Factor XIII, A Subunit, Deficiency of

Associated Genes

Factor XIII, A1 Subunit
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WHO-ICD-10 version:2010

Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism

Coagulation defects, purpura and other haemorrhagic conditions

OMIM Number

613225

Mode of Inheritance

Autosomal recessive

Gene Map Locus

6p25.1

Description

Congenital factor XIII (FXIII) deficiency is a rare inherited or acquired bleeding disorder, initially known as Duckert in 1960 with an estimated prevalence of 1/2,000,000 and an estimated incidence of 1/5,000,000 births. It is described as frequent hemorrhagic diathesis correlated with spontaneous abortions, defective wound healing, and results from reduced levels and activity of FXIII which is engaged in stabilizing the blood clot formation. It affects both genders and all ethnic groups equally and can reveal itself at any age; however, it appears more frequently throughout infancy. About 80% of FXIII deficiency patients suffer from umbilical stump bleeding, 25-30% experience intracranial hemorrhage, 20% endure hemarthroses, soft tissue bleeding, bruising, and recurrent spontaneous abortions. The majority of cases tolerate 12-36 hrs of belated hemorrhages following trauma or surgery and subjects might experience reduced wound healing. FXIII deficiency is diagnosed through the quantitative FXIII activity measurement, antigen assays, and the clot solubility analysis (in case of FXIII deficiency a stable clot over 24 hrs is revealed). Differential diagnosis generally consists of the other congenital coagulation factor deficiencies including fibrinogen, factors II, V, VII, X, XI, VIII, and IX. Additionally, antenatal diagnosis is employed when a causal mutation is detected earlier in the family. The bleedings are treated with factor XIII concentrates or fresh frozen plasma, while recurrent bleedings like intracranial hemorrhage are treated and prevented through prophylactic therapy with FXIII concentrate.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
613225.1.1LebanonMaleNoYes Prolonged partial thromboplastin time; ...NM_000129.3:c.1475_1476delGAHomozygousAutosomal, RecessiveKhalife et al, 2008
613225.2.1LebanonMaleYesYes Reduced factor XIII activity; Persisten...NM_000129.3:c.1475_1476delGAHomozygousAutosomal, RecessiveFarah et al, 2014 Proband
613225.2.2LebanonMaleYesYes Reduced factor XIII activity; Prolonged...NM_000129.3:c.1475_1476delGAHomozygousAutosomal, RecessiveFarah et al, 2014 Brother of 613225.2....
613225.3.1SyriaMaleNoNo Vesicoureteral reflux; Prolonged bleedi...NM_000129.3:c.782G>AHomozygousAutosomal, RecessiveKangsadalampai et al. 1999
613225.4.1LebanonMaleYesYes Prolonged bleeding following circumcisio...NM_000129.3:c.1475_1476delGAHomozygousAutosomal, RecessiveEl Rassy et al, 2015

Other Reports

Kuwait

The first case of factor XIII deficiency in Kuwait was reported by Al-Sharkawy et al, 2006, at Al-Sabah Hospital. The case presented a Kuwaiti boy aged one year and seven months. He was the first child born to second cousins of Iranian ancestry. He had recurrent bleeding episodes following minor injuries and was treated with cryoprecipitate. The patient remains healthy and keeps developing normally under the use of two units of cryoprecipitate prophylaxis every three weeks.

[Al-Sharkawy IA, Aboobaker KC, Bourhama MH. Factor XIII deficiency in a Kuwaiti child: typical presentation with delayed diagnosis. Kuwait Med J. 2006; 38(2): 147-8.]

Morocco

Fisher et al, 1966, described an affected Moroccan woman who was the offspring of an uncle-niece mating. Parents and sibs were apparently normal, suggesting autosomal recessive inheritance.

Palestine

Frydman et al, 1985, found linkage between factor XIII deficiency and HLA on chromosome 6p in at least six affected persons spanning two generations. Later, Frydman et al, 1986, found seven homozygotes for factor XIII deficiency in a large inbred Arab kindred. Two affected men and one probably affected man had children, two of whom were also affected. Paternity was confirmed by special tests. An affected woman had early abortions.

[Frydman M., Farrer LA, Bonne-Tamir B, Zamir R. The locus for factor XIII deficiency linked to the HLA region on chromosome 6p. Am J Hum Genet. 1985; 37:A53only]

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