1/204. (TA)8 allele in the UGT1A1 gene promoter of a Caucasian with Gilbert's syndrome.BACKGROUND AND OBJECTIVE: Gilbert's syndrome, a chronic non-hemolytic unconjugated hyperbilirubinemia, is caused by a reduction in the activity of hepatic bilirubin UDP-glucuronosyltransferase (UGT1A1). This reduction has been shown to be due to a polymorphism in the promoter region of the UGT1A1 gene. The presence of seven thymine adenine (TA) repeats reduces the efficiency of transcription of the UGT1A1 gene. To elucidate the genetic background of a patient affected by Gilbert's syndrome, we collected blood samples from family members for the analysis of the A(TA)nTAA motif in the promoter region of the UGT1A1 gene. DESIGN AND methods: Analysis of the A(TA)nTAA motif in the promoter region of the UGT1A1 gene was performed by PCR. Estimation of UGT1A1 promoter containing the variable (TA) repeats was performed by using a luciferase reporter system. RESULTS: Three different genotypes were identified due to the presence of (TA)6, (TA)7 and (TA)8 repeats. The production of luciferase decreases in inverse relation to the number of repeats. INTERPRETATION AND CONCLUSIONS: The (TA)7 polymorphism, associated with Gilbert syndrome, is the only allele found up to now in white populations, while two other variants (TA)5 and (TA)8 have been identified in black populations. We describe here the first case of a subject affected by Gilbert's syndrome who is heterozygous for the (TA)8 allele in the promoter region of the UGT1A1 gene. This polymorphism, as well as the (TA)7 one, is associated with an increased level of bilirubin and a significant reduction of transcription activity of the UGT1A1 gene.- - - - - - - - - - ranking = 1keywords = hemolytic (Clic here for more details about this article) |
2/204. An inherited disorder of lymphocyte apoptosis: the autoimmune lymphoproliferative syndrome.The autoimmune lymphoproliferative syndrome (ALPS) affords novel insights into the mechanisms that regulate lymphocyte homeostasis and underlie the development of autoimmunity. This syndrome arises early in childhood in persons who inherit mutations in genes that mediate apoptosis, or programmed cell death. The timely deletion of lymphocytes is a way to prevent their accumulation and the persistence of cells that can react against the body's own antigens. In ALPS, defective lymphocyte apoptosis permits chronic, nonmalignant adenopathy and splenomegaly; the survival of normally uncommon "double-negative" CD3 CD4- CD8- T cells; and the development of autoimmune disease. Most cases of ALPS involve heterozygous mutations in the lymphocyte surface protein Fas that impair a major apoptotic pathway. Detailed immunologic investigations of the cellular and cytokine profiles in ALPS show a prominent skewing toward a T-helper 2 phenotype; this provides a rational explanation for the humoral autoimmunity typical of patients with ALPS. Prospective evaluations of 26 patients and their families show an ever-expanding spectrum of ALPS and its major complications: hypersplenism, autoimmune hemolytic anemia, thrombocytopenia, and neutropenia. Defective apoptosis may also contribute to a heightened risk for lymphoma.- - - - - - - - - - ranking = 1keywords = hemolytic (Clic here for more details about this article) |
3/204. Anaemia, thrombocytopenia and coagulopathy due to occult diffuse infantile haemangiomatosis of spleen and pancreas.Diffuse infantile haemangiomatosis of the spleen is a very rare lesion. Large haemangiomas may cause trapping of platelets and coagulation disorders known as Kasabach-Merrit syndrome. We here report the case of an infant with splenic and pancreatic haemangiomatosis presenting with life-threatening thrombocytopenia, anaemia and intravascular coagulation. Diagnosis was hampered by reactive erythroblastosis and non-conclusive radiological findings. While treatment with corticosteroids was ineffective, administration of antithrombin iii improved coagulation parameters. After splenectomy the child recovered promptly and has remained free of disease for 3 years to date. CONCLUSION: Occult visceral haemangiomatosis without visible cutaneous haemangiomas should be included in the differential diagnosis of thrombocytopenia, anaemia and consumption coagulopathy. antithrombin iii treatment may be considered to overcome bleeding problems in patients with Kasabach-Merrit syndrome.- - - - - - - - - - ranking = 2.5003078363919keywords = anaemia (Clic here for more details about this article) |
4/204. Familial Evans syndrome: a report of an affected sibship.PURPOSE: This report describes the clinical course of three siblings, all of whom had Evans syndrome in childhood. patients: The coexistence of autoimmune hemolytic anemia and thrombocytopenia, in the absence of a known underlying cause, led to the diagnosis of Evans syndrome in a 4-month-old girl and subsequently in her two brothers when they were 4 and 13 years old. RESULTS: The 4-month-old girl had a life-threatening relapsing course unresponsive to corticosteroids, intravenous gamma-globulin, thymectomy, and cyclophosphamide. She eventually responded to splenectomy. Her two brothers had milder disease that responded to corticosteroids. Cytogenetic analyses revealed the presence of a familial Y;15 translocation in all three children and their father. CONCLUSION: There are few reported cases of familial Evans syndrome, and they are usually associated with an inherited congenital abnormality. We report the unusual finding of three siblings with the disease and no known congenital abnormality.- - - - - - - - - - ranking = 1keywords = hemolytic (Clic here for more details about this article) |
5/204. pregnancy in bone marrow failure syndromes: diamond-Blackfan anaemia and Shwachman-diamond syndrome.pregnancy in bone marrow failure syndromes has risk to mother and fetus. There are fewer than 30 reports of cases with diamond-Blackfan anaemia (DBA), and none with Shwachman-diamond syndrome (SD). We report two DBA and one SD cases. One DBA mother received transfusions intra-partum, and the other only post-partum. Both required caesarean sections (C-sections) for failure of labour to progress and severe pre-eclampsia respectively. Both subsequently resumed pre-pregnancy steroid-induced control of anaemia. approximately 40% of DBA pregnancies required maternal transfusions; 25% delivered by C-section. The SD patient also had Ehlers-Danlos (ED) syndrome and urticaria pigmentosa (UP). Her blood counts were adequate until week 38, when the platelet count dropped and a C-section was performed. pregnancy management in marrow failure disorders requires obstetricians with expertise in high-risk pregnancies, and haematologists with experience with marrow failure syndromes.- - - - - - - - - - ranking = 7.5009235091758keywords = anaemia (Clic here for more details about this article) |
6/204. Congenital hypoplastic anaemia in a patient with a new multiple congenital anomalies-mental retardation syndrome.We report on a girl with congenital hypoplastic anaemia, "coarse" face, generalized hypertrichosis with scalp hypotrichosis, short fifth finger, hypoplastic toenails, and mental retardation. A sister of the proposita, who died at the age of 1 year, had severe congenital anaemia, hypoplastic fingernails, low birth weight, failure to thrive, and repeated upper respiratory tract infections. Based on family history, we suspect that hypoplastic anaemia and the same multiple congenital anomalies-mental retardation syndrome (MCA/MR) were also present in this sister. To the best of our knowledge, this patient represents the first report of congenital hypoplastic anaemia and such a complex MCA/MR syndrome, probably inherited as an autosomal recessive trait.- - - - - - - - - - ranking = 10.001231345568keywords = anaemia (Clic here for more details about this article) |
7/204. delayed diagnosis of glucagonoma syndrome.The classical presentations of necrolytic migratory erythema associated with alpha cell pancreatic tumour have been well documented. In addition, the occurrence of extracutaneous hallmarks of this disease such as weight loss, diabetes, anaemia, stomatitis and diarrhoea have been described in various reports. Here we report three cases with glucagonoma syndrome. Early detection is important in view of the malignant course of the disease. However, diagnosis is sometimes complicated by the fact that some patients may fail to show the characteristic feature of glucagonoma syndrome.- - - - - - - - - - ranking = 1.250153918196keywords = anaemia (Clic here for more details about this article) |
8/204. A microdeletion in 19q13.2 associated with mental retardation, skeletal malformations, and diamond-Blackfan anaemia suggests a novel contiguous gene syndrome.diamond-Blackfan anaemia (DBA) is a constitutional red blood cell hypoplasia which may be associated with a variety of developmental abnormalities. A gene for DBA was recently mapped to chromosome 19q13.2 and subsequently cloned. Analysis of 19q marker alleles in dna of sporadic DBA cases showed de novo microdeletions in three patients also presenting with mental retardation. We have studied one of these patients and characterised the deletion by fluorescence in situ hybridisation (FISH) to extended dna fibres. The deletion was shown to be continuous over a 3.2 Mb region and the fibre-FISH analysis showed both chromosomal breakpoints. In combination, the clinical and molecular findings suggest a contiguous gene syndrome with a gene locus for mental retardation and, probably, skeletal malformations included in the deletion.- - - - - - - - - - ranking = 6.2507695909798keywords = anaemia (Clic here for more details about this article) |
9/204. Immune thrombocytopenia and hemolytic anemia as a presenting manifestation of hodgkin disease.A very unusual clinical presentation of hodgkin disease with immune thrombocytopenia and autoimmune hemolytic anemia is reported. A 6.5-year-old boy presented with thrombocytopenia, Coombs' positive hemolytic anemia, and multiple small posterior cervical lymph nodes. After a course of high-dose methylprednisolone therapy with a diagnosis of Evans syndrome, complete response for thrombocytopenia and partial response for anemia was achieved. Six weeks later there was a sudden increase in the size of left posterior cervical lymph nodes and a biopsy was compatible with hodgkin disease, mixed cellularity type. The child was successfully treated with chemotherapy and radiation therapy. He has been off therapy for 28 months and has no clinical or laboratory evidence of autoimmune cytopenia. A combination of immune thrombocytopenia and autoimmune hemolytic anemia may be associated with hodgkin disease. The recognition of this clinical picture as a complication of hodgkin disease has important implications. This complication appeares to be managed best by the definitive treatment of hodgkin disease.- - - - - - - - - - ranking = 7keywords = hemolytic (Clic here for more details about this article) |
10/204. Characterization of a novel mitochondrial dna deletion in a patient with a variant of the Pearson marrow-pancreas syndrome.We have recently diagnosed a patient with anaemia, severe tubulopathy, and diabetes mellitus. As the clinical characteristics resembled Pearson marrow-pancreas syndrome, despite the absence of malfunctioning of the exocrine pancreas in this patient, we have performed dna analysis to seek for deletions in mtDNA. dna analysis showed a novel heteroplasmic deletion in mtDNA of 8034bp in length, with high proportions of deleted mtDNA in leukocytes, liver, kidney, and muscle. No deletion could be detected in mtDNA of leukocytes from her mother and young brother, indicating the sporadic occurrence of this deletion. During culture, skin fibroblasts exhibited a rapid decrease of heteroplasmy indicating a selection against the deletion in proliferating cells. We estimate that per cell division heteroplasmy levels decrease by 0.8%. By techniques of fluorescent in situ hybridisation (FISH) and mitochondria-mediated transformation of rho(o) cells we could show inter- as well as intracellular variation in the distribution of deleted mtDNA in a cell population of cultured skin fibroblasts. Furthermore, we studied the mitochondrial translation capacity in cybrid cells containing various proportions of deleted mtDNA. This result revealed a sharp threshold, around 80%, in the proportion of deleted mtDNA, above which there was strong depression of overall mitochondrial translation, and below which there was complementation of the deleted mtDNA by the wild-type dna. Moreover, catastrophic loss of mtDNA occurred in cybrid cells containing 80% deleted mtDNA.- - - - - - - - - - ranking = 1.250153918196keywords = anaemia (Clic here for more details about this article) |
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