MCID: THR054
MIFTS: 43

Thrombotic Thrombocytopenic Purpura, Familial

Categories: Genetic diseases, Rare diseases, Nephrological diseases, Blood diseases

Aliases & Classifications for Thrombotic Thrombocytopenic Purpura, Familial

MalaCards integrated aliases for Thrombotic Thrombocytopenic Purpura, Familial:

Name: Thrombotic Thrombocytopenic Purpura, Familial 54 50 13
Microangiopathic Hemolytic Anemia 50 71 29 69
Upshaw-Schulman Syndrome 50 56 71 29
Congenital Thrombotic Thrombocytopenic Purpura 56 69
Schulman-Upshaw Syndrome 50 71
Ttp 56 71
Uss 50 71
Thrombotic Thrombocytopenic Purpura, Congenital 50
Thrombotic Thrombocytopenic Purpura Congenital 71
Microangiopathic Hemolytic Anemia, Congenital 50
Microangiopathic Hemolytic Anemia Congenital 71
Thrombotic Thrombocytopenic Purpura Familial 71
Purpura, Thrombotic Thrombocytopenic 69
Thrombotic Microangiopathy, Familial 50
Thrombotic Thrombocytopenic Purpura 56
Thrombotic Microangiopathy Familial 71
Anemia Hemolytic Microangiopathic 52
Congenital Adamts-13 Deficiency 56
Upshaw Factor, Deficiency of 50
Deficiency of Upshaw Factor 71
Moschkowitz Disease 71
Moschcowitz Disease 56
Ttp, Congenital 50
Congenital Ttp 56
Familial Ttp 56

Characteristics:

Orphanet epidemiological data:

56
thrombotic thrombocytopenic purpura
Inheritance: Autosomal recessive,Multigenic/multifactorial; Prevalence: 1-9/1000000 (United States),1-5/10000 (Europe),1-9/1000000 (United Kingdom),1-9/1000000 (Europe); Age of onset: All ages; Age of death: any age;
congenital thrombotic thrombocytopenic purpura
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult,Childhood,Infancy,Neonatal; Age of death: any age;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
genetic heterogeneity
triggered by pregnancy, drugs, chemotherapy, cancer, bone marrow transplantation, infection
familial form - constitutional deficiency of vwf-cleaving protease
acquired form - presence of inhibiting autoantibody (igg) to vwf-cleaving protease
in adults, may be considered part of a spectrum with hemolytic-uremic syndrome (hus, )


HPO:

32
thrombotic thrombocytopenic purpura, familial:
Inheritance heterogeneous autosomal recessive inheritance


Classifications:



Summaries for Thrombotic Thrombocytopenic Purpura, Familial

NIH Rare Diseases : 50 thrombotic thrombocytopenic purpura (ttp), congenital is a blood disorder characterized by low platelets (i.e., thrombocytopenia), small areas of bleeding under the skin (i.e., purpura), low red blood cell count, and hemolytic anemia. ttp causes blood clots (thrombi) to form in small blood vessels throughout the body. these clots can cause serious medical problems if they block vessels and restrict blood flow to organs such as the brain, kidneys, and heart. resulting complications can include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal kidney function, abdominal pain, and heart problems. hemolytic anemia can lead to paleness, yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate. ttp, congenital is much rarer than the acquired form and typically appears in infancy or early childhood. signs and symptoms often recur on a regular basis. ttp, congenital results from mutations in the adamts13 gene. the condition is inherited in an autosomal recessive manner. last updated: 4/7/2011

MalaCards based summary : Thrombotic Thrombocytopenic Purpura, Familial, also known as microangiopathic hemolytic anemia, is related to thrombotic thrombocytopenic purpura, acquired and thrombotic thrombocytopenic purpura, and has symptoms including tremor, reticulocytosis and hemolytic-uremic syndrome. An important gene associated with Thrombotic Thrombocytopenic Purpura, Familial is ADAMTS13 (ADAM Metallopeptidase With Thrombospondin Type 1 Motif 13). The drugs rituximab and Antirheumatic Agents have been mentioned in the context of this disorder. Affiliated tissues include heart, kidney and skin, and related phenotype is pigmentation.

UniProtKB/Swiss-Prot : 71 Thrombotic thrombocytopenic purpura congenital: A hematologic disease characterized by hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decreased renal function and fever. recessive.

OMIM : 54
The classic pentad of TTP includes hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and nonfocal neurologic findings, decreased renal function, and fever. Congenital TTP, also known as Schulman-Upshaw syndrome, is characterized by neonatal onset, response to fresh plasma infusion, and frequent relapses (Savasan et al., 2003; Kokame et al., 2002). Acquired TTP, which is usually sporadic, usually occurs in adults and is caused by an IgG inhibitor against the von Willebrand factor-cleaving protease. (274150)

Related Diseases for Thrombotic Thrombocytopenic Purpura, Familial

Graphical network of the top 20 diseases related to Thrombotic Thrombocytopenic Purpura, Familial:



Diseases related to Thrombotic Thrombocytopenic Purpura, Familial

Symptoms & Phenotypes for Thrombotic Thrombocytopenic Purpura, Familial

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
tremor
confusion
fluctuating neurologic signs
focal neurologic signs
disturbances of consciousness

Laboratory- Abnormalities:
proteinuria
decreased hemoglobin
increased blood urea nitrogen (bun)
increased creatinine
microscopic hematuria
more
Skin Nails & Hair- Skin:
jaundice, neonatal

Genitourinary- Kidneys:
renal dysfunction

Hematology:
reticulocytosis
thrombocytopenia
schistocytes
microangiopathic hemolytic anemia (coomb negative)
thrombotic microangiopathy (hyaline thrombi of platelets and fibrin in terminal arterioles and capillaries)

Metabolic Features:
fever

Abdomen- Liver:
jaundice, neonatal

Respiratory- Lung:
acute respiratory distress syndrome (uncommon)


Clinical features from OMIM:

274150

Human phenotypes related to Thrombotic Thrombocytopenic Purpura, Familial:

32 (show all 15)
id Description HPO Frequency HPO Source Accession
1 tremor 32 HP:0001337
2 reticulocytosis 32 HP:0001923
3 hemolytic-uremic syndrome 32 HP:0005575
4 thrombocytopenia 32 HP:0001873
5 proteinuria 32 HP:0000093
6 increased serum lactate 32 HP:0002151
7 respiratory distress 32 occasional (7.5%) HP:0002098
8 confusion 32 HP:0001289
9 fever 32 HP:0001945
10 microangiopathic hemolytic anemia 32 HP:0001937
11 microscopic hematuria 32 HP:0002907
12 schistocytosis 32 HP:0001981
13 elevated serum creatinine 32 HP:0003259
14 prolonged neonatal jaundice 32 HP:0006579
15 increased blood urea nitrogen 32 HP:0003138

UMLS symptoms related to Thrombotic Thrombocytopenic Purpura, Familial:


fever, tremor, reduced consciousness/confusion

MGI Mouse Phenotypes related to Thrombotic Thrombocytopenic Purpura, Familial:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 pigmentation MP:0001186 8.62 ADAMTS13 CFH

Drugs & Therapeutics for Thrombotic Thrombocytopenic Purpura, Familial

Drugs for Thrombotic Thrombocytopenic Purpura, Familial (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1
rituximab Approved Phase 2 174722-31-7 10201696
2 Antirheumatic Agents Phase 2
3
Bilirubin 635-65-4 5280352
4 N-Methylaspartate
5 Aspartic Acid Nutraceutical

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Prophylactic Plasma Infusion Therapy for Congenital Thrombotic Thrombocytopenic Purpura Withdrawn NCT01754545 Phase 4 Octaplas infusion and placebo (group 1);Octaplas infusion and placebo (group 2)
2 Rituximab in Adult Acquired Idiopathic Thrombotic Thrombocytopenic Purpura Completed NCT00907751 Phase 2 rituximab
3 Clinical Outcome Study of ARC1779 Injection in Patients With Thrombotic Microangiopathy Terminated NCT00726544 Phase 2 ARC 1779 Placebo;ARC1779 Injection;ARC1779 Injection;ARC1779 Injection
4 ADAMTS13 in Thrombotic Thrombocytopenic Purpura Completed NCT00426686
5 Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome) Recruiting NCT01257269
6 Women Specific Cardiac Recovery After Preeclampsia Recruiting NCT02807324
7 The Role of Microparticles as a Biomarker Enrolling by invitation NCT02626663
8 International Registry and Biorepository for TMA(Thrombotic Microangiopathy) Terminated NCT00593229

Search NIH Clinical Center for Thrombotic Thrombocytopenic Purpura, Familial

Genetic Tests for Thrombotic Thrombocytopenic Purpura, Familial

Genetic tests related to Thrombotic Thrombocytopenic Purpura, Familial:

id Genetic test Affiliating Genes
1 Upshaw-Schulman Syndrome 29
2 Microangiopathic Hemolytic Anemia 29

Anatomical Context for Thrombotic Thrombocytopenic Purpura, Familial

MalaCards organs/tissues related to Thrombotic Thrombocytopenic Purpura, Familial:

39
Heart, Kidney, Skin, Brain, Eye, Bone, Bone Marrow

Publications for Thrombotic Thrombocytopenic Purpura, Familial

Articles related to Thrombotic Thrombocytopenic Purpura, Familial:

id Title Authors Year
1
Single-nucleotide variations defining previously unreported ADAMTS13 haplotypes are associated with differential expression and activity of the VWF-cleaving protease in a Salvadoran congenital thrombotic thrombocytopenic purpura family. ( 24433405 )
2014

Variations for Thrombotic Thrombocytopenic Purpura, Familial

UniProtKB/Swiss-Prot genetic disease variations for Thrombotic Thrombocytopenic Purpura, Familial:

71 (show all 43)
id Symbol AA change Variation ID SNP ID
1 ADAMTS13 p.Val88Met VAR_027110 rs281875302
2 ADAMTS13 p.His96Asp VAR_027111 rs121908467
3 ADAMTS13 p.Arg102Cys VAR_027112 rs121908469
4 ADAMTS13 p.Arg193Trp VAR_027113 rs281875287
5 ADAMTS13 p.Thr196Ile VAR_027114 rs121908470
6 ADAMTS13 p.His234Gln VAR_027115 rs281875304
7 ADAMTS13 p.Ala250Val VAR_027116 rs121908478
8 ADAMTS13 p.Arg268Pro VAR_027117 rs121908477
9 ADAMTS13 p.Trp390Cys VAR_027118 rs281875306
10 ADAMTS13 p.Arg398His VAR_027119 rs121908471
11 ADAMTS13 p.Cys508Tyr VAR_027122 rs281875305
12 ADAMTS13 p.Arg528Gly VAR_027123 rs121908473
13 ADAMTS13 p.Ile673Phe VAR_027126 rs281875307
14 ADAMTS13 p.Arg692Cys VAR_027127 rs121908475
15 ADAMTS13 p.Cys908Tyr VAR_027131 rs281875301
16 ADAMTS13 p.Cys951Gly VAR_027132 rs121908468
17 ADAMTS13 p.Cys1024Gly VAR_027133 rs121908472
18 ADAMTS13 p.Arg1123Cys VAR_027136 rs281875340
19 ADAMTS13 p.Cys1213Tyr VAR_027137 rs121908474
20 ADAMTS13 p.Gly1239Val VAR_027138 rs281875303
21 ADAMTS13 p.Arg1336Trp VAR_027139 rs281875308
22 ADAMTS13 p.Ile79Met VAR_067770 rs281875297
23 ADAMTS13 p.Ser119Phe VAR_067771 rs281875291
24 ADAMTS13 p.Ile178Thr VAR_067772 rs281875289
25 ADAMTS13 p.Ser203Pro VAR_067773 rs281875298
26 ADAMTS13 p.Leu232Gln VAR_067774 rs281875292
27 ADAMTS13 p.Asp235His VAR_067775 rs281875337
28 ADAMTS13 p.Ser263Cys VAR_067776 rs281875293
29 ADAMTS13 p.Tyr304Cys VAR_067777 rs281875285
30 ADAMTS13 p.Cys311Tyr VAR_067778 rs281875336
31 ADAMTS13 p.Cys347Ser VAR_067780 rs281875294
32 ADAMTS13 p.Arg349Cys VAR_067781 rs281875288
33 ADAMTS13 p.Pro353Leu VAR_067782 rs281875338
34 ADAMTS13 p.Arg507Gln VAR_067783 rs281875296
35 ADAMTS13 p.Gly525Asp VAR_067784 rs281875286
36 ADAMTS13 p.Ala596Val VAR_067785 rs281875299
37 ADAMTS13 p.Ala606Pro VAR_067786 rs281875290
38 ADAMTS13 p.Tyr658Cys VAR_067787 rs281875335
39 ADAMTS13 p.Pro671Leu VAR_067788 rs281875295
40 ADAMTS13 p.Cys758Arg VAR_067789 rs281875300
41 ADAMTS13 p.Cys908Ser VAR_067790 rs281875301
42 ADAMTS13 p.Arg1060Trp VAR_067792 rs142572218
43 ADAMTS13 p.Arg1219Trp VAR_067793 rs281875339

ClinVar genetic disease variations for Thrombotic Thrombocytopenic Purpura, Familial:

6 (show all 22)
id Gene Variation Type Significance SNP ID Assembly Location
1 ADAMTS13 NM_139025.4(ADAMTS13): c.286C> G (p.His96Asp) single nucleotide variant Pathogenic rs121908467 GRCh37 Chromosome 9, 136289554: 136289554
2 ADAMTS13 NM_139025.4(ADAMTS13): c.2851T> G (p.Cys951Gly) single nucleotide variant Pathogenic rs121908468 GRCh37 Chromosome 9, 136313839: 136313839
3 ADAMTS13 NM_139025.4(ADAMTS13): c.304C> T (p.Arg102Cys) single nucleotide variant Pathogenic rs121908469 GRCh37 Chromosome 9, 136289572: 136289572
4 ADAMTS13 NM_139025.4(ADAMTS13): c.587C> T (p.Thr196Ile) single nucleotide variant Pathogenic rs121908470 GRCh37 Chromosome 9, 136291366: 136291366
5 ADAMTS13 NM_139025.4(ADAMTS13): c.1193G> A (p.Arg398His) single nucleotide variant Pathogenic rs121908471 GRCh37 Chromosome 9, 136298598: 136298598
6 ADAMTS13 NM_139025.4(ADAMTS13): c.3070T> G (p.Cys1024Gly) single nucleotide variant Pathogenic rs121908472 GRCh37 Chromosome 9, 136319562: 136319562
7 ADAMTS13 NM_139025.4(ADAMTS13): c.1582A> G (p.Arg528Gly) single nucleotide variant Pathogenic rs121908473 GRCh37 Chromosome 9, 136303015: 136303015
8 ADAMTS13 NM_139025.4(ADAMTS13): c.3770dupT (p.Leu1258Valfs) duplication Pathogenic rs387906341 GRCh37 Chromosome 9, 136321719: 136321719
9 ADAMTS13 NM_139025.4(ADAMTS13): c.2376_2401del26 (p.Ala793Profs) deletion Pathogenic rs387906342 GRCh37 Chromosome 9, 136308638: 136308663
10 ADAMTS13 NM_139025.4(ADAMTS13): c.4143_4144insA (p.Glu1382Argfs) insertion Pathogenic rs387906343 GRCh37 Chromosome 9, 136324161: 136324161
11 ADAMTS13 NM_139025.4(ADAMTS13): c.3638G> A (p.Cys1213Tyr) single nucleotide variant Pathogenic rs121908474 GRCh37 Chromosome 9, 136321260: 136321260
12 ADAMTS13 NM_139025.4(ADAMTS13): c.2074C> T (p.Arg692Cys) single nucleotide variant Pathogenic rs121908475 GRCh37 Chromosome 9, 136307625: 136307625
13 ADAMTS13 ADAMTS13, IVS13DS, G-A, +5 single nucleotide variant Pathogenic
14 ADAMTS13 NM_139025.4(ADAMTS13): c.1345C> T (p.Gln449Ter) single nucleotide variant Pathogenic rs121908476 GRCh37 Chromosome 9, 136301985: 136301985
15 ADAMTS13 NM_139025.4(ADAMTS13): c.803G> C (p.Arg268Pro) single nucleotide variant Pathogenic rs121908477 GRCh37 Chromosome 9, 136293870: 136293870
16 ADAMTS13 NM_139025.4(ADAMTS13): c.1783_1784delTT (p.Leu595Glyfs) deletion Pathogenic rs387906344 GRCh37 Chromosome 9, 136304564: 136304565
17 ADAMTS13 NM_139025.4(ADAMTS13): c.414+1G> A single nucleotide variant Pathogenic rs786205077 GRCh37 Chromosome 9, 136290733: 136290733
18 ADAMTS13 NM_139025.4(ADAMTS13): c.749C> T (p.Ala250Val) single nucleotide variant Pathogenic rs121908478 GRCh37 Chromosome 9, 136293816: 136293816
19 ADAMTS13 NM_139025.4(ADAMTS13): c.331-1G> A single nucleotide variant Pathogenic rs786205078 GRCh37 Chromosome 9, 136290648: 136290648
20 ADAMTS13 NM_139025.4(ADAMTS13): c.291_319del29 (p.Glu98Profs) deletion Pathogenic rs387906345 GRCh37 Chromosome 9, 136289559: 136289587
21 ADAMTS13 NM_139025.4(ADAMTS13): c.2930_2935delGTGCCC (p.Cys977_Arg979delinsTrp) deletion Pathogenic rs387906346 GRCh37 Chromosome 9, 136314972: 136314977
22 ADAMTS13 NM_139025.4(ADAMTS13): c.3541delG (p.Gln1183Argfs) deletion Likely pathogenic rs1060499780 GRCh38 Chromosome 9, 133455576: 133455576

Expression for Thrombotic Thrombocytopenic Purpura, Familial

Search GEO for disease gene expression data for Thrombotic Thrombocytopenic Purpura, Familial.

Pathways for Thrombotic Thrombocytopenic Purpura, Familial

GO Terms for Thrombotic Thrombocytopenic Purpura, Familial

Cellular components related to Thrombotic Thrombocytopenic Purpura, Familial according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.33 ADAMTS13 CFH HP
2 extracellular space GO:0005615 9.13 ADAMTS13 CFH HP
3 blood microparticle GO:0072562 8.62 CFH HP

Sources for Thrombotic Thrombocytopenic Purpura, Familial

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