Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiology, symptomatology, and treatment of Wilson's disease are reviewed, and new approaches to drug management are discussed. Wilson's disease is a rare, autosomal recessive disorder that occurs between the ages of 6 and 60 years. Disturbances in copper metabolism may result in the accumulation of excess copper in the liver, the basal ganglia of the brain (lenticular degeneration), the kidneys, the cornea (Kayser-Fleischer rings), and other tissues. The diagnosis of Wilson's disease is frequently overlooked; nonspecific symptoms and multisystem involvement may mimic other disease states, such as neurologic and psychiatric disorders, and hemolytic anemia. Screening tests for Wilson's disease include 24-hour urinary copper levels, serum ceruloplasmin and copper assays, radioactive uptake of 64Cu, and liver biopsy. Current methods of therapy include the use of a chelating agent--penicillamine or trientine--for initial rapid decoppering. Penicillamine therapy has been associated with many adverse reactions, including worsening of the neurologic symptoms of the patient. Zinc is a useful agent for maintenance therapy. Investigational studies exploring the use of ammonium tetrathiomolybdate for initial rapid decoppering have shown promising results. Unless it is recognized and treated, Wilson's disease can cause severe symptoms and, ultimately, death. Initial rapid decoppering with chelating agents, such as penicillamine and trientine, followed by lifelong maintenance therapy with zinc is the current method of treatment.
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PMID:Pathophysiology and treatment of Wilson's disease. 179 20

Congenital erythropoietic porphyria (CEP) is a rare disorder of heme biosynthesis that results in the production of large quantities of photoactive porphyrins. The clinical syndrome is dominated by extreme photosensitivity with mutilation of light exposed extremities and hemolytic anemia. Bone disease has been occasionally noted, but is not well characterised. We describe a man with CEP who developed bone pain and spinal crush fractures at the age of 22. Skeletal radiographs revealed features typical of other severe hemolytic anemias, but in addition there was loss of the terminal phalanges of the hand as a result of photomutilation. Spinal bone density (assessed by DPA) was reduced and at the hip bone density was at the lower limit of normal. The metacarpal cortical bone density was 2.9 standard deviations below normal. Biochemical and histological studies accelerated bone turnover. Although the serum 250H vitamin D concentration was very low (because of light avoidance) there was no evidence that the bone disease was a consequence of this. Treatment for one year with clodronate and a high transfusion regime was associated with small reductions in serum alkaline phosphatase and urine hydroxyproline excretion, but there was no improvement in bone mineral density. We conclude that CEP has a distinctive osteodystrophy comprising osteolysis of light-exposed extremities and a high turnover type of osteoporosis. Privational vitamin D deficiency may also occur. The effect upon bone of the new therapies for CEP should be considered.
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PMID:The osteodystrophy of congenital erythropoietic porphyria. 206 45

The clinical analytical and therapeutic results of a retrospective study of 11 cases of Wilson's disease carried out in "La Fe" Hospital in Valencia are presented. The disease had a neurological onset in 5 cases, an hepatic onset in 4 cases (3 acute hepatitis and 1 chronic hypertransaminemia), 2 cases started as an acute hemolytic anemia; one of the outbreaks occurred during a period of treatment interruption. Diagnosis showed some difficulty in one case since the disease was associated with positive hepatitis B markers, positive anti HIV antibodies and initially normal ceruloplasminemia values. The diagnostic difficulties derived from the interpretation of ceruloplasminemia, and blood and urine copper levels are pointed out as well as the difficulties encountered in our environment to determine intrahepatic copper levels and to perform a kinetic study with radioactive copper both of which are of vital importance to confirm doubtful cases. Two patients became pregnant in the course of the disease having normal pregnancies and deliveries, without any apparent abnormalities in the newborns. Treatment with D-Penicillamine was started in 9 cases, observing a low to moderate intolerance in 7 cases; there was one case of severe intolerance for which treatment had to be interrupted. The new therapeutical approaches based on the use of trientine (not available in our country) are discussed, together with the expectations of liver transplant in this disease.
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PMID:[Wilson's disease: difficulties in diagnosis and therapeutic management in our country]. 262 49

Wilson's disease (WD), an inborn error of copper (Cu) metabolism, is now one of the leading liver diseases in children in India. The clinical presentation can be extremely varied viz.,--all forms of acute and chronic liver disease, minimal to severe neurological disease, psychiatric problems, bony deformities, hemolytic anemia and endocrine manifestations. A high index of suspicion is necessary along with a judicious battery of investigations for diagnosis. Hepatic copper estimation is the most reliable test but is not easily available in India. Liver biopsy may not be possible because of bleeding problems and histological features are often not diagnostic of WD. In the absence of hepatic Cu, a low ceruloplasmin, high 24 hour urinary copper and presence of KF rings aid in making the diagnosis. The mainstay of initial therapy is Cu-chelators like D-Penicillamine, and Trientine for reduction in body copper to sub-toxic levels. Subsequent maintenance therapy is necessarily lifelong with D-Penicillamine, Trientine or Zinc. Children on therapy must be monitored regularly for response, side-effects, compliance and rehabilitation. Response to therapy may be unpredictable, but acute and early presentations like fulminant hepatic failures have a poor outcome. All siblings must be screened for WD as early diagnosis and treatment result in a good outcome. The identification of the WD gene on chromosome 13 has led to the possible use of molecular genetics (haplotype and mutational analyses) in the diagnosis of WD. Parent groups/associations must take active part in holistic management of WD.
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PMID:Wilson's disease. 1242 Sep 12

A 17-year-old girl with haemolytic anaemia, parenchymal livel disease and gallbladder calculi, is reported. Kayser-Fleischer rings, transaminasaemia, deficiency of ceruloplasmin, increased cupriuria, and nodular cirrhosis of the liver, confirmed the diagnosis of Wilson's disease. Penicillamine therapy had to be interrupted a short time after it was started, because of penicillamine-induces acute psychotic episode. Zinc-sulphate has controlled Wilson's disease in the patient.
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PMID:[Wilson's disease]. 1797 25

Wilson disease is a rare, inherited autosomal recessive disease of copper metabolism and may be more common where consanguinity is prevalent. Much has been known about the disease after it was first described by Kinnier Wilson as 'progressive lenticular degeneration in 1912. Over 500 mutations of the ATP7B gene has been identified with no clear genotype to phenotype correlation. Loss of ATP7B function leads various grades of reduced biliary excretion of copper and reduced incorporation of copper into ceruloplasmin; accumulation and toxicity of copper in the liver, brain and other tissues results in liver toxicity and other myriad manifestations of the disease. The clinical features may vary from asymptomatic state to chronic liver disease, acute liver failure, neuropsychiatric manifestations and hemolytic anemia. Diagnosis is based on the combination of clinical sign's, biochemical features, histologic findings and mutation analysis of ATP7B gene. Subtle geographical differences exist with a disproportionate proportion of children presenting with acute liver failure. A high index of suspicion is needed for an early diagnosis. Ratios of biochemical indices for early diagnosis need validation across geographical regions and may not be particularly applicable in children. Better biomarkers or the need for tests for early detection of ALF persists. Drugs used in the treatment of Wilson disease include copper chelating agents such as d-Penicillamine, trientine and zinc salt. Untreated Wilson disease uniformly leads to death from liver disease or severe neurological disability. Early recognition and treatment has excellent prognosis. Liver transplantation is indicated in acute liver failure and end stage liver disease. Family screening in order to detect the disorder in the first-degree relatives is warranted. This review provides an overview of different aspects of Wilson disease including geographical differences in presentations and clinical management and the limitations of currently available tests.
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PMID:A review and current perspective on Wilson disease. 2575 20