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 @entity1 under study. METHODS: The case histories of 6 FXIII-deficient @entity1 were examined to assess the influence of early versus delayed diagnosis and replacement therapy. The @entity377 sequence of the FXIIIA gene was determined to identify the underlying mutations responsible for the @entity548 diathesis in each @entity1 . Molecular modeling was used to predict the mechanism(s) of disease causation for each mutation. RESULTS: All cases presented with umbilical @entity548 . @entity1 1 to 3 were diagnosed, and their prophylactic therapy was commenced in infancy. Diagnosis in @entity1 4 to 6 was considerably delayed and, as a result, they continued to suffer from many @entity548 symptoms. The FXIIIA gene mutations identified in these @entity1 were as follows: a homozygous @entity69684 ( @entity69685 ) in @entity1 1 and a homozygous @entity69686 mutation in codon 295 ( @entity69687 ) in @entity1 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 @entity534 295 mutants are unable to fold correctly, and probably result in unstable FXIIIA molecules. CONCLUSIONS: We demonstrate the importance of recognizing delayed umbilical @entity548 as a presenting feature for @entity19434 , and the value of early diagnosis and prophylaxis. The @entity548 disorder of @entity1 1 was attributable to a homozygous @entity69685 mutation in FXIIIA. A homozygous @entity69687 mutation in FXIIIA was responsible for @entity19434 in @entity1 2 to 6.

Delayed umbilical @entity548 --a presenting feature for XXXX : clinical features, genetics, and management.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'patient'] @entity548 :: ('MESH:D006470', 'Disease') :: ['hemorrhage', 'bleeding'] @entity69687 :: ('p|SUB|S|295|R', 'ProteinMutation') :: ['Ser295Arg'] @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide'] @entity69685 :: ('p|SUB|E|102|K', 'ProteinMutation') :: ['Glu102Lys'] @entity69684 :: ('c|SUB|GAA|102|AAA', 'DNAMutation') :: ['GAA-->AAA mutation in codon 102'] @entity534 :: ('CHEBI:16467', 'Chemical') :: ['Arg'] @entity69686 :: ('c|SUB|AGC||AGG', 'DNAMutation') :: ['AGC-->AGG'] @entity19434 :: ('MESH:D005177', 'Disease') :: ['FXIII deficiency', 'congenital FXIII deficiency']
@entity19434 :: (MESH:D005177,Disease) :: ['factor XIII deficiency']
