MCID: RTC002
MIFTS: 51

Reticular Dysgenesis

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

Aliases & Classifications for Reticular Dysgenesis

MalaCards integrated aliases for Reticular Dysgenesis:

Name: Reticular Dysgenesis 54 12 50 24 56 71 29 13 52 42 14 69
Severe Combined Immunodeficiency with Leukopenia 50 24 56 71
De Vaal Disease 12 24 56 71
Congenital Aleukia 50 71
Aleukocytosis 12 71
Hematopoietic Hypoplasia, Generalized 71
Generalized Hematopoietic Hypoplasia 56
Congenital Aleukocytosis 56
Scid with Leukopenia 56
Devaal Disease 50
Ak2 Deficiency 56
Rdys 71
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;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
early death in the first few weeks of life


HPO:

32
reticular dysgenesis:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Rare immunological diseases


Summaries for Reticular Dysgenesis

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 33355disease definitionreticular dysgenesis is the most severe form of severe combined immunodeficiency (scid; see this term) and is characterized by bilateral sensorineural deafness and a lack of innate and adaptive immune functions leading to fatal septicemia within days after birth if not treated.epidemiologyreticular dysgenesis accounts for less than 2% of all scid cases. the annual incidence has been estimated at 1/3,000,000-1/5,000,000. both males and females are affected, and consanguinity has been noted in several families.clinical descriptionthe disease presents earlier than other forms of scid, at birth or early in the neonatal period, with signs of sepsis, failure to thrive, diarrhea, fever, recurrent infections including upper respiratory tract infections, oral candidiasis, perianal infections and abscesses, and bilateral sensorineural deafness. despite recurrent infections, no significant lymphoid or tonsillar tissue is evident. hemoglobin levels are usually within reference ranges at birth, but patients may develop anemia secondary to sepsis and chronic illness.etiologyreticular dysgenesis is characterized by profound neutropenia and t and natural killer (nk) cell lymphocytopenia, and is caused by mutations in the ak2 gene (1p34). the resulting deficiency in adenylate kinase 2 causes increased apoptosis of myeloid and lymphoid precursors. however, patients without this mutation have been observed implying an alternative cause. an imbalance of growth factor independent-1 transcriptionrepressor (gfi-1) and/or gfi-1b has been proposed.diagnostic methodsdiagnosis is based on evidence of sensorineural deafness in combination with evidence of a marked reduction of t and nk cell counts when compared to age-matched healthy controls. materno-fetal engraftment is usually present.differential diagnosisdifferential diagnosis includes all other forms of scid.antenatal diagnosisprenatal diagnosis can be performed in families where there is a family history and where the genetic mutation has been identified.genetic counselingtransmission is autosomal recessive.management and treatmentthe only curative treatment for this disease is allogenic hematopoietic stem cell transplantation.prognosiswithout treatment, patients die from septicemia within days after birth.visit the orphanet disease page for more resources. last updated: 7/1/2012

MalaCards based summary : Reticular Dysgenesis, also known as severe combined immunodeficiency with leukopenia, is related to respiratory distress syndrome in premature infants and restrictive dermopathy, lethal, and has symptoms including failure to thrive, recurrent respiratory infections and diarrhea. An important gene associated with Reticular Dysgenesis is AK2 (Adenylate Kinase 2), and among its related pathways/superpathways are Neuropathic Pain-Signaling in Dorsal Horn Neurons and AMPK Enzyme Complex Pathway. The drugs Melphalan and Cyclophosphamide have been mentioned in the context of this disorder. Affiliated tissues include myeloid, 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.

UniProtKB/Swiss-Prot : 71 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.

Wikipedia : 72 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 top 50) (show all 52)
id Related Disease Score Top Affiliating Genes
1 respiratory distress syndrome in premature infants 11.6
2 restrictive dermopathy, lethal 11.5
3 bronchopulmonary dysplasia 10.8
4 respiratory distress syndrome, infant 10.8
5 renal hypodysplasia/aplasia 2 10.8
6 refsum disease 10.8
7 renal hypodysplasia/aplasia 1 10.8
8 adult respiratory distress syndrome 10.8
9 severe combined immunodeficiency 10.6
10 retinitis 10.4
11 retinitis pigmentosa 10.2
12 rhabdomyosarcoma 10.2
13 retinal degeneration 10.2
14 choroiditis 10.0
15 cone-rod dystrophy 9.9
16 butterfly-shaped pigment dystrophy 9.8
17 embryonal rhabdomyosarcoma 9.8
18 hematopoietic stem cell transplantation 9.8
19 myelodysplastic syndrome 9.8
20 omenn syndrome 9.8
21 tuberculosis 9.7
22 retinal disease 9.7
23 childhood cerebellar astrocytic neoplasm 9.7 ADA AK2
24 atherosclerosis 9.6
25 hepatitis c 9.6
26 haemophilus influenzae 9.6
27 dysostosis 9.6
28 hepatitis c virus 9.6
29 cervicitis 9.6
30 hepatocellular carcinoma 9.6
31 hepatitis 9.6
32 oligodendroglioma 9.6
33 breast cancer 9.6
34 thrombocytopenia 9.6
35 vitelliform macular dystrophy 9.6
36 cone dystrophy 9.6
37 multidrug-resistant tuberculosis 9.6
38 acrofacial dysostosis 9.6
39 skeletal muscle cancer 9.6
40 enhanced s-cone syndrome 9.6
41 interstitial emphysema 9.6
42 muscle cancer 9.6
43 epstein syndrome 9.6
44 kidney disease 9.6
45 rett syndrome 9.6
46 ecthyma 9.6
47 geographic tongue 9.6
48 rheumatic disease 9.6
49 influenza 9.6
50 squamous cell carcinoma 9.6

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



Diseases related to Reticular Dysgenesis

Symptoms & Phenotypes for Reticular Dysgenesis

Symptoms via clinical synopsis from OMIM:

54

Hematology:
congenital agranulocytosis
leukopenia
lymphopenia
absent bone marrow myeloid elements

Immunology:
lymphoid hypoplasia
thymic hypoplasia
absent cellular immunity
absent humoral immunity


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 failure to thrive 56 32 frequent (33%) Frequent (79-30%) HP:0001508
2 recurrent respiratory infections 56 32 hallmark (90%) Very frequent (99-80%) HP:0002205
3 diarrhea 56 32 hallmark (90%) Very frequent (99-80%) HP:0002014
4 anemia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001903
5 leukopenia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001882
6 fever 56 32 frequent (33%) Frequent (79-30%) HP:0001945
7 malabsorption 56 32 frequent (33%) Frequent (79-30%) HP:0002024
8 dehydration 56 32 occasional (7.5%) Occasional (29-5%) HP:0001944
9 weight loss 56 32 frequent (33%) Frequent (79-30%) HP:0001824
10 skin rash 56 32 occasional (7.5%) Occasional (29-5%) HP:0000988
11 hearing impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0000365
12 chronic otitis media 56 32 hallmark (90%) Very frequent (99-80%) HP:0000389
13 sepsis 56 32 hallmark (90%) Very frequent (99-80%) HP:0100806
14 severe combined immunodeficiency 56 32 hallmark (90%) Very frequent (99-80%) HP:0004430
15 cellular immunodeficiency 56 32 hallmark (90%) Very frequent (99-80%) HP:0005374
16 skin ulcer 56 32 occasional (7.5%) Occasional (29-5%) HP:0200042
17 decreased antibody level in blood 56 32 hallmark (90%) Very frequent (99-80%) HP:0004313
18 abnormality of mitochondrial metabolism 56 32 hallmark (90%) Very frequent (99-80%) HP:0003287
19 aplasia/hypoplasia of the thymus 56 32 hallmark (90%) Very frequent (99-80%) HP:0010515
20 abnormality of neutrophils 56 32 hallmark (90%) Very frequent (99-80%) HP:0001874
21 congenital agranulocytosis 32 HP:0005541
22 lymphopenia 32 HP:0001888
23 absent cellular immunity 32 HP:0005354
24 abnormality of the thymus 32 HP:0000777

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 15)
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 Antiviral Agents

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Patients Treated for SCID (1968-2010) Recruiting NCT01346150
2 Natural History Study of SCID Disorders Recruiting NCT01186913
3 Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies Recruiting NCT01652092 Alemtuzumab 0.3 mg;Cyclophosphamide;Busulfan;Fludarabine phosphate 40 mg;Melphalan;Alemtuzumab 0.2 mg;Busulfan;Fludarabine phosphate 30 mg;MESNA

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
Myeloid, Bone, Bone Marrow, Thymus, Nk Cells, Skin, Neutrophil

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
Reticular dysgenesis in a preterm infant: a case report. ( 20863163 )
2010
8
Altered functional balance of Gfi-1 and Gfi-1b as an alternative cause of reticular dysgenesis? ( 19896777 )
2010
9
Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2. ( 19043417 )
2009
10
Successful cord blood transplantation in a premature and dysmature neonate of 1700 g with reticular dysgenesis. ( 17262063 )
2007
11
Successful haploidentical bone marrow transplantation in a patient with reticular dysgenesis: three-year follow-up. ( 17854878 )
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:

71
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

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 HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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