Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The patient first noticed general muscle stiffness at the age of 36. Two years later, she suffered from a tonic-clonic seizure which brought her to a hospital for the first time. Choreoathetoid movement, ataxia and cognitive deficit were apparent. At the age of 44, tonic-clonic seizures became more frequent and she was admitted to our hospital as being status epilepticus. After the cessation of clinical seizures, she became appllic. Gradual increase of atrophic changes in cerebrum, cerebellum and brain stem were observed by MRI and CT. Hematological study showed that she had abnormal hemoglobin, Hb Takamatsu. Four of her five children were clinically examined; all of them showed abnormal EEG findings; three being mentally retarded and had clinical generalized convulsive seizures; two had hemoglobinopathy (Hb Takamatsu). The patient died from sepsis at the age of 50 and the autopsy was carried out. The brain weighed 930 gram. Histological findings confirmed the diagnosis of dentato-rubro-pallido-luysian atrophy; neuronal loss accompanied by gliosis in dentate nuclei, red nuclei, lateral part of globus pallidus, and subthalamic nuclei. The coincidence of the hereditary traits of two independent diseases, DRPLA and familial hemoglobinopathy (Hb Takamatsu) suggests closeness of their genetic loci.
 ...
PMID:[A familial case of DRPLA diagnosed by an autopsy associated with hemoglobinopathy (Hb Takamatsu)]. 825 33

Four children with major sickle hemoglobinopathies developed severe pneumococcal infection. Three had sickle cell hemoglobin C (Hb SC) disease and one had sickle cell anemia (Hb SS). In three instances, there was a fatal outcome. The authors' experience with these cases leads them to question whether any patient with a major sickle hemoglobinopathy should be excluded from receiving prophylactic penicillin or if outpatient management with long-acting cephalosporin treatment in the sickle cell patient with suspected sepsis is appropriate therapy.
 ...
PMID:Infection in major sickle hemoglobinopathies: should management strategies change? 825 43

Twenty-two arthroplasties were performed in 14 patients with sickle cell hemoglobinopathy (SCH). There were 15 primary and seven revision procedures; none were lost to follow-up evaluation. In the primary arthroplasty group, there were two deaths in patients whose implants were functioning well. The remaining 13 hips had a mean follow-up period of 4.8 years. Failure occurred in five of these 13 hips (38%), four due to aseptic acetabular loosening and one due to sepsis. In the revision arthroplasty group, at a mean follow-up period of 5.3 years, failure occurred in three hips (43%), one due to acetabular loosening, one due to femoral loosening, and one due to sepsis. Perioperative complication rates were high in both groups. Femoral intramedullary sclerosis and bone altered by marrow hyperplasia were associated with intraoperative technical difficulties as well as problems with achieving long-term component fixation. Though total hip arthroplasty provides the most reliable measure of effective treatment in SCH, it carries a high risk of complications and failure.
 ...
PMID:Total hip arthroplasty in sickle cell hemoglobinopathy. 835 6

Hemoglobin S/O(Arab) (Hb S/O(Arab)) is a rare compound heterozygous hemoglobinopathy characterized by the presence of two variant beta-globin chains: beta6Glu --> Val (Hb S) and beta121Glu --> Lys (Hb O(Arab)). The diagnosis of Hb S/O(Arab) requires electrophoresis on both cellulose acetate and citrate agar, since Hb O(Arab) co-migrates with Hb C at alkaline pH and close to Hb S at acidic pH. To date only case reports and small series of patients with Hb S/O(Arab) have been described. To better characterize the clinical and laboratory aspects of this unusual disorder, we reviewed the Duke University Medical Center experience. We identified 13 African-American children and adults with Hb S/O(Arab) ranging in age from 2.7 to 62.5 years. All patients had hemolytic anemia with a median Hb of 8.7 gm/dL (range 6.1-9.9 gm/dL), and a median reticulocyte count of 5.8% (range 1.2-10.3%). The peripheral blood smear typically showed sickled erythrocytes, target cells, polychromasia, and nucleated red blood cells. All 13 patients have had significant clinical sickling events including acute chest syndrome (11), recurrent vasoocclusive painful events (10), dactylitis (7), gallstones (5), nephropathy (4), aplastic crises (2), avascular necrosis (2), leg ulcers (2), cerebrovascular accident (CVA) (1), osteomyelitis (1), and retinopathy (1). Four patients have died, including two from pneumococcal sepsis/meningitis at ages 5 and 10 years, one of acute chest syndrome at age 14 years, and one of multiorgan failure at age 35 years. We conclude that Hb S/O(Arab) disease is a severe sickling hemoglobinopathy with laboratory and clinical manifestations similar to those of homozygous sickle cell anemia.
 ...
PMID:Hemoglobin S/O(Arab): thirteen new cases and review of the literature. 1020 1

In Oklahoma since the early 1990s, all newborns have been screened for four metabolic conditions: phenylketonuria, hypothyroidism, galactosemia and hemoglobinopathies. In 2002, 38 affected babies were diagnosed and one expects they are saved from the complications of late diagnosis such as mental retardation or death from sepsis. With advances in genetics and improved biochemical assays, 86% of states now screen for more disorders than Oklahoma, up to 37 in Mississippi. Six recent patient vignettes illustrate the mortality and morbidity of conditions that are screened for elsewhere but not in Oklahoma. In 2001, the Oklahoma Genetics Advisory Council recommended adding three disorders and the State Health Department forecasts that implementation may be complete in 2007. For now, when a patient asks, "Will my baby be screened for as many metabolic conditions as possible?", two answers represent either the public health or the private health care view. The public health answer is, "The state requires screening for four conditions." The health care system answer is, "We can work with you to get 44 conditions tested for, but it will cost money, may not be reimbursed, and has not been proven effective when done on an individual basis." This dilemma, not unique to newborn screening, might be resolved if professional and public opinion strongly supported early expansion.
 ...
PMID:Expanding metabolic screening of newborns: can the health care industry do better than public health? 1461 2

Thalassemia is the commonest hemoglobinopathy in Malaysia. Patients with thalassemia major are transfusion dependent, and a large proportion of them will require splenectomy. As this particular group of patients is immunocompromized, overwhelming sepsis is a recognized complication. We report a series of three patients who all developed intra-abdominal abscesses following splenectomy.
 ...
PMID:Case report post-splenectomy sepsis in thalassemic patients. 1591 58

Bacterial infections are considered a major cause of morbidity and mortality in patients, particularly children, with sickle cell disease. Infections including pneumonia, meningitis, osteomyelitis, pyelonephritis and general sepsis are more prevalent in patients with these genetic abnormalities than in normal individuals. Generally, infections are more prevalent in children than in older patients. The most common cause of severe infections in hemoglobinopathies include Diplococcus, Staphylococcus, Pneumococcus, Salmonella and Streptococcus. Several investigations have been conducted to determine the possible defects in the host defense mechanisms. Functional asplenia, defects in alternate pathway and in opsonic activity and phagocytosis of Streptococci, Staphylococci and Salmonella in sickle cell anemia patients are considered important factors predisposing these patients to bacteremia. On the other hand, a beneficial association has been demonstrated between the sickle cell gene and malaria. The hemoglobin S (Hb S) provides a natural resistance against the malarial parasite resulting in an improvement in fitness and survival over the normal (Hb AA) individuals. This communication reviews infections in sickle cell disease with a comparison of results in various populations.
 ...
PMID:Infections in sickle cell disease. 2116 37

Routine clinical and laboratory assessments facilitate diagnosis of erythropoietin (EPO) resistant anemia by allowing early identification of patients with non-adherence. Any new event that impairs response to EPO (e.g., catheter sepsis) must be promptly controlled. Because of the confounding interaction of its risk factors, initial evaluation should include nutrition, dialysis adequacy, hemorrhage, bone mineral metabolism, and inflammation. Prevention of EPO resistance is more cost effective and should include adequate dialysis and nutritional supplements. Blood loss during hemodialysis (HD) procedures should be minimized. If there is laboratory proof of iron deficit intravenous repletion is most effective. Oxidative stress may be attenuated by vitamins E and C, while optimal control of hyperparathyroidism will enhance EPO stimulation. Contaminated dialysates should be suspected if there is EPO-stimulating agents (ESA) resistance at the same time among most members of a dialysis program. Heavy metal toxicity should be suspected in high-risk patients. The impact of co-morbidities such as hemoglobinopathy, glucose 6 phosphate dehydrogenase (G6PD) deficiency and connective tissue diseases must be excluded in an appropriate setting. In conclusion, given the multiple risk factors of EPO resistance promotion of the overall health status will most likely yield an enduring benefit. Finally, there are experimental trials of gene-based (therapy) to stimulate endogenous EPO synthesis with the goal of avoiding the off-target effect of excessive dosing.
 ...
PMID:Resistance to erythropoietin-stimulating agents: etiology, evaluation, and therapeutic considerations. 2142 25

Intravascular hemolysis produces injury in a variety of human diseases including hemoglobinopathies, malaria, and sepsis. The adverse effects of increased plasma hemoglobin are partly mediated by depletion of nitric oxide (NO) and result in vasoconstriction. Circulating plasma proteins haptoglobin and hemopexin scavenge extracellular hemoglobin and cell-free heme, respectively. The ability of human haptoglobin or hemopexin to inhibit the adverse effects of NO scavenging by circulating murine hemoglobin was tested in C57Bl/6 mice. In healthy awake mice, the systemic hemodynamic effects of intravenous coinfusion of cell-free hemoglobin and exogenous haptoglobin or of cell-free hemoglobin and hemopexin were compared with the hemodynamic effects of infusion of cell-free hemoglobin or control protein (albumin) alone. We also studied the hemodynamic effects of infusing hemoglobin and haptoglobin as well as injecting either hemoglobin or albumin alone in mice fed a high-fat diet (HFD) and in diabetic (db/db) mice. Coinfusion of a 1:1 weight ratio of haptoglobin but not hemopexin with cell-free hemoglobin prevented hemoglobin-induced systemic hypertension in healthy awake mice. In mice fed a HFD and in diabetic mice, coinfusion of haptoglobin mixed with an equal mass of cell-free hemoglobin did not reverse hemoglobin-induced hypertension. Haptoglobin retained cell-free hemoglobin in plasma, but neither haptoglobin nor hemopexin affected the ability of hemoglobin to scavenge NO ex vivo. In conclusion, in healthy C57Bl/6 mice with normal endothelium, coadministration of haptoglobin but not hemopexin with cell-free hemoglobin prevents acute hemoglobin-induced systemic hypertension by compartmentalizing cell-free hemoglobin in plasma. In murine diseases associated with endothelial dysfunction, haptoglobin therapy appears to be insufficient to prevent hemoglobin-induced vasoconstriction.NEW & NOTEWORTHY Coadministraton of haptoglobin but not hemopexin with cell-free hemoglobin prevents hemoglobin-induced systemic hypertension in mice with a normal endothelium. In contrast, treatment with the same amount of haptoglobin is unable to prevent hemoglobin-induced vasoconstriction in mice with hyperlipidemia or diabetes mellitus, disorders that are associated with endothelial dysfunction.
 ...
PMID:Endothelial dysfunction inhibits the ability of haptoglobin to prevent hemoglobin-induced hypertension. 2831 63

State-of-the-art proteomics technologies have recently helped to elucidate the unanticipated complexity of red blood cell metabolism. One recent example is citrate metabolism, which is catalyzed by cytosolic isoforms of Krebs cycle enzymes that are present and active in mature erythrocytes and was determined using quantitative metabolic flux analysis. In previous studies, we reported significant increases in glycolytic fluxes in red blood cells exposed to hypoxia in vitro or in vivo, an observation relevant to transfusion medicine owing to the potential benefits associated with hypoxic storage of packed red blood cells. Here, using a combination of steady state and quantitative tracing metabolomics experiments with 13C1,2,3-glucose, 13C6-citrate, 13C515N2-glutamine, and 13C1-aspartate via ultra-high performance liquid chromatography coupled on line with mass spectrometry, we observed that hypoxia in vivo and in vitro promotes consumption of citrate and other carboxylates. These metabolic reactions are theoretically explained by the activity of cytosolic malate dehydrogenase 1 and isocitrate dehydrogenase 1 (abundantly represented in the red blood cell proteome), though moonlighting functions of additional enzymes cannot be ruled out. These observations enhance understanding of red blood cell metabolic responses to hypoxia, which could be relevant to understand systemic physiological and pathological responses to high altitude, ischemia, hemorrhage, sepsis, pulmonary hypertension, or hemoglobinopathies. Results from this study will also inform the design and testing of novel additive solutions that optimize red blood cell storage under oxygen-controlled conditions.
 ...
PMID:Metabolism of Citrate and Other Carboxylic Acids in Erythrocytes As a Function of Oxygen Saturation and Refrigerated Storage. 2909 Feb 12


<< Previous 1 2 3 Next >>