AIADK
MCID: ATN014
MIFTS: 38

Autoinflammation with Arthritis and Dyskeratosis (AIADK)

Categories: Genetic diseases, Skin diseases

Aliases & Classifications for Autoinflammation with Arthritis and Dyskeratosis

MalaCards integrated aliases for Autoinflammation with Arthritis and Dyskeratosis:

Name: Autoinflammation with Arthritis and Dyskeratosis 57 74 6
Hereditary Autoinflammatory Diseases 44 72
Aiadk 57 74

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
variable features present
based on report of 2 double first cousins and 1 unrelated sporadic heterozygote (patient a)


HPO:

32
autoinflammation with arthritis and dyskeratosis:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 617388
UMLS 72 C0751422

Summaries for Autoinflammation with Arthritis and Dyskeratosis

OMIM : 57 Autoinflammation with arthritis and dyskeratosis is characterized by recurrent fever, widespread skin dyskeratosis, arthritis, elevated biologic markers of inflammation, and mild autoimmunity with a high transitional B-cell level (summary by Grandemange et al., 2016). (617388)

MalaCards based summary : Autoinflammation with Arthritis and Dyskeratosis, also known as hereditary autoinflammatory diseases, is related to familial cold autoinflammatory syndrome and familial mediterranean fever. An important gene associated with Autoinflammation with Arthritis and Dyskeratosis is NLRP1 (NLR Family Pyrin Domain Containing 1), and among its related pathways/superpathways are Toll-like Receptor Signaling Pathway and RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways. The drugs Colchicine and Tubulin Modulators have been mentioned in the context of this disorder. Affiliated tissues include skin, b cells and thyroid, and related phenotypes are failure to thrive and splenomegaly

UniProtKB/Swiss-Prot : 74 Autoinflammation with arthritis and dyskeratosis: A disorder characterized by recurrent fever, diffuse skin dyskeratosis, autoinflammation, autoimmunity, arthritis and high transitional B-cell level. Inheritance can be autosomal dominant or autosomal recessive.

Related Diseases for Autoinflammation with Arthritis and Dyskeratosis

Graphical network of the top 20 diseases related to Autoinflammation with Arthritis and Dyskeratosis:



Diseases related to Autoinflammation with Arthritis and Dyskeratosis

Symptoms & Phenotypes for Autoinflammation with Arthritis and Dyskeratosis

Human phenotypes related to Autoinflammation with Arthritis and Dyskeratosis:

32 (show all 17)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 splenomegaly 32 HP:0001744
3 photophobia 32 HP:0000613
4 hyperkeratosis 32 HP:0000962
5 dry skin 32 HP:0000958
6 growth delay 32 HP:0001510
7 thyroiditis 32 HP:0100646
8 keratoconjunctivitis sicca 32 HP:0001097
9 corneal neovascularization 32 HP:0011496
10 uveitis 32 HP:0000554
11 autoimmune hemolytic anemia 32 HP:0001890
12 epidermal acanthosis 32 HP:0025092
13 antinuclear antibody positivity 32 HP:0003493
14 hypereosinophilia 32 HP:0032061
15 polyarticular arthritis 32 HP:0005764
16 punctate keratitis 32 HP:0011859
17 increased circulating iga level 32 HP:0003261

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive
growth retardation, moderate

Skin Nails Hair Skin Histology:
hyperkeratosis
acanthosis
prominent granular cell layer
mild papillomatosis
dyskeratotic eosinophilic cells throughout all layers
more
Laboratory Abnormalities:
hypereosinophilia
persistently elevated c-reactive protein (crp)
reduced levels of vitamin a
reduced levels of retinal-binding protein
reduced levels of vitamin c

Head And Neck Neck:
thyroiditis (patient a)

Respiratory Airways:
subglottic edema (patient a)

Abdomen Spleen:
splenomegaly (requiring splenectomy, patient a)

Skeletal Hands:
arthritis of the hands

Skin Nails Hair Hair:
hair casts

Hematology:
hemolytic anemia, autoimmune (patient a)

Head And Neck Eyes:
photophobia
corneal neovascularization
uveitis
punctate keratitis
corneal dyskeratosis
more
Immunology:
hypereosinophilia
antinuclear antibodies
elevated iga
elevated ige
chronic candidiasis (patient a)
more
Skin Nails Hair Skin:
xerosis
impaired sweating
widespread follicular hyperkeratosis
filiform hyperkeratosis
brownish-purple pigmented macules in areas of hyperkeratosis
more
Respiratory Larynx:
verrucous lesions on vocal cords

Abdomen Liver:
massive hepatomegaly (patient a)

Skeletal Limbs:
polyarticular arthritis (involving wrists, knees, and ankles)
bilateral medial metaphyseal lesions in femora
abnormal striations of distal femoral metaphyses
dense and irregular condensations in metaphyseal plates of distal femur and proximal tibia

Skin Nails Hair Nails:
dyskeratotic nails

Metabolic Features:
recurrent episodes of fever

Clinical features from OMIM:

617388

GenomeRNAi Phenotypes related to Autoinflammation with Arthritis and Dyskeratosis according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.4 CASP1 IL18 NLRP1
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.4 CASP1 IL18 NLRP1

Drugs & Therapeutics for Autoinflammation with Arthritis and Dyskeratosis

Drugs for Autoinflammation with Arthritis and Dyskeratosis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 14)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Colchicine Approved Phase 4 64-86-8 6167 2833
2 Tubulin Modulators Phase 4
3 Antimitotic Agents Phase 4
4 Antirheumatic Agents Phase 4
5 Antibodies Phase 3
6 Immunoglobulins Phase 3
7 Antibodies, Monoclonal Phase 3
8 Immunologic Factors Phase 3
9 Interleukin 1 Receptor Antagonist Protein Phase 3
10 Pharmaceutical Solutions Phase 3
11
Rilonacept Approved, Investigational Phase 2 501081-76-1 104924
12 Givinostat hydrochloride Phase 2
13 Histone Deacetylase Inhibitors Phase 2
14 Anti-Inflammatory Agents Phase 2

Interventional clinical trials:

(show all 25)
# Name Status NCT ID Phase Drugs
1 The Comparison of the Efficacy of Once and Twice Daily Colchicine Dosage in Pediatric Patients With Familial Mediterranean Fever: A Randomized Trial Completed NCT02602028 Phase 4 colchicine
2 A French Open-label Extension Study of Canakinumab in Patients Who Participated in International Phase III Studies CACZ885G2301E1 or CACZ885G2306 in Systemic Juvenile Idiopathic Arthritis and CACZ885N2301 in Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF) Completed NCT02334748 Phase 3 canakinumab
3 A Randomized Placebo-Controlled Study of the Efficacy and Safety of Kineret (Anakinra), in Adult Patients With Colchicine-Resistant Familial Mediterranean Fever Completed NCT01705756 Phase 3 Kineret
4 A Randomized, Double-blind, Placebo Controlled Study of Canakinumab in Patients With Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF), With Subsequent Randomized Withdrawal/Dosing Frequency Reduction and Open-label Long-term Treatment Epochs Completed NCT02059291 Phase 3 Canakinumab;Placebo
5 The Effects and Side Effects of ITS2357 in Autoinflammatory Syndromes Unknown status NCT00442182 Phase 2 ITF2357
6 Controlled Ceasing of Colchicine Therapy in Familial Mediterranean Fever (FMF) Patients With Single MEFV (Mediterranean Fever) Gene Mutation Unknown status NCT02175589 Phase 2
7 An Open-label, Exploratory Study to Establish the Safety and Efficacy of 3 Months Treatment With Canakinumab in Patients With Colchicine Resistant Familial Mediterranean Fever Completed NCT01088880 Phase 2 Canakinumab
8 A 6 Month Phase 2, Multi-Center, Open-label, Single Arm Study to Evaluate the Safety and Efficacy of Treatment With Canakinumab in Pediatric Patients With Colchicine Intolerant or Colchicine Resistant Familial Mediterranean Fever Completed NCT01148797 Phase 2 Canakinumab
9 An Open-label, Multicenter, Efficacy and Safety Study of 4-month Canakinumab Treatment With 6-month Follow-up in Patients With Active Recurrent or Chronic TNF-receptor Associated Periodic Syndrome (TRAPS). Completed NCT01242813 Phase 2 ACZ885
10 Phase 2 Study of IL-1 Trap (Rilonacept) for Treatment of Familial Mediterranean Fever (FMF) Completed NCT00582907 Phase 2 Rilonacept;Placebo
11 A Pilot Open-Label Study of Rilonacept (Arcalyst) in the Deficiency of the Interleukin-1 Receptor Antagonist (DIRA) Completed NCT01801449 Phase 2 Rilonacept
12 Continuation of a Pilot Open-Label Study of IL 1 Trap in Adult Subjects With Autoinflammatory Diseases: A Therapeutic Approach to Study Pathogenesis Completed NCT00094900 Phase 2 IL-1 Trap
13 Tocilizumab for the Treatment of Familial Mediterranean Fever - A Randomized, Doubleblind, Phase II Proof of Concept Study Recruiting NCT03446209 Phase 2 Tocilizumab Infusion RoAcemtra (EU);0.9% physiological saline
14 An Open-label, Parallel-group, Multiple-Dose, Pharmacokinetic and Safety Study of Colchicine Pediatric Formulation in Pediatric and Adult Patients With FMF Completed NCT01075906 Phase 1 colchicine sprinkle capsules;colchicine sprinkle capsules
15 Exertional Muscle Fatigue In FMF Patients Evaluated By MRI And MR Spectroscopy Of The Thigh Unknown status NCT00658060
16 Gluten-related Disorders in Patients Affected With Familial Mediterranean Fever Completed NCT03563300
17 Clinical and Multi-omics Cross-phenotyping of Patients With Autoimmune and Auto-inflammatory Diseases Recruiting NCT02466217
18 Genetics and Pathophysiology of Autoinflammatory Disorders. Recruiting NCT00001373
19 Creation of a Tool to Assess Quality of Life in Patient With Auto-inflammatory Diseases Active, not recruiting NCT03569644
20 Heat Intolerance in the Group of FMF Patients Enrolling by invitation NCT01059279
21 Assessment of a Functional Test to Detect Familial Mediterranean Fever Not yet recruiting NCT03747315
22 Immunome Project Consortium for Autoinflammatory Disorders Not yet recruiting NCT03919110
23 Musculoskeletal Ultrasound of the Ankles in Erysipelas-like Erythema of Familial Mediterranean Fever Not yet recruiting NCT03917277
24 The Effect of Probiotics on Response to Therapy and on Adverse Effect in Patients Treated With Colchicine for Familial Mediterranean Fever. Withdrawn NCT02021084
25 Inflammatory Proteins in Familial Mediterranean Fever During Attack and Remission Withdrawn NCT00323440

Search NIH Clinical Center for Autoinflammation with Arthritis and Dyskeratosis

Cochrane evidence based reviews: hereditary autoinflammatory diseases

Genetic Tests for Autoinflammation with Arthritis and Dyskeratosis

Anatomical Context for Autoinflammation with Arthritis and Dyskeratosis

MalaCards organs/tissues related to Autoinflammation with Arthritis and Dyskeratosis:

41
Skin, B Cells, Thyroid, Testes

Publications for Autoinflammation with Arthritis and Dyskeratosis

Articles related to Autoinflammation with Arthritis and Dyskeratosis:

# Title Authors PMID Year
1
A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis). 38 8 71
27965258 2017
2
Vitamin a deficiency phrynoderma associated with chronic giardiasis. 8 71
16918630 2006
3
Transient left bundle branch block and left ventricular dysfunction in a patient with NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome. 38
30681047 2019
4
Human DPP9 represses NLRP1 inflammasome and protects against autoinflammatory diseases via both peptidase activity and FIIND domain binding. 38
30291141 2018
5
A clinical update on inflammasomopathies. 38
28387826 2017

Variations for Autoinflammation with Arthritis and Dyskeratosis

ClinVar genetic disease variations for Autoinflammation with Arthritis and Dyskeratosis:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 NLRP1 NM_001033053.3(NLRP1): c.3653C> G (p.Pro1218Arg) single nucleotide variant Pathogenic rs1057524876 17:5424986-5424986 17:5521666-5521666
2 NLRP1 NM_001033053.3(NLRP1): c.2176C> T (p.Arg726Trp) single nucleotide variant Uncertain significance rs776245016 17:5461840-5461840 17:5558520-5558520

Expression for Autoinflammation with Arthritis and Dyskeratosis

Search GEO for disease gene expression data for Autoinflammation with Arthritis and Dyskeratosis.

Pathways for Autoinflammation with Arthritis and Dyskeratosis

Pathways related to Autoinflammation with Arthritis and Dyskeratosis according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.43 NLRP1 IL18 CASP1
2
Show member pathways
12.14 IL18 CASP1
3 11.7 NLRP1 CASP1
4
Show member pathways
11.47 IL18 CASP1
5
Show member pathways
11.46 NLRP1 CASP1
6 11.28 IL18 CASP1
7 11 IL18 CASP1
8 10.74 NLRP1 IL18 CASP1
9 10.14 NLRP1 IL18 CASP1
10 10 IL18 CASP1

GO Terms for Autoinflammation with Arthritis and Dyskeratosis

Cellular components related to Autoinflammation with Arthritis and Dyskeratosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 NLRP1 inflammasome complex GO:0072558 8.62 NLRP1 CASP1

Biological processes related to Autoinflammation with Arthritis and Dyskeratosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 inflammatory response GO:0006954 9.37 NLRP1 IL18
2 cytokine-mediated signaling pathway GO:0019221 9.32 IL18 CASP1
3 regulation of apoptotic process GO:0042981 9.26 NLRP1 CASP1
4 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006919 9.16 NLRP1 CASP1
5 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043280 8.96 NLRP1 CASP1
6 positive regulation of interleukin-1 beta secretion GO:0050718 8.62 NLRP1 CASP1

Molecular functions related to Autoinflammation with Arthritis and Dyskeratosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cysteine-type endopeptidase activator activity involved in apoptotic process GO:0008656 8.62 NLRP1 CASP1

Sources for Autoinflammation with Arthritis and Dyskeratosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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