Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-A, non-B hepatitis, recently renamed as hepatitis C virus (HCV), accounts for over 90% of hepatitis cases worldwide associated with blood transfusions. Application of a recombinant-based enzyme immunoassay for the detection of antibodies to HCV to a sample of 500 male Saudi blood donors and 260 healthy Saudi pregnant women indicated that HVC is endemic in the Saudi population. Anti-HCV was detected in 28 (5.6%) of the blood donors and 12 (4.6%) of the pregnant women, for an overall frequency of 5.3% in healthy Saudi adults who had never received blood transfusions. This rate is at least 5 times higher than that reported for the US and Western Europe. Also assessed was the HCV rate in subsamples of Saudis considered at risk of this infection. Here, anti-HCV was detected in 22 (78.6%) hemophiliacs, 26 (33.3%) patients with thalassemia and sickle cell disease, 17 (26.1%) hemodialysis patients with renal failure, and 35 (15.9%) individuals with a sexually transmitted disease. The prevalence of anti-HBc ranged from 28% in blood donors to 46% in hemophiliacs. The significantly higher prevalence of HCV in patients with sexually transmitted diseases than in blood donors suggests that this disease is transmitted through heterosexual contact as well as blood transfusions. Given the high baseline level of HCV infection in the Saudi population and the possibility of serious sequelae (e.g., chronic active hepatitis, cirrhosis, and hepatocellular carcinoma), routine anti-HCV screening of blood donations is urged.
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PMID:Hepatitis C virus antibodies in high-risk Saudi groups. 177 46

Seventeen of 73 (23.3%) multiply transfused patients with thalassaemia major (age range, 1-39 years) tested positive for antibody to hepatitis C virus (anti-HCV). Eleven of the 24 patients regularly transfused in countries outside Britain were anti-HCV seropositive; only six of the 49 regularly transfused in Britain were seropositive. The incidence of anti-HBs and anti-HBc was similar to that of anti-HCV in both the British and foreign patients. The anti-HCV seropositive patients showed significantly higher plasma aspartate aminotransferase activities (AST), mean (SD) 10.2 (70.3) U/l, and serum ferritin concentrations, 4067 (2708) micrograms/l, than the anti-HCV seronegative patients (AST, 33.9 (15.6) U/l; serum ferritin 2051 (2092) U/l), respectively. Among the 36 patients who had earlier undergone liver biopsy 10 of 21 with histological features of chronic active hepatitis or cirrhosis, or both, were seropositive for anti-HCV whereas only one of 15 without histological evidence of chronic viral hepatitis was seropositive for anti-HCV. It is concluded that HCV is a major cause of chronic hepatitis in patients with thalassaemia major and is associated with raised AST activity and serum ferritin concentration compared with patients seronegative for anti-HCV.
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PMID:Antibody to hepatitis C virus in multiply transfused patients with thalassaemia major. 211 95

We studied 29 patients with thalassaemia major who had received intensive chelation for between 6.2 and 8.8 years. All patients had normal oral glucose tolerance tests before subcutaneous chelation therapy was introduced and 22 of 29 patients had normal liver function tests. At the end of the period of study 12 patients still had normal oral glucose tolerance (7 with normal liver function tests and 5 with chronic active hepatitis). On the other hand, 11 patients had developed impaired glucose tolerance tests (3 patients had normal liver function tests, 5 with chronic active hepatitis and 3 with cirrhosis), and 6 patients had developed frank diabetes mellitus (one with chronic active hepatitis and 5 with cirrhosis). Patients with chronic active hepatitis showed 91% positivity for one or more hepatitis B markers whilst all patients with cirrhosis were positive. Ferritin levels before subcutaneous chelation in patients with normal oral glucose tolerance tests were lower than in those patients with abnormal oral glucose tolerance or diabetes (P less than 0.05) but none had normal serum ferritin levels. In addition, a positive correlation was found between glucose area under the curve after chelation therapy and serum ferritin levels (r = 0.47, P less than 0.01). It is apparent that long term chelation therapy does not prevent the development of abnormal oral glucose tolerance in chronically transfused patients. More intensive chelation therapy is needed to prevent tissue damage. Chronic liver disease may have an important role to play in the deterioration of glucose tolerance.
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PMID:The development of diabetes mellitus and chronic liver disease in long term chelated beta thalassaemic patients. 354 13

Serum ferritin, an index of iron stores, was studied in 60 patients with porphyria cutanea tarda (PCT), in 21 patients who had other liver diseases without siderosis (cirrhosis [LC] and chronic active hepatitis [CAH]), and in 32 patients with associated liver siderosis (alcoholic LC, LC and CAH in minor thalassemia). Ferritin levels were higher in patients with porphyria than in healthy controls and patients without liver siderosis (P less than 0.001), whereas no statistical difference was observed between patients with porphyria and those with liver siderosis. Because iron removal is considered the treatment of choice for PCT, some patients with PCT underwent phlebotomy and others received chelating therapy with subcutaneous infusion of deferoxamine. Follow-up of the patients showed a correlation between serum ferritin level and urinary porphyrin excretion; when the clinical and biochemical syndrome became normal, serum iron and ferritin had fallen to normal values (t test pair data analysis before and after: P less than 0.001 in each group). No appreciable difference was found between controls and patients with PCT whose conditions had been normalized, irrespective of the chronic liver damage always present in PCT. Our results suggest that serum ferritin increase in PCT is related more to liver iron overload than to liver damage, and ferritin follow-up is recommended to indicate the exhaustion of hepatic iron stores during iron depletion therapy, as well as to detect an early replenishment after remission.
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PMID:Serum ferritin in the assessment of liver iron overload and iron removal therapy in porphyria cutanea tarda. 394 Dec 93

Some parameters of iron metabolism in 26 patients with porphyria cutanea tarda (PCT) which is often associated with mild iron overload and hepatic siderosis, are studied. Serum iron, percent transferrin saturation and ferritin were pathologically increased. Statistical comparisons were performed between PCT patients and healthy controls, liver disease patients (cirrhosis, chronic active hepatitis) and patients with associated liver siderosis (alcoholic cirrhosis, cirrhosis and chronic active hepatitis in thalassemia). Ferritin levels are higher in patients with porphyria than in healthy controls (p less than 0,001) and in patients without liver siderosis (p less than 0,001). No statistical difference is observed between patients with porphyria and patients with siderosis. A significant decrease in ferritin levels is registered after venesection therapy. The conclusion is drawn that serum ferritin increase in PCT is related to hepatic iron store amounts rather than hepatic necrosis. It is assumed that ferritin follow-up during phlebotomy therapy and also during remission is useful to indicate the exhaustion or an early replenishment of hepatic iron stores.
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PMID:[Determination of serum ferritin in porphyria cutanea tarda. A reliable sign of hepatic siderosis]. 670 23

A non-specific iron fraction, not bound to transferrin, has been looked for in the sera of 42 never-transfused patients with beta-thalassaemia trait, 17 of whom had chronic active hepatitis, negative for HBV infection or alcohol abuse. Non-specific iron was found only in the sera of those patients with beta-thalassaemia trait plus chronic active hepatitis who had complete transferrin saturation, high serum ferritin levels and urinary iron excretion and a high degree of hepatic siderosis. In view of the known toxicity of non-transferrin iron, we suggest that this non-transferrin iron fraction may be responsible for the liver damage in these patients. Furthermore, the positive correlation between the presence and the amount of non-transferrin iron and the levels of serum ferritin suggests that this fraction is a sensitive indicator of iron-induced toxicity when severe iron overload slowly develops in patients with beta-thalassaemia trait even in the absence of any iron administration.
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PMID:Non-specific iron in patients with beta-thalassaemia trait and chronic active hepatitis. 725 13

The systematic screening of 253 children with transfusion-dependent homozygous beta-thalassaemia revealed a high incidence of hepatitis B virus markers. The highest frequencies of hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) were found in the group of patients with the smallest number of transfusions, while the highest frequency of antibody to hepatitis B surface antigen (anti-HBs) was detected in the patients who had had the largest number of transfusions. Follow-up of these patients showed (a) a high incidence of acute hepatitis B, which was mainly subclinical; (b) normal hepatitis B surface antigen clearance and normal antibody to hepatitis B surface development; and (c) a high frequency of increased transaminase values for over six months. In all the subjects with persistently high transaminase, histological examination revealed chronic persistent hepatitis or chronic active hepatitis. Apart from two cases of chronic active hepatitis with no B virus markers, and two cases of chronic persistent hepatitis with HBsAg and anti-HBc in the serum, all these subjects were anti-HBs positive but HGsAg and anti-HBc negative.
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PMID:Chronic liver disease in transfusion-dependent thalassaemia: hepatitis B virus marker studies. 743 Mar 60

We studied 95 patients and their relatives with the classical salt wasting (SW) and simple virilizing (SV) form of CAH. SSCP/heteroduplex analysis allowed fast and efficient screening for the most common 21-hydroxylase mutations (e.g. deletions, splice site mutation in intron 2 (bp 656), Ile172Asn mutation in exon 4) and determination of the relative intensities of CYP21A and CYP21B genes. The splice site mutation in intron 2 was found as the most frequent cause of 21-hydroxylase deficiency (35% of our patients). There is a strong genetic association between the mutation in intron 2 and the SW form of CAH. On the other hand, about 20% of our patients with the intron 2 mutation have the SV phenotype. Interestingly, homozygous splice site mutations in intron 2 were also detected in some parents or other relatives with no phenotypic changes typical for CAH (clinical evaluation, steroid hormone levels). In those patients with SV-CAH and especially in the relatives with the homozygous intron 2 mutation and an unaffected phenotype, the splice site mutation could be "leaky". mRNA-splicing in the adrenal cortex should result in a high degree of normal mRNA species. This is in contrast to in vitro expression studies of CYP21B genes containing the intron 2 mutation, performed by other groups. However, the results of in vitro expression studies are not always reflecting the in vivo conditions in the adrenal cortex. This situation is in good agreement with the variable degree of normal spliced mRNA and different phenotypic severity in intron mutations found in thalassemia.
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PMID:Divergence between genotype and phenotype in relatives of patients with the intron 2 mutation of steroid-21-hydroxylase. 758 99

The purpose of this study was to determine whether interferon-alfa (IFN-alpha) therapy benefits patients with transfusion-dependent thalassemia and chronic active hepatitis C, and whether their iron burden modifies the response to this therapy. We conducted a controlled trial of recombinant IFN-alpha (3 million units per square meter of body surface area, three times a week for 15 months) in 65 patients with thalassaemia major and chronic active hepatitis C; 14 of them were untreated control subjects. In 21 of the 51 treated patients, alanine aminotransferase values returned to normal within 6 months, and hepatitis C virus ribonucleic acid was no longer detected in serum; no changes were detected among control subjects. The response to IFN-alpha therapy was inversely related (p < 0.002) to the liver iron burden as assessed by atomic absorption, the histologic semiquantitative method, or both methods. During 3 years of follow-up, two responder patients had relapses. We conclude that IFN-alpha represents a useful therapeutic option for children with transfusion-dependent thalassemia and chronic active hepatitis C with a mild to moderate iron burden.
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PMID:Effect of iron overload on the response to recombinant interferon-alfa treatment in transfusion-dependent patients with thalassemia major and chronic hepatitis C. 802 61

Hepatitis C virus (HCV) is responsible for the majority of cases of post transfusion non-A non-B (NANB) hepatitis in thalassaemia major (TM). Fifteen multi-transfused TM patients with serological, biochemical, histological and molecular biological evidence of HCV infection have been treated for six months with recombinant alpha interferon (IFN). Eleven (73%) responded, 8 (53%) had complete response (CR), 3 (20%) partial response (PR) and 4 (27%) did not respond (NR) to IFN. Natural killer (NK) cell activity 24 hours after the first dose of IFN was significantly increased in responders as compared to non-responders. Liver histology showed an overall reduction of portal inflammation and periportal necrosis in the responding patients. HCV RNA disappeared from serum in 8 (15) responders and partial responders. Non responders remained positive. HCV RNA was tested and found to be positive in liver tissue material in 7 patients, five of those were re-tested after IFN treatment. Two became negative (both CR) 3 remained positive despite biochemical response to IFN. The degree of induction of peripheral blood mononuclear cell 2'5' oligoadenylate synthetase messenger RNA (2-5 OAS mRNA), an enzyme induced by IFN, after the first dose of IFN did not correlate with response neither was any significant interaction with cytokines observed; tumour necrosis factor (TNF), interleukin-1. (IL-1) and CD4:CD8 ratios did not change. We conclude that IFN should be given to all TM patients with chronic active hepatitis due to HCV.
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PMID:Recombinant alpha 2B interferon (IFN) in the treatment of chronic hepatitis C disease in thalassaemia major (TM). 839 33


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