Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aberrant smooth muscle dystonia during hemolytic episodes in paroxysmal nocturnal hemoglobinuria (PNH) is implicated in the symptoms of abdominal pain, dysphagia and erectile dysfunction. Here we report two PNH patients treated with the complement inhibitor, eculizumab. Complement inhibition has been sustained for over 2 years and results in resolution of intravascular hemolysis and amelioration of symptoms associated with smooth muscle contractions.
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PMID:Improvement in the symptoms of smooth muscle dystonia during eculizumab therapy in paroxysmal nocturnal hemoglobinuria. 1646 55

A 69-year-old man with advanced heart failure treated with a continuous-flow left ventricular assist device presented for evaluation of dark urine and severe dysphagia. Because of evidence of ongoing intravascular hemolysis with device dysfunction, there was a clinical suspicion for pump thrombosis. He had progressive end-organ dysfunction and was therefore treated with tissue plasminogen activator with prompt resolution in hemolysis and dysphagia. Although symptoms of smooth muscle dystonia could represent worsening heart failure in the setting of device failure, the observation may also be related to intravascular hemolysis as described in the prototypic hemolytic disease, paroxysmal nocturnal hemoglobinuria.
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PMID:Dysphagia in the setting of left ventricular assist device hemolysis. 2364 23

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder of the hematopoietic stem cell that makes blood cells more sensitive to the action of complement. Patients experience intravascular hemolysis, smooth muscle dystonia, renal failure, arterial and pulmonary hypertension, recurrent infectious diseases and an increased risk of notably dreadful thrombotic complications. The diagnosis is made by flow cytometry. Efforts have been recently performed to improve the sensitivity and the standardization of this technique. PNH is frequently associated with aplastic anemia or low-risk myelodysplasia and may be asymptomatic. Management of the classical form of PNH has been dramatically revolutionized by the development of eculizumab, which brings benefits in terms of hemolysis, quality of life, renal function, thrombotic risk, and life expectancy. Prophylaxis and treatment of arterial and venous thrombosis currently remain a challenge in PNH.
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PMID:Pathophysiology, diagnosis, and treatment of paroxysmal nocturnal hemoglobinuria: a review. 2575

Paroxysmal nocturnal hemoglobinurea (PNH) is a rare disorder of complement regulation due to somatic mutation of PIGA (phosphatidylinositol glycan anchor) gene. We herewith report a case who developed a symptomatic PNH long after an allogenic marrow transplant. Some reasonable arguments concerning the origin of PNH clone have been discussed. The molecular studies revealed presence of JAK2 and TET2 mutations without a BCOR mutation. The literature review has been performed to probe into the complex interplay of autoimmunity and clonal selection and expansion of PNH cells, which occurs early in hematopoietic differentiation. The consequent events such as hypoplastic and/or hemato-oncologic features could further be explained on the basis of next-generation sequencing (NGS) studies. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder of hematopoietic stem cells, characterized by a somatic mutation of the phosphatidylinositol glycan-class A (PIGA). The PIGA gene products are crucial for biosynthesis of glycosylphosphatidylinositol (GPI) anchors, which attaches a number of proteins to the plasma membrane of the cell. Amongst these proteins, the CD55 and CD59 are complement regulatory proteins. The CD55 inhibits C3 convertase whereas the CD59 blocks the membrane attack complex (MAC) by inhibiting the incorporation of C9 to MAC. The loss of complement regulatory protein renders the red cell susceptible to complement-mediated lysis leading to intravascular and extravascular hemolysis. The intravascular hemolysis explains most of the morbid clinical manifestations of the disease. The clinical features of syndrome of PNH are recurrent hemolytic episodes, thrombosis, smooth muscle dystonia, and bone marrow failure; other important complications include renal failure, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). The most used therapies were blood transfusions, immunosuppressive, and steroid. Allogeneic stem cell transplantation was also practiced. At present, the therapy of choice is eculizumab (Soliris, Alexion Pharmaceuticals), a humanized monoclonal antibody that blocks activation of the terminal complement at C5. The limiting factor for this therapy is breakthrough hemolysis and the frequent dosing schedule. Ravulizumab (ALXN1210) is the second generation terminal compliment inhibitor which seems to provide a sustained control of hemolysis without breakthrough hemolysis and with a longer dosing interval.
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PMID:Paroxysmal Nocturnal Hemoglobinuria with a Distinct Molecular Signature Diagnosed Ten Years after Allogenic Bone Marrow Transplantation for Acute Myeloid Leukemia. 3086 71