1/8. Combined deficiency of factors II, VII, IX, and X (Borgschulte-Grigsby deficiency) in pregnancy.BACKGROUND: Combined deficiency of vitamin k-dependent coagulation factors (II, VII, IX, X) is an uncommon challenge for the expectant gravida. CASE: A 34-year-old primigravida had congenital combined deficiency of factors II, VII, IX, and X that were incompletely sensitive to vitamin k. She had an altered form of vitamin k-dependent factors that retained immunologic activity but lacked coagulant activity and the normal complement of gamma-carboxyglutamic acid residues. She required vitamin k supplementation throughout her life. After an uneventful pregnancy she had postpartum hemorrhage resulting from an episiotomy. Fresh frozen plasma was administered to achieve hemostasis. The remainder of her postpartum course was normal. CONCLUSION: Combined congenital deficiency of factors II, VII, IX, and X can be managed in pregnancy with the use of vitamin k and fresh frozen plasma.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
2/8. Inherited complete factor I deficiency associated with systemic lupus erythematosus, higher susceptibility to infection and low levels of factor H.Here we describe two new cases of complete deficiency of factor I (fI) in two sisters from a consanguineous Brazilian family. The eldest sibling (20-year-old) developed systemic lupus erythematosus (SLE) early during childhood while the youngest had been committed on several occasions owing to repeated infections although she was asymptomatic for auto-immune diseases. We also detected lower concentrations of C3 and factor B in both sisters. Biological functions dependent on complement activation such as the production of opsonins and killing of phagocytozed micro-organisms, chemotactic factors and haemolytic activity were all significantly reduced in both probands. Consistent with the absence of fI and low levels of fH, a deregulated production of C3b was observed by bidimensional electrophoresis in sera of both the probands.- - - - - - - - - - ranking = 0.45454545454545keywords = deficiency (Clic here for more details about this article) |
3/8. Hereditary human complement c3 deficiency owing to reduced levels of C3 mRNA.An 8-year-old son (L.A.S.) of consanguineous parents, presented recurrent bacterial infections, vasculitis and extremely low levels of serum C3 (0.15 microg/ml). The classical and alternative pathway haemolytic activities and the generation of opsonins and chemotactic factors derived from the activation of the complement system were markedly affected in the proband's serum. An in vitro addition of purified C3 restored the classical pathway-dependent haemolytic activity of his serum. Autoradiographs of the proband's lipopolysaccharide (LPS)-stimulated and 35S-labelled fibroblast supernatants after that the SDS-PAGE revealed no C3 alpha or beta chains. The amount of C3 mRNA synthesized by the proband's fibroblasts, as evaluated by reverse transcription-polymerase chain reaction (RT-PCR) assays, was greatly reduced.- - - - - - - - - - ranking = 0.36363636363636keywords = deficiency (Clic here for more details about this article) |
4/8. Management of splenic trauma in the pediatric hemophiliac patient: Case series and review of the literature.In July and August 1998, 3 patients who attend the Hemophilia Treatment Center required emergency admission to the authors' hospital for management of hemorrhagic shock caused by splenic injury. Computed tomography was used to diagnose and grade the splenic injuries, which ranged from II to IV on the organ injury scale. Two patients had Christmas disease (factor ix deficiency) and were treated with splenorrhaphy and factor ix replacement. One patient who has severe von Willebrand disease (Type 3) had grade II splenic injury that required splenectomy to secure hemostasis. The coagulopathic deficiency was aggressively treated in each patient. All patients required operative intervention with attempted splenorrhaphy. All patients survived their operative experience, and none suffered a rebleeding episode. With correction of the coagulopathy throughout the perioperative period and local hemostatic control by operative techniques, salvage procedures for splenic injury were successful for 2 of these 3 patients.- - - - - - - - - - ranking = 0.18181818181818keywords = deficiency (Clic here for more details about this article) |
5/8. fibrinogen Saint-Germain I: a case of the heterozygous Aalpha GLY 12 --> VAL fibrinogen variant.A fibrinogen variant was suspected based on the results of routine coagulation tests in a 2-year-old asymptomatic child. Coagulation studies showed marked prolongation of both the thrombin and reptilase times, and discrepancy was noted between the level of plasma fibrinogen as measured by a kinetic versus immunological determination. family studies revealed that the father beared the same abnormality. Studies of purified fibrinogen revealed an impaired release of both fibrinopeptides by thrombin. Fibrin monomer polymerization and fibrin stabilization were normal. dna sequencing revealed a heterozygous G --> T point mutation in exon 2 of the gene coding for the Aalpha chain, which substituted a Gly for Val at position 12. Although the mutation is the same as in fibrinogen Rouen, fibrinogen Saint-Germain I shows a different fibrinopeptide release pattern and a mild factor v deficiency.- - - - - - - - - - ranking = 0.090909090909091keywords = deficiency (Clic here for more details about this article) |
6/8. Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin k-dependent blood coagulation factors.Hereditary combined deficiency of the vitamin k-dependent coagulation factors II, VII, IX, X, protein c, S and protein Z (VKCFD) is a very rare autosomal recessive inherited bleeding disorder. The phenotype may result from functional deficiency of either the gamma-glutamyl carboxylase (GGCX) or the vitamin k epoxide reductase (VKOR) complex. We report on the third case of VKCFD1 with mutations in the gamma-glutamyl carboxylase gene, which is remarkable because of compound heterozygosity. Two mutations were identified: a splice site mutation of exon 3 and a point mutation in exon 11, resulting in the replacement of arginine 485 by proline. Screening of 100 unrelated normal chromosomes by restriction fragment length polymorphism and denaturing high-performance liquid chromatography analysis excluded either mutation as a frequent polymorphism. Substitution of vitamin k could only partially normalize the levels of coagulation factors. It is suggested that the missense mutation affects either the propeptide binding site or the vitamin k binding site of GGCX.- - - - - - - - - - ranking = 146.91944915523keywords = carboxylase, deficiency (Clic here for more details about this article) |
7/8. Compound heterozygosity of novel missense mutations in the gamma-glutamyl-carboxylase gene causes hereditary combined vitamin k-dependent coagulation factor deficiency.Hereditary combined vitamin k-dependent (VKD) coagulation factor deficiency is an autosomal recessive bleeding disorder associated with defects in either the gamma-carboxylase, which carboxylates VKD proteins to render them active, or the vitamin k epoxide reductase (VKORC1), which supplies the reduced vitamin k cofactor required for carboxylation. Such deficiencies are rare, and we report the fourth case resulting from mutations in the carboxylase gene, identified in a Tunisian girl who exhibited impaired function in hemostatic VKD factors that was not restored by vitamin k administration. sequence analysis of the proposita did not identify any mutations in the VKORC1 gene but, remarkably, revealed 3 heterozygous mutations in the carboxylase gene that caused the substitutions Asp31Asn, Trp157Arg, and Thr591Lys. None of these mutations have previously been reported. family analysis showed that Asp31Asn and Thr591Lys were coallelic and maternally transmitted while Trp157Arg was transmitted by the father, and a genomic screen of 100 healthy individuals ruled out frequent polymorphisms. Mutational analysis indicated wild-type activity for the Asp31Asn carboxylase. In contrast, the respective Trp157Arg and Thr591Lys activities were 8% and 0% that of wild-type carboxylase, and their compound heterozygosity can therefore account for functional VKD factor deficiency. The implications for carboxylase mechanism are discussed.- - - - - - - - - - ranking = 244.50211222842keywords = carboxylase, deficiency (Clic here for more details about this article) |
8/8. A missense mutation in gamma-glutamyl carboxylase gene causes combined deficiency of all vitamin k-dependent blood coagulation factors.To identify potential mutations in the gamma-glutamyl carboxylase gene, the sequence of all exons and intron/exon borders was determined in 4 patients from a consanguineous kindred with combined deficiency of all vitamin k-dependent procoagulants and anticoagulants and results were compared with normal genomic sequence. All 4 patients were homozygous for a point mutation in exon 9 that resulted in the conversion of an arginine codon (CTG) to leucine codon (CGG) at residue 394. Screening of this mutation based on introduction of Alu I site in amplified fragment from normal allele but not from the mutated allele showed that 13 asymptomatic members of the kindred were heterozygous for the mutation. The mutation was not found in 340 unrelated normal chromosomes. The segregation pattern of the mutation which is the first reported in the gamma-glutamyl carboxylase gene fits perfectly with phenotype of the disorder and confirms the suggested autosomal recessive pattern of inheritance of combined deficiency of all vitamin k-dependent procoagulants and anticoagulants in this kindred. The mutated carboxylase protein expressed in drosophila cells was stable but demonstrated threefold reduced activity compared with WT carboxylase, confirming that the L394R mutation results in a defective carboxylase.- - - - - - - - - - ranking = 220.10644646012keywords = carboxylase, deficiency (Clic here for more details about this article) |