Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, a mild to moderate elevation in the plasma homocysteine (Hcy) level has been found to be an important risk factor for stroke. Homozygosity for a common mutation (C677T) in the gene encoding for the enzyme methylenetetrahydrofolate reductase (MTHFR) involved in Hcy metabolism has been associated with increased levels of Hcy. To determine the role of hyperhomocysteinemia in the pathogenesis of stroke in children with sickle cell disease (SCD), Hcy levels and C677T MTHFR genotype were determined in 40 patients homozygous for hemoglobin SS and compared with 197 healthy children. Eleven of 40 patients with SCD had a history of stroke. The prevalence of homozygosity for the C677T MTHFR variant was 5% in the patients with SCD. The median Hcy level was 5.8 micromol/L in the patients versus 5.4 micromol/L in the controls (Fisher's, P > 0.05). There was no correlation of Hcy levels with the MTHFR genotype in patients with SCD. In patients with SCD and stroke, the median Hcy level was 4.8 micromol/L versus 6.0 micromol/L in those without stroke (P = 0.44, Mann-Whitney rank sum test). There was no difference in the proportion of patients with SCD with or without stroke who were homozygous for the C677T MTHFR mutation (0/11 versus 2/29; Fisher's, P = 1.000). In conclusion, this study failed to demonstrate an elevation in plasma Hcy levels in children with SCD compared with normal controls. Furthermore, hyperhomocysteinemia did not seem to be a significant factor in the pathogenesis of stroke in children with SCD.
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PMID:Correlation of the C677T MTHFR genotype with homocysteine levels in children with sickle cell disease. 1052 53

Sickle cell disease (SCD) is relatively mild among Kuwaiti Arabs. However, an atypical subset of patients exists with frequent, severe vaso-occlusive crisis and osteonecrosis. The thermolabile variant of MTHFR, resulting from a C-->T mutation at nucleotide 677, has been shown to be associated with hyperhomocysteinemia, which is an important risk factor for premature vascular disease. We have screened an unselected group of 41 Kuwaiti SCD patients (33 SS and 8 Sbeta(0)-thal) attending the Hematology Clinic of Kuwait University Teaching Hospital for the MTHFR mutation, using a PCR-RFLP method. The patients were aged 2-41 years (mean of 12.8 +/- 8.6). One (2.4%) individual was homozygous for the mutation while 15 (36.6%) were heterozygous, giving an allele frequency of 20.7%. Twenty-one patients (14 SS and 7 Sbeta(0)-thal) were screened for osteonecrosis using MRI of the hip (spin-echo T1- and T2-weighted images). Seven (33.3%) had varying degrees of osteonecrosis, among whom the frequency of the 677 C-->T allele was 21.4%. The frequency was identical among those without osteonecrosis. Although the allele frequency is higher among our patients compared to American SS patients, our results do not suggest an association with osteonecrosis.
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PMID:Frequency of the 677 C-->T mutation of the methylenetetrahydrofolate reductase gene among Kuwaiti sickle cell disease patients. 1127 37

Elevated plasma homocysteine levels have been shown to be a risk factor for endothelial cell damage and thrombosis, which are implicated in sickle cell disease (SCD)-related vaso-occlusion. The aim of this study was to determine the prevalence of hyperhomocysteinemia in SCD. Fasting and postmethionine load (PML) homocysteine, red cell folate, and the MTHFR C677T mutation were determined in 77 patients with SCD and 110 African-American controls. Plasma methylmalonic acid and pyridoxine levels were determined in 54 patients and all controls. For analysis, the subjects were divided into two age groups (2-10 years and 10.1-21 years). In both age groups, median PML homocysteine levels were significantly elevated in patients with SCD compared with controls. Fasting homocysteine levels were elevated in patients with SCD versus controls only in those older than 10 years. Hyperhomocysteinemia was noted in 38% of patients versus 7% in controls. Folate levels were higher among patients than controls and showed a significant negative correlation with PML homocysteine levels in patients with SCD. Pyridoxine levels in patients with SCD were significantly lower than in controls and showed a negative correlation with PML homocysteine levels. Among patients with SCD, pyridoxine deficiency was more common (62%) among those with hyperhomocysteinemia compared with those with normal homocysteine levels (30%). Homozygosity for the MTHFR C677T mutation was rare. These data suggest that children with SCD have significant hyperhomocysteinemia, associated with pyridoxine and relative folate deficiencies.
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PMID:Hyperhomocysteinemia is associated with low plasma pyridoxine levels in children with sickle cell disease. 1214 86

Hereditary prothrombotic states of clinical importance include factor V Leiden, the prothrombin 20210A mutation, deficiencies of protein C, protein S, or antithrombin, sickle cell disease, and hyperhomocysteinemia. Major acquired prothrombotic states include cancer, myeloproliferative disorders, the antiphospholipid syndrome, and heparin-induced thrombocytopenia. Because most of the hereditary prothrombic states are not established risk factors for arterial thrombosis, routine laboratory testing in most patients with ischemic stroke should be limited to complete blood count, lupus anticoagulant, anticardiolipin antibodies, and plasma total homocysteine. Additional testing for factor V Leiden, prothrombin 20210A, antithrombin, protein C, and protein S may be indicated for patients under the age of 50 or those with paradoxical cerebral embolism. The treatment of acute ischemic stroke in patients with prothrombotic states is similar to that in patients without an identifiable prothrombotic condition, and may include antiplatelet agents, anticoagulants, or thrombolytic therapy in patients who otherwise meet eligibility criteria. The potential benefit of chronic anticoagulation therapy for the primary or secondary prevention of stroke in patients with prothrombotic states has not been addressed in controlled clinical trials. Specific therapeutic approaches for the prevention of stroke are established for patients with sickle cell disease, myeloproliferative disorders, and heparin-induced thrombocytopenia, and are under investigation for hyperhomocysteinemia and the antiphospholipid syndrome.
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PMID:Prothrombotic States that Predispose to Stroke. 1235 68

Although hypercoagulable states are most often associated with venous thrombosis, arterial thromboses are reported in protein S, protein C, and antithrombin III deficiencies, factor V Leiden and prothrombin gene mutations, hyperhomocysteinemia, dysfibrinogenemia, plasminogen deficiency, sickle cell disease, and antiphospholipid antibody syndrome.
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PMID:Coagulopathies and arterial stroke. 1261 91

Stroke affects up to 13 of 100,000 children, is more common in boys and African Americans, and is associated with considerable cognitive and psychiatric morbidity, as well as motor disability. Around half are hemorrhagic and half are ischemic. Underlying conditions include sickle cell disease, cardiac abnormalities, chromosomal abnormalities (eg, Down syndrome), and neurocutaneous conditions (eg, neurofibromatosis), but up to half the patients with ischemic stroke have no previously diagnosed condition. Although there is almost certainly an important genetic component to stroke risk, head trauma, infections, drugs and radiation appear to play an etiological role in some patients. The majority of the patients with infarction in an arterial distribution have associated cerebrovascular disease. Vascular pathologies include carotid or vertebrobasilar dissection, intracranial vasculopathy affecting the middle and anterior cerebral arteries, which is often transient, and moyamoya. Intermediate risk factors may include hypertension, hypoxia, and poor nutrition leading, for example, to iron deficiency and hyperhomocysteinemia. Some chronic conditions may directly influence the child's behavior and stroke recurrence risk, although large cohorts and randomized controlled trials will be needed before strategies for modification can be evidence-based.
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PMID:Risk factors for arterial ischemic stroke in childhood. 1516 88

Homocysteine has associations with both vitamin insufficiency and vascular complications, and its status is therefore of interest in sickle cell disease (SCD). However, information is limited, especially in adults. We studied plasma total homocysteine (tHcy) and three of its major modifiers, cobalamin, folate, and creatinine, in 90 adult patients with SCD and 76 control subjects. The patients had higher tHcy levels than did controls (P = 0.03) and had elevated tHcy more often (20% vs. 3%, P = 0.0005). None of the hyperhomocysteinemic patients had low cobalamin or folate levels; on the contrary, patients with SCD had high folate levels more often than control subjects (32% vs. 7%; P < 0.0001). Although serum creatinine values were lower in SCD patients than in control subjects (P = 0.03), high levels also tended to occur more often (8% vs. 1%; P = 0.054). Most importantly, creatinine levels correlated significantly with tHcy (P < 0.0001) and logistic regression analyses showed creatinine to be the only significant predictor of high tHcy levels in SCD (P = 0.01). Our results show that hyperhomocysteinemia affects 20% of adults with SCD despite routine folate supplementation and is independent of folate and cobalamin status. Creatinine was the major identifiable influence on tHcy, but renal insufficiency explained only 4 of the 18 elevated tHcy levels. Longitudinal studies will be needed to determine whether the frequent hyperhomocysteinemia of SCD influences the vascular complications in SCD. If reducing tHcy becomes advisable, then interventions other than folate therapy will be needed.
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PMID:Mild hyperhomocysteinemia in adult patients with sickle cell disease: a common finding unrelated to folate and cobalamin status. 1516 75

The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches for the implementation of guidelines and their use in high-risk populations.
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PMID:Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. 1697 25

The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches for the implementation of guidelines and their use in high-risk populations.
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PMID:Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. 1653 23

Most ophthalmologic disorders secondary to hypercoagulabe state are due to the confluence of congenital and adquired factors. A systematic workup is mandatory. Most of congenital coagulation disorders cause venous trombosis and are inherited autosomal dominantly. In order of frequency these are factor V Leiden mutation (activated protein C resistance), G20210A mutation of the prothrombin gen and protein C, protein S, and antithrombin III deficiencies. Sickle cell anemia can determine arerial and venous thrombosis. In relation with arterial occlusion, the markers most frequently involved are homcysteine fasting levels and the markers of antiphospholipid antibody syndrome. Both of them can also determine venous thrombosis. Several acquired factors can lead to hypoercoagulable state, especially hyperhomocysteinemia, antiphospholipid antibody syndrome, hepatic disease, alcohol and tobacco intake, oral contraceptives, immobilization, surgeries and malignancies. In central venous occlusion is only necessary to rule out hyperhomocysteinemia and antiphospholipid antibody syndrome in young patients without known risk factors. In central artery occlusion, hypercoagulable workup is only recommended for patients less than 50 years-old with unknown emboli source. In this cases protein C, protein S, and antithrombin III deficiencies, homocystein, sickle cell disease and antiphospholipid antibody syndrome will ruled out. In non arteritic ischemic optic neuropathy hypercoagulable work up is not necessary. In amaurosis fugax without known emboli source, it is recommended to rule out etiologies of arterial occlusion, especially antithrombin III deficiencies, homocystein, sickle cell disease and antiphospholipid antibody syndrome.
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PMID:[Hypercoagulable workup in ophthalmology. When and what]. 1965 50


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