Pulmonary Manifestation of a Primarily Mucocutaneous Hereditary Disease

2020 ◽  
Vol 56 (7) ◽  
pp. 468-469
Author(s):  
Virginia Guevara Velázquez ◽  
José María González Ruiz ◽  
Elena García Arias-Salgado ◽  
Rosa Cordovilla Pérez ◽  
Miguel Iglesias Heras ◽  
...  
2011 ◽  
Vol 50 (06) ◽  
pp. N64-N65 ◽  
Author(s):  
B. Bodmann ◽  
V. Havranek ◽  
M. Kneussl ◽  
J. Czernin ◽  
P. Knoll ◽  
...  

2016 ◽  
Vol 55 (01) ◽  
pp. 34-40 ◽  
Author(s):  
P. Zschieschang ◽  
V. Prasad ◽  
D. Moskopp ◽  
B. Knie ◽  
M. Plotkin

SummaryAim: Hereditary pheochromocytoma-paraganglioma syndromes are characterized by multiple pheochromocytomas (PCC) and paragangliomas (PGLs), inherited in an autosomal dominant manner. Early detection and removal of tumours may prevent or minimize complications related to mass effects and malignant transformation. Having confirmed the diagnosis, it is important to localize the tumours and reveal their extent preoperatively. This study aimed to introduce 18F-DOPA PET/CT as a highly sensitive noninvasive diagnostic tool for early detection of mass lesions in patients with pheochromocytoma-paraganglioma inherited tumour syndrome and to report about its impact on patient management. Patients, methods: We are currently supervising one of the largest documented families in Germany with genetically determined SDHD gene mutation. We performed 18F-DOPA PET/CT in order to detect tumours in asymptomatic gene carriers and enable subsequent surgical therapy. Results: In seven patients undergoing 12 18F-DOPA PET/CT scans 17 lesions have been detected. Three of these lesions, located in the head and neck region, have had no morphologic correlate in CT and one had also no morphologic correlate in MRI. Of the six histologically analyzed lesions five have been tumors (PGL or PCC) and one has been a nodular hyperplasia. This means the 18F-DOPA PET/CT scan in our study group had a sensitivity of 83%. 18F-DOPA PET/CT investigations lead to change in the management in 5/7 studied patients (70%). Conclusion: The benefits of PET/ CT in detection of pheochromocytoma and paraganglioma are well documented, but we are the first to use this technique for screening of a rare hereditary disease (estimated prevalence 0.3/100 000).


Author(s):  
Chandan Kumar ◽  
Sandeep Aggarwal ◽  
Abhishek Abhishek ◽  
Pal Satyajit Singh Athwal ◽  
Anil Kumar Kem

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aubin Michalon ◽  
Andreas Hagenbuch ◽  
Christian Huy ◽  
Evita Varela ◽  
Benoit Combaluzier ◽  
...  

AbstractTransthyretin amyloid (ATTR) cardiomyopathy is a debilitating disease leading to heart failure and death. It is characterized by the deposition of extracellular ATTR fibrils in the myocardium. Reducing myocardial ATTR load is a therapeutic goal anticipated to translate into restored cardiac function and improved patient survival. For this purpose, we developed the selective anti-ATTR antibody NI301A, a recombinant human monoclonal immunoglobulin G1. NI301A was cloned following comprehensive analyses of memory B cell repertoires derived from healthy elderly subjects. NI301A binds selectively with high affinity to the disease-associated ATTR aggregates of either wild-type or variant ATTR related to sporadic or hereditary disease, respectively. It does not bind physiological transthyretin. NI301A removes ATTR deposits ex vivo from patient-derived myocardium by macrophages, as well as in vivo from mice grafted with patient-derived ATTR fibrils in a dose- and time-dependent fashion. The biological activity of ATTR removal involves antibody-mediated activation of phagocytic immune cells including macrophages. These data support the evaluation of safety and tolerability of NI301A in an ongoing phase 1 clinical trial in patients with ATTR cardiomyopathy.


2009 ◽  
Vol 422 (1) ◽  
pp. 161-170 ◽  
Author(s):  
Ana Ibáñez ◽  
Paula Río ◽  
José Antonio Casado ◽  
Juan Antonio Bueren ◽  
José Luis Fernández-Luna ◽  
...  

FA (Fanconi anaemia) is a hereditary disease characterized by congenital malformations, progressive bone marrow failure and an extraordinary elevated predisposition to develop cancer. In the present manuscript we describe an anomalous high level of the proinflammatory cytokine IL-1β (interleukin-1β) present in the serum of FA patients. The elevated levels of IL-1β were completely reverted by transduction of a wild-type copy of the FancA cDNA into FA-A (FA group A) lymphocytes. Although the transcription factor NF-κB (nuclear factor-κB) is a well established regulator of IL-1β expression, our experiments did not show any proof of elevated NF-κB activity in FA-A cells. However, we found that the overexpression of IL-1β in FA-A cells is related to a constitutively activated PI3K (phosphoinositide 3-kinase)-Akt pathway in these cells. We provide evidence that the effect of Akt on IL-1β activation is mediated by the inhibition of GSK3β (glycogen synthase kinase 3β). Finally, our data indicate that the levels of IL-1β produced by FA-A lymphoblasts are enough to promote an activation of the cell cycle in primary glioblastoma progenitor cells. Together, these results demonstrate that the constitutive activation of the PI3K-Akt pathway in FA cells upregulates the expression of IL-1β through an NF-κB-independent mechanism and that this overproduction activates the proliferation of tumour cells.


2021 ◽  
Vol 22 (8) ◽  
pp. 4009
Author(s):  
Maik Liedtke ◽  
Christin Völkner ◽  
Alexandra V. Jürs ◽  
Franziska Peter ◽  
Michael Rabenstein ◽  
...  

Niemann-Pick type C2 (NP-C2) disease is a rare hereditary disease caused by mutations in the NPC2 gene. NPC2 is a small, soluble protein consisting of 151 amino acids, primarily expressed in late endosomes and lysosomes (LE/LY). Together with NPC1, a transmembrane protein found in these organelles, NPC2 accomplishes the exclusion of cholesterol; thus, both proteins are essential to maintain cellular cholesterol homeostasis. Consequently, mutations in the NPC2 or NPC1 gene result in pathophysiological accumulation of cholesterol and sphingolipids in LE/LY. The vast majority of Niemann-Pick type C disease patients, 95%, suffer from a mutation of NPC1, and only 5% display a mutation of NPC2. The biochemical phenotype of NP-C1 and NP-C2 appears to be indistinguishable, and both diseases share several commonalities in the clinical manifestation. Studies of the pathological mechanisms underlying NP-C2 are mostly based on NP-C2 animal models and NP-C2 patient-derived fibroblasts. Recently, we established induced pluripotent stem cells (iPSCs), derived from a donor carrying the NPC2 mutations c.58G>T/c.140G>T. Here, we present a profile of pathophysiological in vitro features, shared by NP-C1 and NP-C2, of neural differentiated cells obtained from the patient specific iPSCs. Profiling comprised a determination of the NPC2 protein level, detection of cholesterol accumulation by filipin staining, analysis of oxidative stress, and determination of autophagy. As expected, the NPC2-deficient cells displayed a significantly reduced amount of NPC2 protein, and, accordingly, we observed a significantly increased amount of cholesterol. Most notably, NPC2-deficient cells displayed only a slight increase of reactive oxygen species (ROS), suggesting that they do not suffer from oxidative stress and express catalase at a high level. As a site note, comparable NPC1-deficient cells suffer from a lack of catalase and display an increased level of ROS. In summary, this cell line provides a valuable tool to gain deeper understanding, not only of the pathogenic mechanism of NP-C2, but also of NP-C1.


2020 ◽  
Vol 33 (6) ◽  
pp. 793-802 ◽  
Author(s):  
Weijing Kong ◽  
Yan Meng ◽  
Liping Zou ◽  
Guang Yang ◽  
Jing Wang ◽  
...  

AbstractObjectivesSanfilippo syndrome (Mucopolysaccharidosis III, MPS III) is a rare autosomal recessive hereditary disease, which is caused by lysosomal enzyme deficiency. This study was operated to investigate clinical and molecular characteristics of patients with MPS III, which will improve the diagnosis and treatment of MPS III.MethodThirty four patients with MPS III were assessed using clinical evaluation, questionnaire, and scoring system.ResultsAmong the 34 patients, 14 had MPS IIIA, 19 had MPS III B, and one had MPS III C. Speech delay (100%) and intellectual disability (100%) were the most prevalent clinical manifestations in this cohort, followed by hyperactivity (94.12%), hirsutism (91.18%), enlarged head circumference (73.52%), repeated diarrhea (67.64%), sparse teeth (67.64%), and Mongolian spots (64.71%). There were two clinical manifestations that were significantly different between IIIA and IIIB: Hepatosplenomegaly and serrated teeth. The most common initial symptoms at diagnosis were speech delay (52.94%), hyperactivity (35.29%), and mental retardation (29.41%). Genetic analysis of 25 patients was conducted, which identified 12 novel mutations.ConclusionWhen language retardation, mental retardation, and rough facial features occurred, MPS III should be considered. At same time, more examination should be operated, such as examination of changes in cranial magnetic resonance imaging of cerebral cortex atrophy. Hepatosplenomegaly and serrated teeth could be used clinically to preliminarily distinguish IIIA from IIIB.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ya-Bing Wang ◽  
Ou Wang ◽  
Min Nie ◽  
Yan Jiang ◽  
Mei Li ◽  
...  

Abstract Background Autoimmune polyendocrine syndrome type 1 (APS1) is a hereditary disease caused by mutations in the AIRE gene with both endocrine and non-endocrine organ involvement. The existing data from China are limited, and this study aims to describe the phenotypes and genetic characterization in Chinese APS1 patients. In this single-center, retrospective, observational study, comprehensive endocrine and extra-endocrine manifestations were collected, and genetic analysis in AIRE was conducted in patients with APS1 between the years of 1984 and 2018 at Peking Union Medical College Hospital. Results In total, 13 patients from 12 unrelated families were enrolled, seven of whom were female, with hypoparathyroidism, chronic mucocutaneous candidiasis, and Addison’s disease being the most frequently observed manifestations. Up to 84.7% presented with two or three of the above-mentioned manifestations, and nearly 4.9 ± 1.8 components presented in patients aged 21.2 ± 7.9 years old. Several less common phenotypes, such as myeloproliferative disease, pure red cell aplasia, renal tubular acidosis, asplenia, autoimmune hepatitis, and ankylosing spondylitis, were also observed in patients. Altogether, seven different AIRE mutations were found in six patients, four of which (K161fs, G208V, A246fs, and L308F) had not been previously reported in patients with APS1. Conclusion We have provided a comprehensive profile of Chinese patients with APS1, with less commonly observed features being observed in addition to more regularly seen manifestations. Additionally, different AIRE mutations that were observed have expanded the genetic spectrum, which will help with future understanding of the molecular pathogenesis of APS1.


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