Delayed umbilical bleeding--a presenting feature for factor XIII deficiency: clinical features, genetics, and management.

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  • Additional Information
    • Source:
      Publisher: American Academy of Pediatrics Country of Publication: United States NLM ID: 0376422 Publication Model: Print Cited Medium: Internet ISSN: 1098-4275 (Electronic) Linking ISSN: 00314005 NLM ISO Abbreviation: Pediatrics Subsets: MEDLINE
    • Publication Information:
      Publication: Elk Grove Village Il : American Academy of Pediatrics
      Original Publication: Springfield, Ill., Thomas.
    • Subject Terms:
      Factor XIII Deficiency/*diagnosis ; Hemorrhage/*diagnosis ; Umbilical Cord/*physiopathology; Factor XIII/genetics ; Factor XIII/therapeutic use ; Factor XIII Deficiency/drug therapy ; Factor XIII Deficiency/genetics ; Hemorrhage/physiopathology ; Humans ; Models, Molecular ; Mutation ; Nucleic Acid Amplification Techniques ; Sequence Analysis
    • Abstract:
      Objectives: The objectives of this study were 1) to assess the importance of an early diagnosis for factor XIII (FXIII) deficiency, and 2) to investigate the molecular basis and mechanism(s) of disease in the patients under study.
      Methods: The case histories of 6 FXIII-deficient patients were examined to assess the influence of early versus delayed diagnosis and replacement therapy. The nucleotide sequence of the FXIIIA gene was determined to identify the underlying mutations responsible for the bleeding diathesis in each patient. Molecular modeling was used to predict the mechanism(s) of disease causation for each mutation.
      Results: All cases presented with umbilical hemorrhage. Patients 1 to 3 were diagnosed, and their prophylactic therapy was commenced in infancy. Diagnosis in patients 4 to 6 was considerably delayed and, as a result, they continued to suffer from many bleeding symptoms. The FXIIIA gene mutations identified in these patients were as follows: a homozygous GAA-->AAA mutation in codon 102 (Glu102Lys) in patient 1 and a homozygous AGC-->AGG mutation in codon 295 (Ser295Arg) in patients 2 to 6. These mutations segregate with disease and are absent from the normal population, suggesting that they are likely to be disease-causing sequence changes. Computer modeling indicates that both the Lys102 and Arg295 mutants are unable to fold correctly, and probably result in unstable FXIIIA molecules.
      Conclusions: We demonstrate the importance of recognizing delayed umbilical hemorrhage as a presenting feature for congenital FXIII deficiency, and the value of early diagnosis and prophylaxis. The bleeding disorder of patient 1 was attributable to a homozygous Glu102Lys mutation in FXIIIA. A homozygous Ser295Arg mutation in FXIIIA was responsible for FXIII deficiency in patients 2 to 6.
    • Accession Number:
      9013-56-3 (Factor XIII)
    • Publication Date:
      Date Created: 20020205 Date Completed: 20020312 Latest Revision: 20190605
    • Publication Date:
      20221213
    • Accession Number:
      10.1542/peds.109.2.e32
    • Accession Number:
      11826242