MCID: RTC002
MIFTS: 53

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 53 12 49 55 71 36 28 13 51 41 14 69
Severe Combined Immunodeficiency with Leukopenia 53 49 55 71
De Vaal Disease 53 12 55 71
Congenital Aleukia 53 49 71
Aleukocytosis 53 12 71
Hematopoietic Hypoplasia, Generalized 53 71
Generalized Hematopoietic Hypoplasia 55
Congenital Aleukocytosis 55
Reticular Dysgenesia 53
Scid with Leukopenia 55
Devaal Disease 49
Ak2 Deficiency 55
Rdys 71
Rd 49

Characteristics:

Orphanet epidemiological data:

55
reticular dysgenesis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
early death in the first few weeks of life


HPO:

31
reticular dysgenesis:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Rare immunological diseases


External Ids:

OMIM 53 267500
Disease Ontology 12 DOID:0060020
NCIt 46 C27070
SNOMED-CT 64 111584000
Orphanet 55 ORPHA33355
MESH via Orphanet 42 C538361
UMLS via Orphanet 70 C0272167 C1282908
ICD10 via Orphanet 33 D81.0
MedGen 39 C0272167
KEGG 36 H01128
UMLS 69 C0272167

Summaries for Reticular Dysgenesis

NIH Rare Diseases : 49 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 severe combined immunodeficiency and combined immunodeficiency, x-linked, 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 and Pyrimidine metabolism (KEGG). The drugs alemtuzumab and Busulfan have been mentioned in the context of this disorder. Affiliated tissues include myeloid, bone and bone marrow, and related phenotypes are Decreased viability and 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 65)
# Related Disease Score Top Affiliating Genes
1 severe combined immunodeficiency 30.5 ADA AK2
2 combined immunodeficiency, x-linked 29.3 ADA AK2
3 respiratory distress syndrome in premature infants 11.8
4 restrictive dermopathy, lethal 11.6
5 immunoerythromyeloid hypoplasia 11.5
6 radin blood group antigen 11.4
7 newborn respiratory distress syndrome 11.1
8 respiratory distress syndrome, infant 11.0
9 renal hypodysplasia/aplasia 1 10.9
10 refsum disease, classic 10.9
11 renal hypodysplasia/aplasia 2 10.9
12 adult respiratory distress syndrome 10.9
13 bronchopulmonary dysplasia 10.9
14 retinitis 10.5
15 retinitis pigmentosa 10.3
16 leber congenital amaurosis 4 10.3
17 rhabdomyosarcoma 10.3
18 retinal degeneration 10.3
19 choroiditis 10.1
20 cone-rod dystrophy 2 10.0
21 embryonal rhabdomyosarcoma 9.9
22 butterfly-shaped pigment dystrophy 9.9
23 branchiootic syndrome 1 9.9
24 omenn syndrome 9.9
25 myelodysplastic syndrome 9.9
26 hematopoietic stem cell transplantation 9.9
27 macular degeneration, age-related, 1 9.8
28 mycobacterium tuberculosis 1 9.8
29 retinal disease 9.8
30 breast cancer 9.7
31 hepatocellular carcinoma 9.7
32 epstein syndrome 9.7
33 stargardt disease 1 9.7
34 polycystic kidney disease 4 with or without hepatic disease 9.7
35 enhanced s-cone syndrome 9.7
36 squamous cell carcinoma, head and neck 9.7
37 retinitis pigmentosa 6 9.7
38 rett syndrome 9.7
39 aging 9.7
40 cervical cancer 9.7
41 vitiligo-associated multiple autoimmune disease susceptibility 1 9.7
42 hepatitis c virus 9.7
43 polycystic kidney disease 5 9.7
44 hepatitis 9.7
45 thrombocytopenia 9.7
46 vitelliform macular dystrophy 9.7
47 cone dystrophy 9.7
48 acrofacial dysostosis 9.7
49 interstitial emphysema 9.7
50 hydronephrosis 9.7

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:

53
Hematology:
lymphopenia
leukopenia
congenital agranulocytosis
absent bone marrow myeloid elements

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


Clinical features from OMIM:

267500

Human phenotypes related to Reticular Dysgenesis:

55 31 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 fever 55 31 frequent (33%) Frequent (79-30%) HP:0001945
2 diarrhea 55 31 hallmark (90%) Very frequent (99-80%) HP:0002014
3 failure to thrive 55 31 frequent (33%) Frequent (79-30%) HP:0001508
4 hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000365
5 chronic otitis media 55 31 hallmark (90%) Very frequent (99-80%) HP:0000389
6 recurrent respiratory infections 55 31 hallmark (90%) Very frequent (99-80%) HP:0002205
7 malabsorption 55 31 frequent (33%) Frequent (79-30%) HP:0002024
8 dehydration 55 31 occasional (7.5%) Occasional (29-5%) HP:0001944
9 anemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001903
10 weight loss 55 31 frequent (33%) Frequent (79-30%) HP:0001824
11 skin ulcer 55 31 occasional (7.5%) Occasional (29-5%) HP:0200042
12 decreased antibody level in blood 55 31 hallmark (90%) Very frequent (99-80%) HP:0004313
13 abnormality of mitochondrial metabolism 55 31 hallmark (90%) Very frequent (99-80%) HP:0003287
14 cellular immunodeficiency 55 31 hallmark (90%) Very frequent (99-80%) HP:0005374
15 aplasia/hypoplasia of the thymus 55 31 hallmark (90%) Very frequent (99-80%) HP:0010515
16 skin rash 55 31 occasional (7.5%) Occasional (29-5%) HP:0000988
17 sepsis 55 31 hallmark (90%) Very frequent (99-80%) HP:0100806
18 abnormality of neutrophils 55 31 hallmark (90%) Very frequent (99-80%) HP:0001874
19 leukopenia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001882
20 severe combined immunodeficiency 55 31 hallmark (90%) Very frequent (99-80%) HP:0004430
21 lymphopenia 31 HP:0001888
22 hypoplasia of the thymus 31 HP:0000778
23 impaired t cell function 31 HP:0005435
24 congenital agranulocytosis 31 HP:0005541
25 combined immunodeficiency 31 HP:0005387
26 lack of t cell function 31 HP:0005354

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

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00107-A-1 9.77 AK1 AK2
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 AK2 AK7
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 AK7 AK2
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)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
alemtuzumab Approved, Investigational 216503-57-0
2
Busulfan Approved, Investigational 55-98-1 2478
3
Cyclophosphamide Approved, Investigational 50-18-0, 6055-19-2 2907
4
Fludarabine Approved 21679-14-1, 75607-67-9 30751
5
Melphalan Approved 148-82-3 460612 4053
6
Mesna Approved, Investigational 3375-50-6 598
7
Vidarabine Approved, Investigational 24356-66-9 21704 32326
8 Alkylating Agents
9 Anti-Infective Agents
10 Antimetabolites
11 Antimetabolites, Antineoplastic
12 Antirheumatic Agents
13 Antiviral Agents
14 Immunosuppressive Agents
15 Protective Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Patients Treated for SCID (1968-Present) 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:

# Genetic test Affiliating Genes
1 Reticular Dysgenesis 28 AK2

Anatomical Context for Reticular Dysgenesis

MalaCards organs/tissues related to Reticular Dysgenesis:

38
Myeloid, Bone, Bone Marrow, Thymus, Nk Cells, Skin, T Cells

Publications for Reticular Dysgenesis

Articles related to Reticular Dysgenesis:

(show all 24)
# Title Authors Year
1
Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome. ( 28331055 )
2017
2
Recent advances in understanding the pathogenesis and management of reticular dysgenesis. ( 29270983 )
2017
3
Postpartum HLA-Matched Bone Marrow Donation from Mother to Neonate for Reticular Dysgenesis. ( 27913909 )
2017
4
Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress. ( 26150473 )
2015
5
First reported case of Omenn syndrome in a patient with reticular dysgenesis. ( 23014587 )
2013
6
Skeletal abnormalities and successful hematopoietic stem cell transplantation in patients with reticular dysgenesis. ( 23763981 )
2013
7
Occurrence of myelodysplastic syndrome in 2 patients with reticular dysgenesis. ( 21458044 )
2011
8
Altered functional balance of Gfi-1 and Gfi-1b as an alternative cause of reticular dysgenesis? ( 19896777 )
2010
9
Reticular dysgenesis in a preterm infant: a case report. ( 20863163 )
2010
10
Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2. ( 19043417 )
2009
11
Successful haploidentical bone marrow transplantation in a patient with reticular dysgenesis: three-year follow-up. ( 17854878 )
2007
12
Successful cord blood transplantation in a premature and dysmature neonate of 1700 g with reticular dysgenesis. ( 17262063 )
2007
13
Reticular dysgenesis: HLA non-identical bone marrow transplants in a series of 10 patients. ( 12040473 )
2002
14
Langerhans cell deficiency in reticular dysgenesis. ( 10891430 )
2000
15
Association of reticular dysgenesis (thymic alymphoplasia and congenital aleukocytosis) with bilateral sensorineural deafness. ( 10484810 )
1999
16
B cells and monocytes are not developmentally affected in a case of reticular dysgenesis. ( 9409641 )
1997
17
Haploidentical bone marrow transplants for two patients with reticular dysgenesis. ( 8807131 )
1996
18
Use of recombinant human granulocyte-macrophage colony stimulating factor in an infant with reticular dysgenesis. ( 8181497 )
1994
19
Effect of recombinant human granulocyte colony-stimulating factor in reticular dysgenesis. ( 7689877 )
1993
20
Use of recombinant human granulocyte colony stimulating factor in reticular dysgenesis. ( 1381605 )
1992
21
Severe congenital leukopenia (reticular dysgenesis). Immunologic and morphologic characterizations of leukocytes. ( 3875278 )
1985
22
Successful bone-marrow transplantation for reticular dysgenesis. ( 6132037 )
1983
23
Reticular dysgenesis: report of two brothers. ( 535190 )
1979
24
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
# 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)
# Gene Variation Type Significance SNP ID Assembly Location
1 AK2 NM_013411.4(AK2): c.25G> T (p.Glu9Ter) single nucleotide variant Pathogenic rs267606647 GRCh37 Chromosome 1, 33502405: 33502405
2 AK2 NM_013411.4(AK2): c.636_*2601del deletion Pathogenic
3 AK2 NM_013411.4(AK2): c.118delT (p.Cys40Valfs) deletion Pathogenic rs387906581 GRCh37 Chromosome 1, 33490144: 33490144
4 AK2 NM_013411.4(AK2): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs137853206 GRCh37 Chromosome 1, 33502429: 33502429
5 AK2 AK2, 331, G-A, -1 single nucleotide variant Pathogenic
6 AK2 NM_013411.4(AK2): c.453delC (p.Tyr152Thrfs) deletion Pathogenic GRCh38 Chromosome 1, 33014567: 33014567
7 AK2 AK2, 498, G-A, +1 single nucleotide variant Pathogenic
8 AK2 NM_013411.4(AK2): c.494A> G (p.Asp165Gly) single nucleotide variant Pathogenic rs267606643 GRCh37 Chromosome 1, 33480127: 33480127
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.523delC (p.Arg175Aspfs) deletion Pathogenic GRCh37 Chromosome 1, 33478979: 33478979

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 KEGG:

36
# Name Kegg Source Accession
1 Purine metabolism hsa00230

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.19 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:

# 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:

# 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 nucleotide phosphorylation GO:0046939 9.37 AK1 AK2
5 nucleoside triphosphate biosynthetic process GO:0009142 9.32 AK1 AK7
6 AMP metabolic process GO:0046033 9.26 AK1 AK2
7 ADP biosynthetic process GO:0006172 9.16 AK1 AK2
8 nucleobase-containing compound metabolic process GO:0006139 9.13 AK1 AK2 AK7
9 nucleobase-containing small molecule interconversion GO:0015949 8.8 AK1 AK2 AK7

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

# 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
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....