Intractable & Rare Diseases Research
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Volume 3 , Issue 2
Showing 1-5 articles out of 5 articles from the selected issue
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Review
  • Bernard S. Kaplan, Rebecca L. Ruebner, Joann M. Spinale, Lawrence Cope ...
    Volume 3 (2014) Issue 2 Pages 34-45
    Released: June 06, 2014
    JOURNALS FREE ACCESS
    Tremendous advances have been made in understanding the pathogenesis of atypical Hemolytic Uremic Syndrome (aHUS), an extremely rare disease. Insights into the molecular biology of aHUS resulted in rapid advances in treatment with eculizumab (Soliris®, Alexion Pharmaceuticals Inc.). Historically, aHUS was associated with very high rates of mortality and morbidity. Prior therapies included plasma therapy and/or liver transplantation. Although often life saving, these were imperfect and had many complications. We review the conditions included under the rubric of aHUS: S. pneumoniae HUS (SpHUS), inborn errors of metabolism, and disorders of complement regulation, emphasizing their differences and similarities. We focus on the clinical features, diagnosis, and pathogenesis, and treatment of aHUS that results from mutations in genes encoding alternative complement regulators, SpHUS and HUS associated with inborn errors of metabolism. Mutations in complement genes, or antibodies to their protein products, result in unregulated activity of the alternate complement pathway, endothelial injury, and thrombotic microangiopathy (TMA). Eculizumab is a humanized monoclonal antibody that inhibits the production of the terminal complement components C5a and the membrane attack complex (C5b-9) by binding to complement protein C5a. This blocks the proinflammatory and cytolytic effects of terminal complement activation. Eculizumab use has been reported in many case reports, and retrospective and prospective clinical trials in aHUS. There have been few serious side effects and no reports of tachphylaxis or drug resistance. The results are very encouraging and eculizumab is now recognized as the treatment of choice for aHUS.
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Original Article
  • Kenichi Mishima, Hiroshi Kitoh, Nobuhiko Haga, Yasuharu Nakashima, Jun ...
    Volume 3 (2014) Issue 2 Pages 46-51
    Released: June 06, 2014
    JOURNALS FREE ACCESS
    Fibrodysplasia ossificans progressiva (FOP) is a disabling heritable disorder of connective tissue characterized by progressive heterotopic ossification in various extraskeletal sites. Early correct diagnosis of FOP is important to prevent additional iatrogenic harm or trauma. Congenital malformation of the great toes is a well-known diagnostic clue, but some patients show normal-appearing great toes. The thumb shortening and cervical spine abnormalities are other skeletal features often observed in FOP. This study aimed to address the quantitative assessment of these features in a cohort of patients with FOP, which potentially helps early diagnosis of FOP. Radiographs of the hand and cervical spine were retrospectively analyzed from a total of 18 FOP patients (9 males and 9 females) with an average age of 13.9 years (range 0.7-39.3 years). The elevated ratio of the second metacarpal bone to the distal phalanx of the thumb (> +1SD) was a consistent finding irrespective of the patient's age and gender. Infant FOP patients, in addition, exhibited an extremely high ratio of the second metacarpal bone to the first metacarpal bone (> +3SD). The height/depth ratio of the C5 vertebra increased in patients over 4 years of age (> +2SD). Additionally, the ratio of (height+depth) of the C5 spinous process to the C5 vertebral depth was markedly elevated in young patients (> +2SD). We quantitatively demonstrated the hand and cervical spine characteristics of FOP. These findings, which can be seen from early infancy, could be useful for early diagnosis of FOP even in patients without great toe abnormalities.
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Case Reports
  • Yisha Tong
    Volume 3 (2014) Issue 2 Pages 52-56
    Released: June 06, 2014
    JOURNALS FREE ACCESS
    Pyridoxine (vitamin B6) deficiency is a recognised cause of intractable seizures in neonates. However, pyridoxine deficiency related seizures in adults were rarely reported. This article reports a case of a 79 year old lady who suffered from new-onset seizures and was successfully treated with vitamin B6. The patient had chronic renal disease and weight loss due to anepithymia following a pelvic fracture. This article also reviews literatures of seizures caused by pyridoxine deficiency in adults. Seizures caused by vitamin B6 deficiency in adults may result from dietary deficiency, liver disease, pregnancy and certain medications and can be easily treated by vitamin B6 with excellent outcome. Clinicians should consider vitamin B6 deficiency as a potential aetiology of seizures, even in patients who suffer from other underlying diseases which can cause seizures.
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  • Liqiong Liu, Jonathan Stone, Joan T. Hoffpauir, Zhenggang Xiong
    Volume 3 (2014) Issue 2 Pages 57-59
    Released: June 06, 2014
    JOURNALS FREE ACCESS
    Meningioma with extensive histiocytic changes is rare. We describe a case of histiocytic meningioma which occurred in a 55-year-old woman. The patient had a progressive headache and a decline in fine motor coordination and memory for the past four years. Magnetic resonance imaging demonstrated a well-demarcated, dura-based and contrast-enhancing mass lesion in the right superior frontoparietal region. Histopathologically, the tumor showed neoplastic meningothelial proliferation with extensive and multifocal histiocytic infiltration. The histiocytic component constituted approximately half of the entire tumor. Immunohistochemically, both meningothelial and histiocytic cells showed immunoreactivity for epithelial membrane antigen (EMA), while the histiocytic cells were also positive for CD4 and CD68. In addition, there were scattered S100-positive histiocytes throughout the tumor. Proliferative index highlighted by Ki67 immunostain was 1.6%. There were no high-grade changes such as frequent mitoses, necrosis, or brain parenchymal invasion in the specimen. With review of the literature, we propose that this type of meningioma should be considered as a separate subtype of meningioma. The biological basis and differential diagnosis are discussed.
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Commentary
  • Claire L. Shovlin
    Volume 3 (2014) Issue 2 Pages 60-64
    Released: June 06, 2014
    JOURNALS FREE ACCESS
    Has the recent identification of iron deficiency as a risk factor for ischaemic stroke in patients with pulmonary arteriovenous malformations (AVMs) unmasked a new paradigm for stroke/infarct pathogenesis? This commentary reviews evidence that spans associations between iron deficiency and ischaemic strokes, iron deficiency enhancement of platelet aggregation in response to serotonin/5HT, settings in which plasma 5HT is elevated, and clinical trial confirmation that 5HT receptor antagonists prevent ischaemic stroke. The critical leap which directs attention away from atherothrombotic events at the neurovascular wall is that ischaemic strokes due to pulmonary AVMs are attributable to compromised pulmonary capillary bed filtration of venous blood. Right-to-left shunting is continuous through pulmonary AVMs, but also occurs intermittently in approximately 30% of the general population with intracardiac shunts such as patent foramen ovale (PFO). The testable hypothesis presented is that paradoxical embolism of venous platelet-based aggregates may constitute part of the causal chain between iron deficiency and ischaemic stroke, not only in the rare disease state of pulmonary AVMs, but also in major subgroups of the general population.
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