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Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder(GURDP)

MedGen UID:
1799074
Concept ID:
C5567651
Disease or Syndrome
Synonyms: Deficiency of phospholipase A2, group IVA; GASTROINTESTINAL ULCERATION, RECURRENT, WITH DYSFUNCTIONAL PLATELETS; GURDP
SNOMED CT: PLA2G4A (phospholipase A2 group IVA) related platelet dysfunction (1172901009); PLA2G4A-related platelet dysfunction (1172901009); Platelet dysfunction due to cytosolic phospholipase-A2 alpha deficiency (1172901009); Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder (1172901009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): PLA2G4A (1q31.1)
 
Monarch Initiative: MONDO:0018794
OMIM®: 618372
Orphanet: ORPHA477787

Definition

Recurrent gastrointestinal ulceration with dysfunctional platelets (GURDP) is an autosomal recessive disorder characterized by onset of severe gastrointestinal mucosal ulceration in early childhood. Affected individuals may have secondary iron deficiency anemia or malnourishment. Studies of platelet aggregation show a functional defect associated with decreased thromboxane-A2 production and decreased eicosanoid biosynthesis. The gastrointestinal disease is believed to result from decreased or absent production of prostaglandins that protect the gut mucosa (summary by Adler et al., 2008 and Faioni et al., 2014). [from OMIM]

Clinical features

From HPO
Duodenal ulcer
MedGen UID:
41670
Concept ID:
C0013295
Disease or Syndrome
An erosion of the mucous membrane in a portion of the duodenum.
Gastric ulcer
MedGen UID:
21330
Concept ID:
C0038358
Disease or Syndrome
An ulcer, that is, an erosion of an area of the gastric mucous membrane.
Esophageal ulceration
MedGen UID:
56254
Concept ID:
C0151970
Disease or Syndrome
Defect in the epithelium of the esophagus, essentially an open sore in the lining of the esophagus.
Iron deficiency anemia
MedGen UID:
57668
Concept ID:
C0162316
Disease or Syndrome
Anemia caused by low iron intake, inefficient iron absorption in the gastrointestinal tract, or chronic blood loss.
Impaired platelet aggregation
MedGen UID:
383786
Concept ID:
C1855853
Finding
An impairment in the rate and degree to which platelets aggregate after the addition of an agonist that stimulates platelet clumping. Platelet aggregation is measured using aggregometer to measure the optical density of platelet-rich plasma, whereby platelet aggregation causes the plasma to become more transparent.
Decreased serum thromboxane B2
MedGen UID:
481610
Concept ID:
C3279980
Finding
A reduction in the concentration of thromboxane B2 in the blood circulation.
Abnormal circulating eicosanoid concentration
MedGen UID:
892588
Concept ID:
C4072901
Finding
Any deviation from the normal concentration in the blood circulation of an icosanoid (also known as eicosanoids). These are signaling molecules derived from oxidation of 20-carbon fatty acids. Most are produced from arachidonic acid, a 20-carbon polyunsaturated fatty acid (5,8,11,14-eicosatetraenoic acid).
Decreased circulating 12-HETE
MedGen UID:
1717477
Concept ID:
C5397602
Finding
A reduction in the concentration of 12-HETE in the blood circulation, a metabolite of arachidonic acid.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCytosolic phospholipase-A2 alpha deficiency associated bleeding disorder

Recent clinical studies

Etiology

Faioni EM, Razzari C, Zulueta A, Femia EA, Fenu L, Trinchera M, Podda GM, Pugliano M, Marongiu F, Cattaneo M
Thromb Haemost 2014 Dec;112(6):1182-9. Epub 2014 Aug 7 doi: 10.1160/TH14-04-0352. PMID: 25102815

Diagnosis

Faioni EM, Razzari C, Zulueta A, Femia EA, Fenu L, Trinchera M, Podda GM, Pugliano M, Marongiu F, Cattaneo M
Thromb Haemost 2014 Dec;112(6):1182-9. Epub 2014 Aug 7 doi: 10.1160/TH14-04-0352. PMID: 25102815

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