scholarly journals Triple A Multisystem Disorder: Allgrove Syndrome

Cureus ◽  
2021 ◽  
Author(s):  
Mohamad Alhassoun ◽  
Abdul Hakim Almakadma ◽  
Sami Almustanyir ◽  
Abed AlLehibi ◽  
Nawaf Alotaibi
Keyword(s):  
Multisystem Disorder ◽  
Allgrove Syndrome

Autoimmune Pancreatitis – Diagnosis, Management and Longterm Follow-up

2014 ◽  
Vol 23 (2) ◽  
pp. 179-185 ◽  
Author(s):  
Suvadip Chatterjee ◽  
Kofi W. Oppong ◽  
John S. Scott ◽  
Dave E. Jones ◽  
Richard M. Charnley ◽  
...  
Keyword(s):  
Autoimmune Pancreatitis ◽  
Rare Condition ◽  
Team Approach ◽  
Diagnostic Challenge ◽  
Multisystem Disorder ◽  
North East ◽  
The North ◽  
Work Up ◽  
Igg4 Level

Background & Aims: Autoimmune pancreatitis (AIP) is a fibroinflammatory condition affecting the pancreas and could present as a multisystem disorder. Diagnosis and management can pose a diagnostic challenge in certain groups of patients. We report our experience of managing this condition in a tertiary pancreaticobiliary centre in the North East of England.Methods: Patients were identified from a prospectively maintained database of patients diagnosed with AIP between 2005 and 2013. Diagnosis of definite/probable AIP was based on the revised HISORt criteria. When indicated, patients were treated with steroids and relapses were treated with azathioprine. All patients have been followed up to date.Results: Twenty-two patients were diagnosed with AIP during this period. All patients had pancreatic protocol CT performed while some patients had either MR or EUS as part of the work up. Fourteen out of 22 (64%) had an elevated IgG4 level (mean: 10.9 g/L; range 3.4 - 31 g/L). Four (18%) patients underwent surgery. Extrapancreatic involvement was seen in 15 (68%) patients, with biliary involvement being the commonest. Nineteen (86%) were treated with steroids and five (23%) required further immunosuppression for treatment of relapses. The mean follow up period was 36.94 months (range 7 - 94).Conclusion: Autoimmune pancreatitis is being increasingly recognized in the British population. Extrapancreatic involvement, particularly extrahepatic biliary involvement seems to be a frequent feature.Diagnosis should be based on accepted criteria as this significantly reduces the chances of overlooking malignancy. Awareness of this relatively rare condition and a multi-disciplinary team approach will help us to diagnose and treat this condition more efiectively thereby reducing unnecessary interventions.

Rheumatoid Arthritis- Unique Combination of Rheumatic, Cardiac and Pulmonary Manifestation of a Multisystem Disorder

2018 ◽  
Vol 4 (3) ◽  
Author(s):  
Chandan Kumar ◽  
Sandeep Aggarwal ◽  
Abhishek Abhishek ◽  
Pal Satyajit Singh Athwal ◽  
Anil Kumar Kem
Keyword(s):  
Rheumatoid Arthritis ◽  
Unique Combination ◽  
Multisystem Disorder ◽  
Pulmonary Manifestation

Cardiovascular Risk in Children with Nonalcoholic Fatty Liver Disease (NAFLD)

2020 ◽  
Vol 16 ◽  
Author(s):  
Anna Bobrus- Chociej ◽  
Natalia Wasilewska ◽  
Marta Flisiak- Jackiewicz ◽  
Dariusz Lebensztejn
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Scientific Evidence ◽  
Multisystem Disorder ◽  
Nonalcoholic Fatty Liver ◽  
Obesity Epidemic ◽  
The Metabolic Syndrome

: Nonalcoholic fatty liver disease (NAFLD) is a main cause of chronic liver disease in children. With the global obesity epidemic, the prevalence of NAFLD is increasing both in industrialized and developing countries. NAFLD is a multisystem disorder and a hepatic manifestation of the metabolic syndrome. Growing scientific evidence suggests that NAFLD is an independent risk factor for cardiovascular disease. This paper briefly describes the current knowledge concerning the association between NAFLD and cardiac dysfunction in children.

scholarly journals Comparison of Genetic Variants and Manifestations of OTUD6B-Related Disorder: The First Mexican Case

2020 ◽  
Vol 8 ◽  
pp. 232470962095777 ◽  
Author(s):  
Maria Elena Romero-Ibarguengoitia ◽  
Consuelo Cantú-Reyna ◽  
Dalia Gutierrez-González ◽  
Héctor Cruz-Camino ◽  
Arnulfo González-Cantú ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Genetic Variants ◽  
Therapeutic Approaches ◽  
Multisystem Disorder ◽  
Related Disorder ◽  
Dysmorphic Features ◽  
The Third ◽  
The Central Nervous System ◽  
Mexican Patient

The intellectual disability syndrome characterized by seizures and dysmorphic features was initially described in 2017 and was associated with genetic variants in the OTUD6B gene, identified by exome sequencing (ES) in a large cohort. This multisystem disorder primarily affects the central nervous system, the gastrointestinal, and the skeletal systems. In this article, we describe the first Mexican patient diagnosed by ES. The homozygous c.433C>T (p.Arg145*) variant of the OTUD6B gene confirmed this intellectual disability syndrome. In addition to seizures and other more frequently reported manifestations of this condition, this is the third patient with associated hypothyroidism and hypogammaglobulinemia, underscoring the value of screening for these conditions in other patients. The current challenge with this patient is to ensure medical management of his seizures and provide him with a better quality of life. The possibilities of additional therapeutic approaches may increase by understanding the physiopathology of the involved pathways.

scholarly journals Insights on autophagosome–lysosome tethering from structural and biochemical characterization of human autophagy factor EPG5

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Sung-Eun Nam ◽  
Yiu Wing Sunny Cheung ◽  
Thanh Ngoc Nguyen ◽  
Michael Gong ◽  
Samuel Chan ◽  
...  
Keyword(s):  
Biochemical Characterization ◽  
Late Endosome ◽  
Multisystem Disorder ◽  
Cytoplasmic Material ◽  
Disease Mutations ◽  
Evolutionarily Conserved ◽  
Overall Stability ◽  
Transport Vesicle ◽  
Molecular Effects

AbstractPivotal to the maintenance of cellular homeostasis, macroautophagy (hereafter autophagy) is an evolutionarily conserved degradation system that involves sequestration of cytoplasmic material into the double-membrane autophagosome and targeting of this transport vesicle to the lysosome/late endosome for degradation. EPG5 is a large-sized metazoan protein proposed to serve as a tethering factor to enforce autophagosome–lysosome/late endosome fusion specificity, and its deficiency causes a severe multisystem disorder known as Vici syndrome. Here, we show that human EPG5 (hEPG5) adopts an extended “shepherd’s staff” architecture. We find that hEPG5 binds preferentially to members of the GABARAP subfamily of human ATG8 proteins critical to autophagosome–lysosome fusion. The hEPG5–GABARAPs interaction, which is mediated by tandem LIR motifs that exhibit differential affinities, is required for hEPG5 recruitment to mitochondria during PINK1/Parkin-dependent mitophagy. Lastly, we find that the Vici syndrome mutation Gln336Arg does not affect the hEPG5’s overall stability nor its ability to engage in interaction with the GABARAPs. Collectively, results from our studies reveal new insights into how hEPG5 recognizes mature autophagosome and establish a platform for examining the molecular effects of Vici syndrome disease mutations on hEPG5.

scholarly journals Disruption of Abcc6 Transporter in Zebrafish Causes Ocular Calcification and Cardiac Fibrosis

2020 ◽  
Vol 22 (1) ◽  
pp. 278
Author(s):  
Jianjian Sun ◽  
Peilu She ◽  
Xu Liu ◽  
Bangjun Gao ◽  
Daqin Jin ◽  
...  
Keyword(s):  
Vitamin K ◽  
Cardiac Fibrosis ◽  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum ◽  
Matrix Gla Protein ◽  
Ectopic Calcification ◽  
Transcription Activator ◽  
Multisystem Disorder ◽  
Ectopic Mineralization ◽  
Extensive Calcification

Pseudoxanthoma elasticum (PXE), caused by ABCC6/MRP6 mutation, is a heritable multisystem disorder in humans. The progressive clinical manifestations of PXE are accompanied by ectopic mineralization in various connective tissues. However, the pathomechanisms underlying the PXE multisystem disorder remains obscure, and effective treatment is currently available. In this study, we generated zebrafish abcc6a mutants using the transcription activator-like effector nuclease (TALEN) technique. In young adult zebrafish, abcc6a is expressed in the eyes, heart, intestine, and other tissues. abcc6a mutants exhibit extensive calcification in the ocular sclera and Bruch’s membrane, recapitulating part of the PXE manifestations. Mutations in abcc6a upregulate extracellular matrix (ECM) genes, leading to fibrotic heart with reduced cardiomyocyte number. We found that abcc6a mutation reduced levels of both vitamin K and pyrophosphate (PPi) in the serum and diverse tissues. Vitamin K administration increased the gamma-glutamyl carboxylated form of matrix gla protein (cMGP), alleviating ectopic calcification and fibrosis in vertebrae, eyes, and hearts. Our findings contribute to a comprehensive understanding of PXE pathophysiology from zebrafish models.

scholarly journals Generation and Evaluation of Isogenic iPSC as a Source of Cell Replacement Therapies in Patients with Kearns Sayre Syndrome

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 568
Author(s):  
Glen Lester Sequiera ◽  
Abhay Srivastava ◽  
Keshav Narayan Alagarsamy ◽  
Cheryl Rockman-Greenberg ◽  
Sanjiv Dhingra
Keyword(s):  
Mononuclear Cells ◽  
Therapeutic Option ◽  
Reactive Oxygen Species Generation ◽  
Energy Deficit ◽  
Patient Specific ◽  
Multisystem Disorder ◽  
Differentiation Potential ◽  
Cell Replacement ◽  
Mtdna Mutations ◽  
Kearns Sayre Syndrome

Kearns Sayre syndrome (KSS) is mitochondrial multisystem disorder with no proven effective treatment. The underlying cause for multisystem involvement is the energy deficit resulting from the load of mutant mitochondrial DNA (mtDNA), which manifests as loss of cells and tissue dysfunction. Therefore, functional organ or cellular replacement provides a promising avenue as a therapeutic option. Patient-specific induced pluripotent stem cells (iPSC) have become a handy tool to create personalized cell -based therapies. iPSC are capable of self-renewal, differentiation into all types of body cells including cardiomyocytes (CM) and neural progenitor cells (NPC). In KSS patients, mutations in mtDNA are largely found in the muscle tissue and are predominantly absent in the blood cells. Therefore, we conceptualized that peripheral blood mononuclear cells (PBMNC) from KSS patients can be reprogrammed to generate mutation free, patient specific iPSC lines that can be used as isogenic source of cell replacement therapies to treat affected organs. In the current study we generated iPSC lines from two female patients with clinical diagnosis of classic KSS. Our data demonstrate that iPSC from these KSS patients showed normal differentiation potential toward CM, NPC and fibroblasts without any mtDNA deletions over passages. Next, we also found that functional studies including ATP production, reactive oxygen species generation, lactate accumulation and mitochondrial membrane potential in iPSC, CM, NPC and fibroblasts of these KSS patients were not different from respective cells from healthy controls. PBMNCs from these KSS patients in the current study did not reproduce mtDNA mutations which were present in muscle biopsies. Furthermore, we demonstrate for the first time that this phenomenon provides opportunities to create isogenic mutation free iPSC with absent or very low level of expression of mtDNA deletion which can be banked for future cell replacement therapies in these patients as the disease progresses.

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