MCID: AFB002
MIFTS: 53

Afibrinogenemia, Congenital

Categories: Genetic diseases, Blood diseases, Rare diseases

Aliases & Classifications for Afibrinogenemia, Congenital

MalaCards integrated aliases for Afibrinogenemia, Congenital:

Name: Afibrinogenemia, Congenital 54 29 13
Congenital Afibrinogenemia 12 25 71 52 14
Afibrinogenemia 25 42 69
Familial Afibrinogenemia 25 56
Complement Factor I Deficiency 69
Hypofibrinogenemia, Congenital 54
Congenital Hypofibrinogenemia 69
Familial Hypofibrinogenemia 56
Fibrinogen Deficiency 12
Factor I Deficiency 12
Hypofibrinogenemia 69
Cafbn 71

Characteristics:

Orphanet epidemiological data:

56
familial afibrinogenemia
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;
familial hypofibrinogenemia
Inheritance: Autosomal dominant; Age of onset: All ages;

OMIM:

54
Inheritance:
autosomal recessive


HPO:

32
afibrinogenemia, congenital:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Afibrinogenemia, Congenital

OMIM : 54
Inherited disorders of fibrinogen affect either the quantity (afibrinogenemia and hypofibrinogenemia; 202400) or the quality (dysfibrinogenemia; 616004) of the circulating fibrinogen or both (hypodysfibrinogenemia; see 616004). Afibrinogenemia is characterized by the complete absence of immunoreactive fibrinogen. Bleeding due to afibrinogenemia usually manifests in the neonatal period, with 85% of cases presenting umbilical cord bleeding, but a later age of onst is not unusual. Bleeding may occur in the skin, gastrointestinal tract, genitourinary tract, or the central nervous system, with intracranial hemorrhage being reported as the major cause of death. Patients are susceptible to spontaneous rupture of the spleen. Menstruating women may experience menometrorrhagia. First-trimester abortion is common. Both arterial and venous thromboembolic complications have been reported (summary by de Moerloose and Neerman-Arbez, 2009). Hypofibrinogenemia is characterized by reduced amounts of immunoreactive fibrinogen. Patients are often heterozygous carriers of afibrinogenemia mutations and are usually asymptomatic. However, they may bleed when exposed to trauma or if they have a second associated hemostatic abnormality. Women may experience miscarriages. Liver disease occurs in rare cases (summary by de Moerloose and Neerman-Arbez, 2009). (202400)

MalaCards based summary : Afibrinogenemia, Congenital, also known as congenital afibrinogenemia, is related to complement factor i deficiency and fibrinogen deficiency, congenital, and has symptoms including epistaxis, cerebral hemorrhage and abnormal bleeding. An important gene associated with Afibrinogenemia, Congenital is FGA (Fibrinogen Alpha Chain), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Development Angiotensin activation of ERK. The drug Complement Factor I has been mentioned in the context of this disorder. Affiliated tissues include liver, skin and brain, and related phenotypes are cardiovascular system and hematopoietic system

UniProtKB/Swiss-Prot : 71 Congenital afibrinogenemia: Rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen.

Genetics Home Reference : 25 Congenital afibrinogenemia is a bleeding disorder caused by impairment of the blood clotting process. Normally, blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss. However, bleeding is uncontrolled in people with congenital afibrinogenemia. Newborns with this condition often experience prolonged bleeding from the umbilical cord stump after birth. Nosebleeds (epistaxis) and bleeding from the gums or tongue are common and can occur after minor trauma or in the absence of injury (spontaneous bleeding). Some affected individuals experience bleeding into the spaces between joints (hemarthrosis) or the muscles (hematoma). Rarely, bleeding in the brain or other internal organs occurs, which can be fatal. Women with congenital afibrinogenemia can have abnormally heavy menstrual bleeding (menorrhagia). Without proper treatment, women with this disorder may have difficulty carrying a pregnancy to term, resulting in repeated miscarriages.

Related Diseases for Afibrinogenemia, Congenital

Diseases in the Afibrinogenemia family:

Afibrinogenemia, Congenital Fga-Related Congenital Afibrinogenemia
Fgb-Related Congenital Afibrinogenemia Fgg-Related Congenital Afibrinogenemia

Diseases related to Afibrinogenemia, Congenital via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 130)
id Related Disease Score Top Affiliating Genes
1 complement factor i deficiency 12.4
2 fibrinogen deficiency, congenital 12.0
3 fga-related congenital afibrinogenemia 11.8
4 fgb-related congenital afibrinogenemia 11.8
5 fgg-related congenital afibrinogenemia 11.8
6 growth retardation with deafness and mental retardation due to igf1 deficiency 11.5
7 insulin-like growth factor i 11.4
8 afibrinogenemia 11.3
9 complement factor h deficiency 10.8
10 ciliary discoordination, due to random ciliary orientation 10.7 FGA FGB
11 ubqln2-related amyotrophic lateral sclerosis/frontotemporal dementia 10.6 F8 VWF
12 uchl1-related parkinson disease susceptibility 10.5 F8 VWF
13 mild hemophilia b 10.5 F8 VWF
14 floppy infant syndrome 10.5 F8 VWF
15 ube2t-related fanconi anemia 10.5 F8 VWF
16 amyloidosis, familial visceral 10.5 FGA FGB FGG
17 mitochondrial phosphate carrier deficiency 10.5 C3 F8
18 guillain-barre syndrome 10.5 CR1 F8
19 glomangiomyoma 10.5 F8 VWF
20 renal adenoma 10.4 F8 VWF
21 anterior cerebral artery infarction 10.4 CR1 FGB
22 gum cancer 10.4 C3 F2
23 autonomic peripheral neuropathy 10.4 C3 VWF
24 social phobia 10.4 F2 F8
25 atrophic vulva 10.4 C3 F2
26 brain ependymoma 10.4 F2 VWF
27 autonomic neuropathy 10.4 F2 F8
28 rheumatoid lung disease 10.4 F2 F8
29 intestinal pseudo-obstruction 10.3 F2 F8
30 otospondylomegaepiphyseal dysplasia 10.3 C3 F3
31 neuroaxonal dystrophy 10.3 F2 F8
32 chronic progressive external ophthalmoplegia 10.3 C3 CFI VWF
33 hemolytic uremic syndrome, atypical 3 10.2 C3 CFI CR1
34 rete ovarii adenoma 10.2 F2 F8
35 multiple congenital anomalies mental retardation, growth failure and cleft lip palate 10.2 F3 F8
36 granuloma annulare 10.2 C3 CFI CR1
37 hyperthyroidism 10.2 F2 F3
38 diffuse glomerulonephritis 10.2 C3 CR1
39 pyridoxine deficiency anemia 10.2 F2 F3
40 46,xy ovotesticular disorder of sex development 10.2 F2 F3
41 myiasis 10.2 F2 F3
42 testicular gonadoblastoma 10.2 F2 F3
43 rectum neuroendocrine neoplasm 10.2 F2 F3
44 midline cystocele 10.1 F2 F3
45 brain stem glioma 10.1 F2 F3
46 sporotrichosis 10.1 F2 F3
47 central nervous system germ cell tumor 10.1 F2 F3
48 monocular exotropia 10.1 F3 VWF
49 chronic inflammatory demyelinating polyneuritis 10.1 F2 F3
50 lymphatic system cancer 10.1 F2 F3

Graphical network of the top 20 diseases related to Afibrinogenemia, Congenital:



Diseases related to Afibrinogenemia, Congenital

Symptoms & Phenotypes for Afibrinogenemia, Congenital

Symptoms via clinical synopsis from OMIM:

54

Abdomen:
splenic rupture

Lab:
afibrinogenemia

Heme:
blood completely incoagulable
bleeding mild to severe
osseous hemorrhage
hepatic hemorrhage


Clinical features from OMIM:

202400

Human phenotypes related to Afibrinogenemia, Congenital:

56 32 (show all 10)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 epistaxis 56 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000421
2 cerebral hemorrhage 56 32 occasional (7.5%) Occasional (29-5%) HP:0001342
3 abnormal bleeding 56 32 Very frequent (99-80%),Very frequent (99-80%) HP:0001892
4 joint swelling 56 32 hallmark (90%) Very frequent (99-80%) HP:0001386
5 gingival bleeding 56 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000225
6 gastrointestinal hemorrhage 56 32 hallmark (90%) Very frequent (99-80%) HP:0002239
7 menometrorrhagia 56 32 hallmark (90%) Very frequent (99-80%) HP:0400008
8 spontaneous abortion 56 32 hallmark (90%) Very frequent (99-80%) HP:0005268
9 splenic rupture 32 HP:0012223
10 hypofibrinogenemia 32 HP:0011900

MGI Mouse Phenotypes related to Afibrinogenemia, Congenital:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.86 C3 F11 F2 F3 FGA FGB
2 hematopoietic system MP:0005397 9.81 C3 CFI F11 F2 F3 F8
3 homeostasis/metabolism MP:0005376 9.65 VWF C3 CFI F11 F2 F3
4 immune system MP:0005387 9.23 C3 F11 F2 F3 F8 FGA

Drugs & Therapeutics for Afibrinogenemia, Congenital

Drugs for Afibrinogenemia, Congenital (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Complement Factor I

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Human Fibrinogen Concentrate (FGTW) in Pediatric Patients With Congenital Fibrinogen Deficiency Completed NCT02094430 Phase 2, Phase 3 biological: human fibrinogen concentrate
2 Pharmacokinetic, Efficacy and Safety of BT524 in Patients With Congenital Fibrinogen Deficiency Recruiting NCT02065882 Phase 2, Phase 3
3 Efficacy and Safety Study of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery Recruiting NCT02267226 Phase 3 Octafibrin
4 Study to Assess the Efficacy, Safety and Pharmacokinetic of Octafibrin in Paediatric Subjects With Fibrinogen Deficiency Recruiting NCT02408484 Phase 3
5 Fibrinogen Concentrate (Human) − Efficacy and Safety Study Withdrawn NCT00916656 Phase 3
6 Pharmacokinetic, Efficacy, and Safety Study of Octafibrin Compared to Haemocomplettan/Riastap Completed NCT01575756 Phase 2
7 Human Fibrinogen - Pharmacokinetics Completed NCT00496262 Phase 2
8 Pharmacokinetics, Efficacy, and Safety of Human Plasma-Derived Fibrinogen (FIB Grifols) in Patients With Congenital Afibrinogenaemia Recruiting NCT02281500 Phase 1, Phase 2
9 An Observational Cohort Study of the Safety and Efficacy of Fibrinogen Concentrate, Human (FCH) in Subjects With Congenital Fibrinogen Deficiency Active, not recruiting NCT02427217

Search NIH Clinical Center for Afibrinogenemia, Congenital

Cochrane evidence based reviews: afibrinogenemia

Genetic Tests for Afibrinogenemia, Congenital

Genetic tests related to Afibrinogenemia, Congenital:

id Genetic test Affiliating Genes
1 Afibrinogenemia, Congenital 29

Anatomical Context for Afibrinogenemia, Congenital

MalaCards organs/tissues related to Afibrinogenemia, Congenital:

39
Liver, Skin, Brain, Spleen, Tongue

Publications for Afibrinogenemia, Congenital

Variations for Afibrinogenemia, Congenital

UniProtKB/Swiss-Prot genetic disease variations for Afibrinogenemia, Congenital:

71 (show all 13)
id Symbol AA change Variation ID SNP ID
1 FGA p.Cys55Arg VAR_072721
2 FGA p.Arg129Pro VAR_072722
3 FGA p.Cys184Trp VAR_072723
4 FGB p.Arg196Cys VAR_016908 rs121909623
5 FGB p.Leu383Arg VAR_016909 rs121909621
6 FGB p.Gly430Asp VAR_016910 rs121909622
7 FGB p.Leu202Gln VAR_072620 rs121909624
8 FGB p.Cys95Arg VAR_072724
9 FGB p.Thr407Lys VAR_072725
10 FGG p.Thr303Pro VAR_072726
11 FGG p.Asp327His VAR_072727
12 FGG p.Asn345Asp VAR_072728
13 FGG p.Arg401Trp VAR_072729 rs75848804

ClinVar genetic disease variations for Afibrinogenemia, Congenital:

6 (show all 19)
id Gene Variation Type Significance SNP ID Assembly Location
1 CFI NM_000204.4(CFI): c.1253A> T (p.His418Leu) single nucleotide variant Pathogenic rs121964912 GRCh37 Chromosome 4, 110667554: 110667554
2 CFI CFI, IVS5DS G-A, -1 single nucleotide variant Pathogenic
3 CFI CFI, 2-BP INS, 1205AT insertion Pathogenic
4 CFI NM_000204.4(CFI): c.728G> A (p.Gly243Asp) single nucleotide variant Pathogenic rs121964916 GRCh37 Chromosome 4, 110681723: 110681723
5 FGG NM_021870.2(FGG): c.78+5G> A single nucleotide variant Pathogenic rs587776837 GRCh38 Chromosome 4, 154612527: 154612527
6 FGG NM_021870.2(FGG): c.307+5G> A single nucleotide variant Pathogenic rs587776838 GRCh37 Chromosome 4, 155533165: 155533165
7 FGG NM_021870.2(FGG): c.667-320A> T single nucleotide variant Pathogenic rs587776839 GRCh38 Chromosome 4, 154608970: 154608970
8 FGB NM_005141.4(FGB): c.1148T> G (p.Leu383Arg) single nucleotide variant Pathogenic rs121909621 GRCh37 Chromosome 4, 155490855: 155490855
9 FGB NM_005141.4(FGB): c.1289G> A (p.Gly430Asp) single nucleotide variant Pathogenic rs121909622 GRCh37 Chromosome 4, 155491615: 155491615
10 FGB NM_005141.4(FGB): c.958+13C> T single nucleotide variant Pathogenic rs606231223 GRCh38 Chromosome 4, 154569320: 154569320
11 FGB NM_005141.4(FGB): c.1244+1G> T single nucleotide variant Pathogenic rs606231224 GRCh38 Chromosome 4, 154569800: 154569800
12 FGB NM_005141.4(FGB): c.605T> A (p.Leu202Gln) single nucleotide variant Pathogenic rs121909624 GRCh37 Chromosome 4, 155488859: 155488859
13 FGB NM_005141.4(FGB): c.139C> T (p.Arg47Ter) single nucleotide variant Pathogenic rs121909625 GRCh37 Chromosome 4, 155486984: 155486984
14 FGA NC_000004.12 deletion Pathogenic GRCh38 Chromosome 4, 154580323: 154590216
15 FGA NM_000508.4(FGA): c.510+1G> T single nucleotide variant Pathogenic rs146387238 GRCh37 Chromosome 4, 155508663: 155508663
16 FGA NM_000508.4(FGA): c.711dupT (p.Lys238Terfs) duplication Pathogenic rs606231225 GRCh38 Chromosome 4, 154586718: 154586718
17 FGA NM_000508.4(FGA): c.991A> G (p.Thr331Ala) single nucleotide variant risk factor rs6050 GRCh37 Chromosome 4, 155507590: 155507590
18 CFI NM_000204.4(CFI): c.80_81delAT (p.Asp27Alafs) deletion Pathogenic rs886043418 GRCh37 Chromosome 4, 110687957: 110687958
19 FGA NM_000508.4(FGA): c.502C> T (p.Arg168Ter) single nucleotide variant Pathogenic rs755117226 GRCh37 Chromosome 4, 155508672: 155508672

Expression for Afibrinogenemia, Congenital

Search GEO for disease gene expression data for Afibrinogenemia, Congenital.

Pathways for Afibrinogenemia, Congenital

Pathways related to Afibrinogenemia, Congenital according to GeneCards Suite gene sharing:

(show all 15)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
13.05 F11 F2 F3 F8 FGA FGB
2
Show member pathways
12.61 F2 FGA FGB FGG
3
Show member pathways
12.59 F11 F2 F3 F8 FGA FGB
4
Show member pathways
12.1 FGA FGB FGG VWF
5
Show member pathways
11.93 FGA FGB FGG VWF
6
Show member pathways
11.87 C3 CFI CR1
7
Show member pathways
11.87 FGA FGB FGG VWF
8
Show member pathways
11.83 C3 CFI CR1
9 11.79 FGA FGB FGG VWF
10
Show member pathways
11.76 F11 F2 F3 F8 FGA FGB
11
Show member pathways
11.65 F2 FGA FGB FGG VWF
12 11.51 C3 CFI CR1 F11 F2 F3
13 11.43 C3 CFI FGG
14 11.34 FGA FGB FGG
15 11.26 F2 FGA FGB FGG VWF

GO Terms for Afibrinogenemia, Congenital

Cellular components related to Afibrinogenemia, Congenital according to GeneCards Suite gene sharing:

(show all 11)
id Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.91 C3 CFI F11 F2 F3 F8
2 cell surface GO:0009986 9.85 CR1 F3 FGA FGB FGG
3 extracellular region GO:0005576 9.85 C3 CFI F11 F2 F3 F8
4 endoplasmic reticulum lumen GO:0005788 9.83 C3 F2 F8 FGA FGG
5 external side of plasma membrane GO:0009897 9.78 F2 FGA FGB FGG
6 blood microparticle GO:0072562 9.77 C3 F2 FGA FGB FGG
7 fibrinogen complex GO:0005577 9.5 FGA FGB FGG
8 platelet alpha granule lumen GO:0031093 9.35 F8 FGA FGB FGG VWF
9 platelet alpha granule GO:0031091 8.92 FGA FGB FGG VWF
10 plasma membrane GO:0005886 10.15 C3 CR1 F11 F2 F3 F8
11 extracellular exosome GO:0070062 10.1 C3 CFI CR1 F11 F2 F3

Biological processes related to Afibrinogenemia, Congenital according to GeneCards Suite gene sharing:

(show all 32)
id Name GO ID Score Top Affiliating Genes
1 immune system process GO:0002376 9.95 C3 CR1 FGA FGB
2 cellular protein metabolic process GO:0044267 9.92 C3 F2 FGA FGG
3 extracellular matrix organization GO:0030198 9.91 FGA FGB FGG VWF
4 regulation of complement activation GO:0030449 9.84 C3 CFI CR1 F2
5 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.83 FGA FGB FGG
6 platelet degranulation GO:0002576 9.83 F8 FGA FGB FGG VWF
7 complement activation, classical pathway GO:0006958 9.81 C3 CFI CR1
8 cell-matrix adhesion GO:0007160 9.81 FGA FGB FGG
9 response to calcium ion GO:0051592 9.8 FGA FGB FGG
10 toll-like receptor signaling pathway GO:0002224 9.77 FGA FGB FGG
11 platelet aggregation GO:0070527 9.77 FGA FGB FGG
12 positive regulation of protein secretion GO:0050714 9.76 FGA FGB FGG
13 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902042 9.75 FGA FGB FGG
14 positive regulation of substrate adhesion-dependent cell spreading GO:1900026 9.74 FGA FGB FGG
15 positive regulation of vasoconstriction GO:0045907 9.73 FGA FGB FGG
16 negative regulation of endothelial cell apoptotic process GO:2000352 9.72 FGA FGB FGG
17 positive regulation of exocytosis GO:0045921 9.7 FGA FGB FGG
18 cellular protein complex assembly GO:0043623 9.69 FGA FGB FGG
19 protein polymerization GO:0051258 9.67 FGA FGB FGG
20 fibrinolysis GO:0042730 9.67 F2 FGA FGB FGG
21 acute-phase response GO:0006953 9.65 F2 F8
22 positive regulation of heterotypic cell-cell adhesion GO:0034116 9.65 FGA FGB FGG
23 regulation of blood coagulation GO:0030193 9.64 F11 F2
24 induction of bacterial agglutination GO:0043152 9.63 FGA FGB
25 positive regulation of peptide hormone secretion GO:0090277 9.63 FGA FGB FGG
26 platelet activation GO:0030168 9.63 F2 F8 FGA FGB FGG VWF
27 blood coagulation, intrinsic pathway GO:0007597 9.62 F11 F2 F8 VWF
28 blood coagulation, fibrin clot formation GO:0072378 9.58 FGA FGB FGG
29 plasminogen activation GO:0031639 9.56 F11 FGA FGB FGG
30 blood coagulation GO:0007596 9.56 F11 F2 F3 F8 FGA FGB
31 hemostasis GO:0007599 9.23 F11 F2 F3 F8 FGA FGB
32 innate immune response GO:0045087 10.01 C3 CFI CR1 FGA FGB

Molecular functions related to Afibrinogenemia, Congenital according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 serine-type peptidase activity GO:0008236 9.5 CFI F11 F2
2 protein binding, bridging GO:0030674 9.43 FGA FGB FGG
3 receptor binding GO:0005102 9.35 C3 F2 FGA FGB FGG
4 cell adhesion molecule binding GO:0050839 9.33 FGA FGB FGG
5 serine-type endopeptidase activity GO:0004252 9.02 C3 CFI F11 F2 F3

Sources for Afibrinogenemia, Congenital

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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