scholarly journals A novel compound heterozygous variant in NBAS causing bone fragility by the type of osteogenesis imperfecta

2020 ◽  
pp. 52-53
Author(s):  
Д.А. Петухова ◽  
Е.Е. Гуринова ◽  
А.Л. Сухомясова ◽  
Н.Р. Максимова
Keyword(s):  
Connective Tissue ◽  
Osteogenesis Imperfecta ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Clinical Signs ◽  
Connective Tissue Diseases ◽  
Bone Fragility ◽  
Compound Heterozygous ◽  
Heterozygous Variant ◽  
Panel Sequencing

В статье представлены клинические, молекулярно-генетические характеристики 6-летнего пациента с клиническими признаками SOPH-синдрома, печеночной недостаточностью, а также хрупкостью костей по типу несовершенного остеогенеза. В результате массового параллельного секвенирования были обнаружены описанная мутация с.5741G>A (p.Arg1914His) и ранее не описанный миссенс-вариант c.2535G>T (p.Trp845Cys) гена NBAS в компаунд-гетерозиготном состоянии. Here, we describe a case of a 6-year-old Yakut girl who presented with clinical signs of SOPH syndrome, acute liver failure (ALF) and bone fragility by the type of osteogenesis imperfecta. Targeted panel sequencing for 494 genes of connective tissue diseases of the patient revealed that he carried novel compound heterozygous missense mutation in NBAS, c.2535G>T (p.Trp845Cys), с.5741G>A (p.Arg1914His).

Novel compound heterozygous variants in the NBAS gene in a child with osteogenesis imperfecta and recurrent acute liver failure

2021 ◽  
Vol 14 (2) ◽  
pp. e234993
Author(s):  
Sowmya Krishnan ◽  
Ankur Rughani ◽  
Anne Tsai ◽  
Sirish Palle
Keyword(s):  
Osteogenesis Imperfecta ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Autosomal Recessive ◽  
Retrograde Transport ◽  
Compound Heterozygous ◽  
X Rays ◽  
Multiple Fractures ◽  
Therapeutic Implications ◽  
Compound Heterozygous Variants

Osteogenesis imperfecta (OI) consists of a group of genetically and phenotypically heterogeneous diseases characterised by bone fragility. Recent improvement in gene sequencing methods has helped us identify rare forms of OI that are inherited in an autosomal recessive manner. Paediatric endocrinology was consulted on a newborn girl with multiple fractures and wavy thin ribs noted on X-rays. In addition to the bone phenotype, she also has short stature and recurrent acute liver failure (ALF) episodes triggered by intercurrent illness. Whole exome sequencing revealed two novel compound heterozygous variants in neuroblastoma amplified sequence (NBAS) gene. NBAS gene codes for a protein that is involved in nonsense-mediated decay pathway and retrograde transport of proteins from Golgi to endoplasmic reticulum. Recognition of pathogenic variants in this gene as a rare cause of autosomal recessive OI and recurrent ALF has important therapeutic implications.

Characterization of a complex phenotype (fever-dependent recurrent acute liver failure and osteogenesis imperfecta) due to NBAS and P4HB variants

2021 ◽  
Author(s):  
Francisco Javier Cotrina-Vinagre ◽  
María Elena Rodríguez-García ◽  
Elena Martín-Hernández ◽  
Cristina Durán-Aparicio ◽  
Abraham Merino-López ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Complex Phenotype

scholarly journals AB0815 FIRST DEGREE RELATIVES OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS - CLINICAL, SEROLOGICAL AND IMMUNOLOGICAL CORRELATIONS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1432.2-1432
Author(s):  
B. Penev ◽  
G. Vasilev ◽  
D. Kyurkchiev ◽  
S. Monov
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Connective Tissue ◽  
Lupus Erythematosus ◽  
Current Knowledge ◽  
Statistical Significance ◽  
Clinical Signs ◽  
Connective Tissue Diseases ◽  
Pharmaceutical Products ◽  
Systemic Lupus

Background:Antinuclear antibodies (ANA) have been unequivocally recognized as essential for diagnosis and play both pathogenic and diagnostic roles in systemic lupus erythematosus (SLE). SLE and ANA have also been found to be more often among relatives of SLE patients. ANA and other immunological changes are known to appear prior to the clinical onset of the disease and thus can be used as predictors. Studies have reported that relatives of SLE patients who later transitioned to SLE displayed more lupus-associated autoantibody specificities and had early clinical signs. They also displayed elevated baseline plasma levels of inflammatory mediators, including B-lymphocyte stimulator (BLyS) and interferon-associated chemokines, with concurrent decreases in levels of regulatory mediators, e.g. tumor growth factor (TGF)-β. Commonly recognized risk factors for SLE are signs of past Epstein-Barr (EBV) infection, use of estrogen drugs and current smoking. It seems that ANA, immunologic changes and risk factors have not been investigated together in relatives of SLE patients.Objectives:The aim of the study was to determine the relative prevalence of clinical signs of SLE or connective tissue disease (CTD), smoking, use of estrogen drugs and levels of circulating ANA, BLyS, IFN-α, TGF-β, anti-EBV viral capsid antigen (VCA) IgM and IgG antibodies among sera of FDR, non-FDR healthy individuals and SLE patients.Methods:Forty three FDRs of SLE patients were studied along with 15 SLE patients and 15 clinically healthy subjects as control groups. The FDRs and the healthy answered a questionnaire about early clinical signs of CTD, smoking and estrogen use history. The questionnaire was developed based on the existing Screening Questionnaire for Connective Tissue Diseases and current knowledge of most early signs of CTD. Blood samples were obtained and tested for ANA, both by indirect immunofluorescence and immunoblot, anti-dsDNA by ELISA. ELISA was also performed to measure levels of BLys, IFN-α, TGF-β, anti-EBV IgM and IgG.Results:More than half of the FDRs displayed ANA in titer 1:160 or more, with predominately AC-4 type of fluorescence according to International Classification on ANA Patterns (ICAP) compared to only AC-1 and AC-0 among patients and controls respectively. A correlation between the ANA titer and the number of complaints was found. This was particularly valid or reported skin complaints and oral ulcers which appeared more frequently when ANA was 1:320 or above (p=0,018 and 0,038 respectively). Furthermore, oral ulcerations showed positive correlation with the presence of anti-Ro60. No associations were found in the healthy group between reported complaints and ANA titers. Smoking and estrogen use did not differ across the three groups. Patients showed significant differences in levels of BLys (p=0,027), TGF-β (p=0,019) and anti-EBV IgG (p=0.041) compared to both FDRs and controls. Without reaching statistical significance, levels of TGF-β tend to split the FDR group into “healthy-like” and “SLE-like”.Conclusion:Our results show that FDR ANA levels are between those of SLE patients and healthy subject groups. This is consistent with previous studies. The data also suggest that ANA positivity correlates with reported complaints, some of which could be interpreted as very early clinical signs of SLE. Of note, anti-Ro60 is known to be among the earliest ANA that appear in “future” SLE patients and in this study they are related to oral complaints that could be caused by early sicca phenomena. Immunologically, our data support previous findings [1] that the FDRs are a heterogenic group with different “lupus-developing” potential.References:[1]Munroe МE. et al, Soluble Mediators and Clinical Features Discern Risk of Transitioning to Classified Disease in Relatives of Systemic Lupus Erythematosus Patients, Arthritis Rheumatol. 2017 March; 69(3): 630–642.Disclosure of Interests:Bogdan Penev: None declared, Georgi Vasilev: None declared, Dobroslav Kyurkchiev: None declared, Simeon Monov Speakers bureau: I have been paid for giving lectures on statistical data on efficacy of many pharmaceutical products on various companies

scholarly journals Glutamine synthetase expression in the brain during experimental acute liver failure (immunohistochemical study)

2021 ◽  
Vol 11 (10) ◽  
pp. 342-356
Author(s):  
T. Shulyatnikova ◽  
V. Tumanskiy
Keyword(s):  
White Matter ◽  
Glutamine Synthetase ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Caudate Nucleus ◽  
Immunohistochemical Study ◽  
Clinical Signs ◽  
Brain Regions ◽  
Progressive Increase ◽  
The Brain

The aim of the study was to determine the immunohistochemical level of glutamine synthetase (GS) expression in different brain regions in the conditions of experimental acute liver failure in rats. Materials and methods. The study was conducted in Wistar rats: 5 sham (control) animals and 10 rats with acetaminophen induced liver failure model (AILF). The immunohistochemical study of GS expression in the sensorimotor cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen was carried out in the period of 12-24 h after acetaminophen treatment. Results. Beginning from the 6th hour after acetaminophen treatment all AILF-animals showed the progressive increase in clinical signs of acute brain disfunction finished in 6 rats by comatose state up to 24 h - they constituted subgroup AILF-B, “non-survived”. 4 animals survived until the 24 h - subgroup AILF-A, “survived”. In the AILF-B group, starting from 16 to 24 hours after treatment, a significant (relative to control) regionally-specific dynamic increase in the level of GS expression was observed in the brain: in the cortex – by 307.33 %, in the thalamus – by 249.47%, in the hippocampus – by 245.53%, in the subcortical white matter – by 126.08%, from 12th hour – in the caudate nucleus/putamen, by 191.66 %; with the most substantive elevation of GS expression in the cortex: by 4.07 times. Conclusion. Starting from the 16th hours after the acetaminophen treatment (from the 12th h in the caudate nucleus/putamen region) and up to 24 h, it is observed reliable compared to control dynamic increase in GS protein expression in the cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen of the rat brain with the most significant elevation in the cortex among other regions. The heterogeneity in the degree of GS expression rising in different brain regions potentially may indicate regions more permeable for ammonia and/or other systemic toxic factors as well as heterogeneous sensitivity of brain regions to deleterious agents in conditions of AILF. Subsequently, revealed diversity in the GS expression reflects the specificity of reactive response of local astroglia in the condition of AILF-encephalopathy during specific time-period. The dynamic increase in the GS expression associated with impairment of animal state, indicates involvement of increased GS levels in the mechanisms of experimental acute hepatic encephalopathy.

scholarly journals COVID-19: a fatal case of acute liver failure associated with SARS-CoV-2 infection in pre-existing liver cirrhosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jana Ihlow ◽  
Alexander Seelhoff ◽  
Victor M. Corman ◽  
Achim D. Gruber ◽  
Simon Dökel ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Damage ◽  
Cathepsin L ◽  
Fatal Case ◽  
Clinical Signs ◽  
Angiotensin Converting Enzyme 2 ◽  
Severe Liver Damage ◽  
Severe Jaundice ◽  
Transmembrane Serine Protease

Abstract Background The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism. Case presentation Here, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2). Conclusion Our findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice.

scholarly journals Novel Mutation in GALT Gene in Galactosemia Patient with Group B Streptococcus Meningitis and Acute Liver Failure

Medicina ◽  
2019 ◽  
Vol 55 (4) ◽  
pp. 91 ◽  
Author(s):  
Alina Grama ◽  
Ligia Blaga ◽  
Alina Nicolescu ◽  
Călin Deleanu ◽  
Mariela Militaru ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Screening Program ◽  
Novel Mutation ◽  
Group B Streptococcus ◽  
Compound Heterozygous ◽  
Classic Galactosemia ◽  
Short Period ◽  
Galt Gene ◽  
Group B

Classic galactosemia is an autosomal recessive disorder caused by the deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT) involved in galactose metabolism. Bacterial infections are a known cause of early morbidity and mortality in children with classic galactosemia. The most common agent is Escherichia coli, but in rare situations, other bacteria are incriminated. We report a case of a three-week-old female patient with galactosemia, who presented with Group B Streptococcus (GBS) meningitis/sepsis. She received treatment with antibiotics, supportive therapy, and erythrocyte transfusion, but after a short period of improvement, she presented acute liver failure with suspicion of an inborn error of metabolism. Rapid nuclear magnetic resonance (NMR) spectroscopy from urine showed highly elevated values of galactose and galactitol. Under intensive treatment for acute liver failure and with a lactose-free diet, her clinical features and laboratory parameters improved considerably. Genetic testing confirmed compound heterozygous status for GALT mutations: c.563 A>G [p.Q188R] and c. 910 C>T, the last mutation being a novel mutation in GALT gene. In countries without an extensive newborn screening program, a high index of suspicion is necessary for early diagnosis and treatment of galactosemia.

scholarly journals Applying the Molecular Adsorbent Recirculating System (MARS) in the Treatment of Acute Liver Failure (ALF) Case Report

2018 ◽  
Vol 19 (2) ◽  
pp. 189-194
Author(s):  
Jagoda Gavrilovic ◽  
Jelena Djordjevic Velickovic ◽  
Zeljko Mijailovic ◽  
Tatjana Lazarevic ◽  
Aleksandar Gavrilovic ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Clinical Signs ◽  
Caucasian Woman ◽  
Coagulation Disorder ◽  
Liver Support ◽  
Molecular Adsorbent Recirculating System ◽  
Extracorporeal Liver Support ◽  
Molecular Adsorbent

Abstract Acute liver failure (ALF) is a rare but life-threatening illness with multiple organ failure. The short-term mortality rate exceeded 80 % despite modern approaches in treatment. Drugs, infections by hepatic viruses and toxins are the most common causes of ALF. Progressive jaundice, coagulation disorder and hepatic encephalopathy are dominated as a clinical signs of the illness. We present a case of a 36-year-old Caucasian woman hospitalized in ICU due to yellow discoloration of the skin and sclera, severe disseminated coagulopathy and hemodynamic instability. ALF is developed due to Hepatitis B Virus infection, resulting in hepatic toxicity as well as coma. General condition rapidly improved after applying of Molecular Adsorbent Recirculating System (MARS), an extracorporeal liver support system based on albumin dialysis. It is relatively expensive treatment that is used for the patient with hepatic encephalopathy grade 3 or 4 in our institution. In conclusion, an early administration of MARS significantly reveals subjective and objective clinical improvement in the case we presented.

scholarly journals The study of albumin dialysis efficiency in acute liver failure using the «Bioartificial liver» device

2015 ◽  
Vol 96 (5) ◽  
pp. 768-771
Author(s):  
E E Polevshchikova
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Biochemical Markers ◽  
Clinical Signs ◽  
Human Albumin ◽  
Bioartificial Liver ◽  
Experimental Sample ◽  
Albumin Solution ◽  
Albumin Dialysis ◽  
Bioartificial Liver Device

Aim. Clinical testing of albumin dialysis method in patients with acute liver failure of different etiologies on the experimental sample of the «bioartificial liver» device. Methods. Clinical assessment of treatment using the «bioartificial liver» device was conducted on 20 patients aged 22-68 years old who had acute liver failure of different etiology. The «bioartificial liver» device consisted of a perfusion unit, the dialyzer, dialysis circuit with albumin solution and carbon haemosorbent mode. A 10% donor human albumin solution was used as the dialysis fluid in recirculation mode. For restoration of the accepting ability albumin was exposed to perfusion through the carbonic hemosorbent. Duration of the treatment was 3 hours, control of liver damage biochemical markers was performed before and after the session. Results. There was a statistically significant reduction in biochemical markers of cytolysis and cholestasis: transaminases, alkaline phosphatase and bilirubin levels. We also observed a statistically significant reduction of ammonia level, which is one of the main clinical and laboratory signs characterizing the severity of encephalopathy. Improvement of liver synthetic function reflected a statistically significant increase in glucose level. Clinical stabilization as well as reduction of encephalopathy clinical signs were observed after the procedure. No side effects were notices. Conclusion. Implementation of albumin dialysis in patients with acute liver failure using the «bioartificial liver» device was accompanied by an improvement of their functional state. This gives reason to use this method for the treatment of acute liver failure in intensive care units.

scholarly journals Insights into the management of Wilson’s disease

2017 ◽  
Vol 10 (11) ◽  
pp. 889-905 ◽  
Author(s):  
Mohmadshakil Kathawala ◽  
Gideon M. Hirschfield
Keyword(s):  
Liver Disease ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Clinical Features ◽  
Wilson’S Disease ◽  
Early Recognition ◽  
Clinical Signs ◽  
Wilson's Disease ◽  
Biochemical Tests ◽  
Causative Gene

Wilson’s disease is a rare, inherited autosomal recessive disease of copper metabolism, in which the causative gene, ATP7B, results in absent or reduced function of the ATP7B transporter important for biliary excretion of copper and incorporation of copper into caeruloplasmin. Affected patients accumulate excessive copper within the liver, brain and other tissues. A disease mainly of children, adolescents and young adults; clinical features vary from the asymptomatic state to chronic liver disease, acute liver failure, and neuropsychiatric manifestations. Diagnosis requires a high index of suspicion and is based on a combination of clinical signs, biochemical tests, hepatic copper content assay and mutation analysis of the ATP7B gene; to date, there are more than 500 mutations of ATP7B in patients with Wilson’s disease. Early recognition and treatment can result in an excellent prognosis whereas untreated disease is almost always fatal. Drug therapies include chelating agents, such as penicillamine or trientine, and zinc salts. Liver transplantation is curative correcting the underlying pathophysiology and is traditionally indicated in acute liver failure or end-stage liver disease refractory to medical therapy. This review provides an overview of various aspects of Wilson’s disease including molecular basis of the disease, clinical features, diagnostic and management strategies with their current limitations.

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