1/22. Is the coexistence of mutations in the genes of factor v and MTHFR a predisposing factor for massive skin necrosis due to loxoscelism?A 28-year-old previously healthy man was diagnosed as having an extensive necrotic lesion of his calf due to loxoscelism. One year later he was diagnosed as having co-inheritance of mutations in factor v and methyl tetrahydrofolate reductase (MTHFR). This is the first report of a possible etiologic connection between loxoscelism necrotic lesions and thrombogenic diseases.- - - - - - - - - - ranking = 1keywords = mutation (Clic here for more details about this article) |
2/22. Unusual complications of warfarin therapy: skin necrosis and priapism.skin necrosis and priapism are unusual complications of warfarin therapy. We report a teenager with warfarin-associated skin necrosis and priapism who was subsequently found to be a compound heterozygote for protein c deficiency and a heterozygote for the factor v Leiden mutation.- - - - - - - - - - ranking = 0.2keywords = mutation (Clic here for more details about this article) |
3/22. Severe digital necrosis in an elderly patient with heterozygous factor v Leiden mutation.We report an 81-year-old female with a heterozygous factor v Leiden mutation who developed purpura fulminans. Digital necrosis, a characteristic clinical feature of purpura fulminans was prominent. purpura fulminans is more common in children and adult cases are rare. Of eight reported cases of purpura fulminans resulting from a heterozygous factor v Leiden mutation recorded in the literature, only two were in adults: 40 and 42 years of age, respectively. This is the first report of this condition arising in a patient in her eighties.- - - - - - - - - - ranking = 1.2keywords = mutation (Clic here for more details about this article) |
4/22. Fatal submassive hepatic necrosis associated with tyrosine-methionine-aspartate-aspartate-motif mutation of hepatitis b virus after long-term lamivudine therapy.We present a case of infection with lamivudine-resistant mutant hepatitis b virus (HBV) that fatally exacerbated hepatitis following the emergence of HBV with mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) motif in an immunocompetent patient who was receiving long-term lamivudine therapy. Restriction fragment length polymorphism analysis showed that the YMDD-motif mutant was the predominant form of circulating HBV at the time of the fatal exacerbation, and a necropsy specimen of the liver revealed submassive hepatic necrosis without steatosis.- - - - - - - - - - ranking = 1keywords = mutation (Clic here for more details about this article) |
5/22. leigh disease: clinical, neuroradiologic, and biochemical study of three new cases with cytochrome c oxidase deficiency.Three cases of leigh disease are described. In all three, symptoms began in the first months of life, with muscle hypotonia, lactic acidosis, and psychomotor delay. The diagnosis was made on the basis of the clinical characteristics, biochemical abnormalities, and typical brain magnetic resonance imaging with symmetric lesions suggesting bilateral necrosis at the level of the basal ganglia and of the midbrain. Cytochrome c oxidase (complex IV of the mitochondrial respiratory chain) deficiency was demonstrated in muscle tissue in all patients and confirmed in skin fibroblasts in patient 3. A genetic heterogeneity was present in these patients since only one had a SURF-1 gene mutation. The clinical, biochemical, and neuroradiologic aspects are discussed. Finally, the finding of facial dysmorphisms in the cytochrome c oxidase deficiency observed in one of the described cases is of extreme interest; to our knowledge, this association has never been reported in the literature.- - - - - - - - - - ranking = 0.2keywords = mutation (Clic here for more details about this article) |
6/22. Cutaneous necrosis revealing the coexistence of an antiphospholipid syndrome with acquired protein s deficiency, factor v Leiden and hyperhomocysteinemia.We report an exceptional case of cutaneous necrosis due to the coexistence of 4 thrombophilic factors, inherited and acquired. We would like to draw attention to these unrecognized associations. CASE REPORT: A 72-year-old woman was admitted with a 5 month history of necrotic nonhealing, painful ulcer of both legs and recently a purple toe. She had a history of 3 deep venous thromboses of the leg complicated by pulmonary embolism. A skin biopsy of the ulcer and purple toe showed only thrombosis in the dermal vessel. Laboratory findings showed a circulating lupus anticoagulant, positive anticardiolipin antibodies, antinuclear antibodies (1/320 dilution) and an anti Sm. Moreover, activated protein c resistance associated with factor v Leiden mutation and hyperhomocysteinemia was found; protein S was transiently low. With iloprost, oral anticoagulant, vitamin B12 and folic acid, the evolution was good, with healing of ulcer. COMMENTS: cutaneous necrosis can reveal hypercoagulable states, sometimes complex. We find 4 thrombophilic factors in our case, i.e. antiphospholipid antibodies, factor v Leiden, protein s deficiency and hyperhomocysteinemia. This is exceptional but highlights the role of several constitutional and acquired thrombophilic factors in the genesis of thrombosis. Extended protein C pathway disturbances could explain the mechanism that leads to cutaneous necrosis, in this patient, with an antiphospholipid syndrome. This case shows that it is necessary in some circumstances to make a complete hemostatic laboratory search to detect several thrombophilic factors. If they are present they can justify an oral anticoagulant treatment and a familial screening.- - - - - - - - - - ranking = 0.2keywords = mutation (Clic here for more details about this article) |
7/22. Chronic disseminated intravascular coagulation and childhood-onset skin necrosis resulting from homozygosity for a protein C Gla domain mutation, Arg15Trp.A toddler of Haitian descent presented with an 18-month history of chronic consumption coagulopathy, followed by catastrophic skin necrosis. protein c deficiency (1% to 3% of control) was noted by functional assay; chromogenic assay and antigen levels were 30% of control. plasma infusion abrogated the disseminated intravascular coagulation-like state. The authors identified a homozygous mutation, C1432T, resulting in a missense, Arg15Trp, in the gamma-carboxyglutamate domain of the protein. Chronic consumption coagulopathy without purpura fulminans or venous thrombosis is a rare presentation of defective protein C pathway. The result of this mutation is a mixed type I (low antigen) and type II (low function) phenotype.- - - - - - - - - - ranking = 1.2keywords = mutation (Clic here for more details about this article) |
8/22. mutation of the core region of HBV-dna and submassive hepatic necrosis in patients with anti-HBe-positive chronic hepatitis B.Three patients with submassive hepatic necrosis developed acute liver failure during the severe reactivation of chronic hepatitis B. The activity of hepatitis B virus (HBV) dna polymerase increased in all three patients immediately before the onset of hepatic failure. Liver biopsy specimens obtained before and after the episode of submassive hepatic necrosis showed progression to advanced liver cirrhosis. The nucleotide sequences of the precore and core regions of HBV-dna were investigated in two of the three patients and in another two patients with piecemeal and bridging necrosis. The nucleotide and amino acid sequences of the HBV-dna core region changed after reactivation in the the two patients with submassive hepatic necrosis, while the sequences in the other two patients with piecemeal necrosis remained unchanged before and after reactivation. These results suggest that the antigenicity of the HBV-dna core region may have been changed before and after severe reactivation. Due to mutation at the core region, a different type of epitope would be expressed on the hepatocytes after submassive hepatic necrosis, which would not be a target for the cytotoxic T cell. This was evident by the continuation of the normal serum GPT for 5 and 9 years, respectively.- - - - - - - - - - ranking = 0.2keywords = mutation (Clic here for more details about this article) |
9/22. Bilateral striatal necrosis associated with a novel mutation in the mitochondrial ND6 gene.We report the molecular findings in two independent patients presenting with progressive generalized dystonia and bilateral striatal necrosis in whom we have identified a mutation (T14487C) in the mitochondrial ND6 gene. The mutation is heteroplasmic in all samples analyzed, and it fulfills all accepted criteria of pathogenicity. Transmitochondrial cell lines harboring 100% mutant mitochondrial dna showed a marked decrease in the activity of complex I of the respiratory chain supporting the pathogenic role of T14487C.- - - - - - - - - - ranking = 1.2keywords = mutation (Clic here for more details about this article) |
10/22. Mesenteric thrombosis causing short bowel syndrome in nephrotic syndrome.Nephrotic patients are at risk of developing venous and arterial thrombotic complications. pulmonary embolism due to affected deep leg veins is by far the most common event. Renal or cerebral vein thromboses have been described. Thrombosis of arterial vessels is less frequent. Mesenteric infarction is a rare but severe complication in patients with nephrotic syndrome (NS). We report a 7-year-old boy with a steroid-dependent (SD) NS and a homozygous mutation of methylenetetrahydrofolate reductase, increasing the risk of thromboembolic events. He developed a thrombosis of his superior mesenteric artery during his ninth relapse, which was responsible for a necrosis of 240 cm of his small bowel, necessitating resection of necrotic parts and double external ostomy diversion. Remission was achieved with pulse prednisolone therapy. Corticoids were reduced over 4 months progressively. Oral cyclosporin A (CyA) was initiated for long-term treatment. Due to a short bowel syndrome with severe malabsorption, even oral administration of 22.5 mg/kg per day CyA did not lead to sufficient plasma levels. Intravenous cyclophosphamide pulse therapy over 6 months led to a complete remission. No relapse occurred over a period of more than 5 months after the last cyclophosphamide pulse. Anticoagulation and screening for increased susceptibility for thrombotic events are necessary in every nephrotic patient. Intravenous cyclophosphamide pulse therapy is a useful alternative in SDNS with impaired intestinal absorption of applied immunosuppressive drugs.- - - - - - - - - - ranking = 0.2keywords = mutation (Clic here for more details about this article) |
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