytic maturation is generally normal. Inheritance is autosomal recessive.

MalaCards based summary : Reticular Dysgenesis, also known as severe combined immunodeficiency with leukopenia, is related to respiratory distress syndrome in premature infants and respiratory distress syndrome, infant, and has symptoms including fever, diarrhea and failure to thrive. An important gene associated with Reticular Dysgenesis is AK2 (Adenylate Kinase 2), and among its related pathways/superpathways are Purine metabolism (KEGG) and Neuropathic Pain-Signaling in Dorsal Horn Neurons. The drugs Melphalan and Cyclophosphamide have been mentioned in the context of this disorder. Affiliated tissues include thymus, bone and bone marrow, and related phenotype is Decreased viability.

Disease Ontology : 12 A severe combined immunodeficiency that is the most severe form of SCID and has material basis in mutations in the gene encoding mitochondrial adenylate kinase 2. It is characterized by congenital agranulocytosis, lymphopenia, and lymphoid and thymic hypoplasia with absent cellular and humoral immunity functions.

Wikipedia : 71 Reticular dysgenesis (RD) is a rare, inherited autosomal recessive disease that results in... more...

Description from OMIM: 267500

Related Diseases for Reticular Dysgenesis

Diseases related to Reticular Dysgenesis via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 49)
id Related Disease Score Top Affiliating Genes
1 respiratory distress syndrome in premature infants 11.6
2 respiratory distress syndrome, infant 10.9
3 bronchopulmonary dysplasia 10.8
4 renal hypodysplasia/aplasia 2 10.8
5 renal hypodysplasia/aplasia 1 10.8
6 adult respiratory distress syndrome 10.8
7 restrictive dermopathy, lethal 10.8
8 refsum disease 10.8
9 retinitis 10.4
10 retinitis pigmentosa 10.2
11 rhabdomyosarcoma 10.2
12 retinal degeneration 10.2
13 severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 10.2
14 choroiditis 10.0
15 single ventricular heart 9.9 ADA AK2
16 cone-rod dystrophy 9.9
17 butterfly-shaped pigment dystrophy 9.8
18 embryonal rhabdomyosarcoma 9.8
19 hematopoietic stem cell transplantation 9.8
20 myelodysplastic syndrome 9.8
21 severe combined immunodeficiency 9.8
22 omenn syndrome 9.8
23 tuberculosis 9.7
24 retinal disease 9.7
25 hepatitis b 9.7 ADA AK1
26 epstein syndrome 9.6
27 influenza 9.6
28 rett syndrome 9.6
29 ecthyma 9.6
30 polycystic kidney disease 9.6
31 geographic tongue 9.6
32 haemophilus influenzae 9.6
33 rheumatic disease 9.6
34 squamous cell carcinoma 9.6
35 atherosclerosis 9.6
36 hepatitis c 9.6
37 dysostosis 9.6
38 hepatocellular carcinoma 9.6
39 oligodendroglioma 9.6
40 hepatitis 9.6
41 hepatitis c virus 9.6
42 thrombocytopenia 9.6
43 vitelliform macular dystrophy 9.6
44 multidrug-resistant tuberculosis 9.6
45 cone dystrophy 9.6
46 kidney disease 9.6
47 acrofacial dysostosis 9.6
48 enhanced s-cone syndrome 9.6
49 interstitial emphysema 9.6

Graphical network of the top 20 diseases related to Reticular Dysgenesis:



Diseases related to Reticular Dysgenesis

Symptoms & Phenotypes for Reticular Dysgenesis

Symptoms by clinical synopsis from OMIM:

267500

Clinical features from OMIM:

267500

Human phenotypes related to Reticular Dysgenesis:

56 32 (show all 24)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 fever 56 32 Frequent (79-30%) HP:0001945
2 diarrhea 56 32 Very frequent (99-80%) HP:0002014
3 failure to thrive 56 32 Frequent (79-30%) HP:0001508
4 hearing impairment 56 32 Very frequent (99-80%) HP:0000365
5 chronic otitis media 56 32 Very frequent (99-80%) HP:0000389
6 recurrent respiratory infections 56 32 Very frequent (99-80%) HP:0002205
7 malabsorption 56 32 Frequent (79-30%) HP:0002024
8 dehydration 56 32 Occasional (29-5%) HP:0001944
9 anemia 56 32 Very frequent (99-80%) HP:0001903
10 weight loss 56 32 Frequent (79-30%) HP:0001824
11 skin ulcer 56 32 Occasional (29-5%) HP:0200042
12 decreased antibody level in blood 56 32 Very frequent (99-80%) HP:0004313
13 abnormality of mitochondrial metabolism 56 32 Very frequent (99-80%) HP:0003287
14 cellular immunodeficiency 56 32 Very frequent (99-80%) HP:0005374
15 aplasia/hypoplasia of the thymus 56 32 Very frequent (99-80%) HP:0010515
16 skin rash 56 32 Occasional (29-5%) HP:0000988
17 sepsis 56 32 Very frequent (99-80%) HP:0100806
18 abnormality of neutrophils 56 32 Very frequent (99-80%) HP:0001874
19 leukopenia 56 32 Very frequent (99-80%) HP:0001882
20 severe combined immunodeficiency 56 32 Very frequent (99-80%) HP:0004430
21 lymphopenia 32 HP:0001888
22 abnormality of the thymus 32 HP:0000777
23 congenital agranulocytosis 32 HP:0005541
24 absent cellular immunity 32 HP:0005354

GenomeRNAi Phenotypes related to Reticular Dysgenesis according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00107-A-1 9.77 AK2 AK1
2 Decreased viability GR00221-A-1 9.77 AK7
3 Decreased viability GR00221-A-3 9.77 AK7
4 Decreased viability GR00221-A-4 9.77 AK7 AK2
5 Decreased viability GR00301-A 9.77 AK2
6 Decreased viability GR00342-S-1 9.77 AK7
7 Decreased viability GR00342-S-2 9.77 AK2 AK7
8 Decreased viability GR00342-S-3 9.77 AK7 AK2

Drugs & Therapeutics for Reticular Dysgenesis

Drugs for Reticular Dysgenesis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 16)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Melphalan Approved 148-82-3 4053 460612
2
Cyclophosphamide Approved, Investigational 50-18-0, 6055-19-2 2907
3
Fludarabine Approved 21679-14-1, 75607-67-9 30751
4
Vidarabine Approved 24356-66-9 32326 21704
5
Busulfan Approved, Investigational 55-98-1 2478
6
Mesna Approved 3375-50-6 598
7
alemtuzumab Approved, Investigational 216503-57-0
8 Alkylating Agents
9 Anti-Infective Agents
10 Immunosuppressive Agents
11 Protective Agents
12 Antimetabolites
13 Antimetabolites, Antineoplastic
14 Antirheumatic Agents
15 Antineoplastic Agents, Alkylating
16 Antiviral Agents

Interventional clinical trials:


id Name Status NCT ID Phase
1 Retinal Neurodegenerative Signs in Alzheimer's Diseases Unknown status NCT01555827
2 Patients Treated for SCID (1968-2010) Recruiting NCT01346150
3 Natural History Study of SCID Disorders Recruiting NCT01186913
4 Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies Recruiting NCT01652092

Search NIH Clinical Center for Reticular Dysgenesis

Cochrane evidence based reviews: reticular dysgenesis

Genetic Tests for Reticular Dysgenesis

Genetic tests related to Reticular Dysgenesis:

id Genetic test Affiliating Genes
1 Reticular Dysgenesis 29 24 AK2

Anatomical Context for Reticular Dysgenesis

MalaCards organs/tissues related to Reticular Dysgenesis:

39
Thymus, Bone, Bone Marrow, Myeloid, Skin, Neutrophil, B Cells

Publications for Reticular Dysgenesis

Articles related to Reticular Dysgenesis:

(show all 23)
id Title Authors Year
1
Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome. ( 28331055 )
2017
2
Postpartum HLA-Matched Bone Marrow Donation from Mother to Neonate for Reticular Dysgenesis. ( 27913909 )
2017
3
Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress. ( 26150473 )
2015
4
Skeletal abnormalities and successful hematopoietic stem cell transplantation in patients with reticular dysgenesis. ( 23763981 )
2013
5
First reported case of Omenn syndrome in a patient with reticular dysgenesis. ( 23014587 )
2013
6
Occurrence of myelodysplastic syndrome in 2 patients with reticular dysgenesis. ( 21458044 )
2011
7
Altered functional balance of Gfi-1 and Gfi-1b as an alternative cause of reticular dysgenesis? ( 19896777 )
2010
8
Reticular dysgenesis in a preterm infant: a case report. ( 20863163 )
2010
9
Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2. ( 19043417 )
2009
10
Successful haploidentical bone marrow transplantation in a patient with reticular dysgenesis: three-year follow-up. ( 17854878 )
2007
11
Successful cord blood transplantation in a premature and dysmature neonate of 1700 g with reticular dysgenesis. ( 17262063 )
2007
12
Reticular dysgenesis: HLA non-identical bone marrow transplants in a series of 10 patients. ( 12040473 )
2002
13
Langerhans cell deficiency in reticular dysgenesis. ( 10891430 )
2000
14
Association of reticular dysgenesis (thymic alymphoplasia and congenital aleukocytosis) with bilateral sensorineural deafness. ( 10484810 )
1999
15
B cells and monocytes are not developmentally affected in a case of reticular dysgenesis. ( 9409641 )
1997
16
Haploidentical bone marrow transplants for two patients with reticular dysgenesis. ( 8807131 )
1996
17
Use of recombinant human granulocyte-macrophage colony stimulating factor in an infant with reticular dysgenesis. ( 8181497 )
1994
18
Effect of recombinant human granulocyte colony-stimulating factor in reticular dysgenesis. ( 7689877 )
1993
19
Use of recombinant human granulocyte colony stimulating factor in reticular dysgenesis. ( 1381605 )
1992
20
Severe congenital leukopenia (reticular dysgenesis). Immunologic and morphologic characterizations of leukocytes. ( 3875278 )
1985
21
Successful bone-marrow transplantation for reticular dysgenesis. ( 6132037 )
1983
22
Reticular dysgenesis: report of two brothers. ( 535190 )
1979
23
Severe combined immunodeficiency with leukopenia (reticular dysgenesis) in siblings: immunologic and histopathologic findings. ( 956962 )
1976

Variations for Reticular Dysgenesis

UniProtKB/Swiss-Prot genetic disease variations for Reticular Dysgenesis:

66
id Symbol AA change Variation ID SNP ID
1 AK2 p.Arg103Trp VAR_054630 rs267606648
2 AK2 p.Asp165Gly VAR_054631 rs267606643

ClinVar genetic disease variations for Reticular Dysgenesis:

6 (show all 13)
id Gene Variation Type Significance SNP ID Assembly Location
1 AK2 AK2, 5,038-BP DEL deletion Pathogenic
2 AK2 NM_013411.4(AK2): c.118delT (p.Cys40Valfs) deletion Pathogenic rs387906581 GRCh37 Chromosome 1, 33490144: 33490144
3 AK2 NM_013411.4(AK2): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs137853206 GRCh37 Chromosome 1, 33502429: 33502429
4 AK2 AK2, 331, G-A, -1 single nucleotide variant Pathogenic
5 AK2 AK2, 1-BP DEL, 453C deletion Pathogenic
6 AK2 AK2, 498, G-A, +1 single nucleotide variant Pathogenic
7 AK2 NM_013411.4(AK2): c.494A> G (p.Asp165Gly) single nucleotide variant Pathogenic rs267606643 GRCh37 Chromosome 1, 33480127: 33480127
8 AK2 NM_013411.4(AK2): c.548T> A (p.Leu183Ter) single nucleotide variant Pathogenic rs267606644 GRCh37 Chromosome 1, 33478954: 33478954
9 AK2 NM_013411.4(AK2): c.556C> T (p.Arg186Cys) single nucleotide variant Pathogenic rs267606645 GRCh37 Chromosome 1, 33478946: 33478946
10 AK2 AK2, EX2 DEL deletion Pathogenic
11 AK2 NM_013411.4(AK2): c.307C> T (p.Arg103Trp) single nucleotide variant Pathogenic rs267606648 GRCh37 Chromosome 1, 33487217: 33487217
12 AK2 NM_001625.3(AK2): c.697A> T (p.Lys233Ter) single nucleotide variant Pathogenic rs267606646 GRCh37 Chromosome 1, 33478805: 33478805
13 AK2 NM_013411.4(AK2): c.25G> T (p.Glu9Ter) single nucleotide variant Pathogenic rs267606647 GRCh37 Chromosome 1, 33502405: 33502405

Expression for Reticular Dysgenesis

Search GEO for disease gene expression data for Reticular Dysgenesis.

Pathways for Reticular Dysgenesis

Pathways related to Reticular Dysgenesis according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.2 ADA AK1 AK2 AK7
2
Show member pathways
12.17 AK1 AK2 AK7
3
Show member pathways
11.9 ADA AK1 AK2 AK7
4
Show member pathways
11.78 AK1 AK2 AK7
5
Show member pathways
11.37 ADA AK1 AK2 AK7
6 10.73 AK1 AK2 AK7
7 10 AK1 AK2 AK7

GO Terms for Reticular Dysgenesis

Cellular components related to Reticular Dysgenesis according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 sperm flagellum GO:0036126 8.62 AK1 AK2

Biological processes related to Reticular Dysgenesis according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 9.63 AK1 AK2 AK7
2 ATP metabolic process GO:0046034 9.43 AK1 AK2
3 nucleoside diphosphate phosphorylation GO:0006165 9.4 AK1 AK7
4 nucleoside triphosphate biosynthetic process GO:0009142 9.37 AK1 AK7
5 nucleobase-containing compound metabolic process GO:0006139 9.33 AK1 AK2 AK7
6 AMP metabolic process GO:0046033 9.32 AK1 AK2
7 ADP biosynthetic process GO:0006172 9.26 AK1 AK2
8 nucleobase-containing small molecule interconversion GO:0015949 9.13 AK1 AK2 AK7
9 nucleotide phosphorylation GO:0046939 8.8 AK1 AK2 AK7

Molecular functions related to Reticular Dysgenesis according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 kinase activity GO:0016301 9.43 AK1 AK2 AK7
2 nucleoside diphosphate kinase activity GO:0004550 9.16 AK1 AK7
3 adenylate kinase activity GO:0004017 9.13 AK1 AK2 AK7
4 nucleobase-containing compound kinase activity GO:0019205 8.8 AK1 AK2 AK7

Sources for Reticular Dysgenesis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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