Inherited liver disease

Nina Ondruskova, Tomas Honzik, Alzbeta Vondrackova, Viktor Stranecky, Marketa Tesarova, Jiri Zeman, Hana Hansikova
Congenital disorders of glycosylation (CDG) represent a wide range of >140 inherited metabolic diseases, continually expanding not only with regards to the number of newly identified causative genes, but also the heterogeneity of the clinical and molecular presentations within each subtype. The deficiency of ATP6AP1, an accessory subunit of the vacuolar H+ -ATPase, is a recently characterized N- and O-glycosylation defect manifesting with immunodeficiency, hepatopathy and cognitive impairment. At the cellular level, the latest studies demonstrate a complex disturbance of metabolomics involving peroxisomal function and lipid homeostasis in the patients...
March 26, 2020: Journal of Inherited Metabolic Disease
Mariano Piazzolla, Nicola Castellaneta, Antonio Novelli, Emanuele Agolini, Dario Cocciadiferro, Leonardo Resta, Loren Duda, Michele Barone, Enzo Ierardi, Alfredo Di Leo
BACKGROUND: Benign recurrent intrahepatic cholestasis is a genetic disorder with recurrent cholestatic jaundice due to ATP8B1 and ABCB11 gene mutations encoding for hepato-canalicular transporters. Herein, we firstly provide the evidence that a nonsense variant of ATP8B1 gene (c.1558A>T) in heterozygous form is involved in BRIC pathogenesis. CASE SUMMARY: A 29-year-old male showed severe jaundice and laboratory tests consistent with intrahepatic cholestasis despite normal gamma-glutamyltranspeptidase...
February 27, 2020: World Journal of Hepatology
Effrosyni Koutsouraki, Dimitrios Michmizos, Olga Patsi, John Tzartos, Martha Spilioti, Marianthi Arnaoutoglou, Magda Tsolaki
BACKGROUND: To the best of our knowledgedd, there is currently no case in the literature reporting the comorbidity of Wilson's and Creutzfeldt-Jakob disease (CJD), linked through copper. CASE PRESENTATION: A 44-year-old male with a history of inherited Wilson's disease (hepatolenticular degeneration), which manifested as mild liver injury and psychiatric symptoms, was admitted to our department due to speech and cognitive disturbances. Upon his admission, he had motor aphasia as well as psychomotor retardation with an otherwise normal neurological examination...
March 13, 2020: Virology Journal
Jean Pierre Salles
Hypophosphatasia (HPP) is a rare inherited systemic metabolic disease caused by mutations in the tissue-nonspecific alkaline phosphatase ( TNSALP ) gene. TNSALP is expressed in the liver, kidney and bone, and its substrates include TNSALP inorganic pyrophosphate, pyridoxal-5'-phosphate (PLP)/vitamin B6 and phosphoethanolamine (PEA). Autosomal recessive and dominant forms of the disease result in a range of clinical entities. Major hallmarks are low alkaline phosphatase (ALP) and elevated PLP and PEA levels...
February 2020: Clinical Biochemist. Reviews
J Chavany, A Cano, B Roquelaure, P Bourgeois, J Boubnova, P Gaignard, C Hoebeke, R Reynaud, B Rhomer, A Slama, C Badens, B Chabrol, A Fabre
Acute liver failure (ALF) in childhood is a life-threatening emergency. ALF is often caused by drug toxicity, autoimmune hepatitis, inherited metabolic diseases, and infections. However, despite thorough investigations, a cause cannot be determined in approximately 50% of cases. Here, we report three cases with recurrent ALF caused by NBAS and SCYL1 pathogenic variants. These patients did not present with any other phenotypic sign usually associated with NBAS and SCYL1 pathogenic variants. Two of them underwent liver transplantation and are healthy without recurrence of ALF...
March 4, 2020: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Younis Al Mufargi, Asim Qureshi, Abdullah Al Asmi
Lafora disease is a rare, genetic, glycogen metabolism disorder inherited as autosomal recessive characterized by the presence of inclusion bodies, known as Lafora bodies, within the cytoplasm of the cells in the heart, liver, muscle, and skin. Lafora disease presents as a neurodegenerative disorder that causes impairment in the development of cerebral cortical neurons. We present here a case of Lafora disease that presented with progressive myoclonus epilepsy (PME) and investigated at our center. She was diagnosed to have Lafora disease with typical histological findings on skin biopsy and was found to be positive for the pathogenic mutation on genetic testing...
January 28, 2020: Curēus
Odunayo S Lawal, Nimisha Mathur, Srilatha Eapi, Rupak Chowdhury, Bilal Haider Malik
Shwachman-Diamond syndrome (SDS) is an autosomal recessive inherited disease of the SBDS gene. It has multi-organ involvement but primarily affects the bone marrow and the pancreas. This disease is more commonly found in males than females, and its earliest manifestation in infancy is pancytopenia, most especially neutropenia. Our article attempts an in-depth analysis of the hepatic and cardiac association in this disease and the severity of this association. For the purpose of this study, we engaged in an in-depth research of critically appraised literature and published articles...
January 16, 2020: Curēus
Gregory M Pastores, Derralynn A Hughes
Lysosomal acid lipase (LAL) deficiency is a metabolic (storage) disorder, encompassing a severe (Wolman disease) and attenuated (Cholesterol ester storage disease) subtype; both inherited as autosomal recessive traits. Cardinal clinical features include the combination of hepatic dysfunction and dyslipidemia, as a consequence of cholesteryl esters and triglyceride accumulation, predominately in the liver and vascular and reticuloendothelial system. Significant morbidity can arise, due to liver failure and/or atherosclerosis; in part related to the severity of the underlying gene defect and corresponding enzyme deficiency...
2020: Drug Design, Development and Therapy
Motasim M Jawi, Jiri Frohlich, Sammy Y Chan
Lipoprotein(a) [Lp(a)], aka "Lp little a", was discovered in the 1960s in the lab of the Norwegian physician Kåre Berg. Since then, we have greatly improved our knowledge of lipids and cardiovascular disease (CVD). Lp(a) is an enigmatic class of lipoprotein that is exclusively formed in the liver and comprises two main components, a single copy of apolipoprotein (apo) B-100 (apo-B100) tethered to a single copy of a protein denoted as apolipoprotein(a) apo(a). Plasma levels of Lp(a) increase soon after birth to a steady concentration within a few months of life...
2020: Journal of Lipids
Ryan P Thompson, Eric Nilsson, Michael K Skinner
Epigenetics refers to molecular factors and processes around DNA that can affect genome activity and gene expression independent of DNA sequence. Epigenetic mechanisms drive developmental processes and have also been shown to be tied to disease development. Many epigenetic studies have been done using plants, rodent, and human models, but fewer have focused on domestic livestock species. The goal of this review is to present current epigenetic findings in livestock species (cattle, pigs, sheep and poultry)...
February 18, 2020: Animal Reproduction Science
Hana Carolina Moreira Farnezi, Ana Carolina Xavier Goulart, Adriana Dos Santos, Mariana Gontijo Ramos, Maria Lectícia Firpe Penna
The mitochondria are intracellular organelles, and just like the cell nucleus they have their own genome. They are extremely important for normal body functioning and are responsible for ATP production - the main energy source for the cell. Mitochondrial diseases are associated with mutations in mitochondrial DNA and are inherited exclusively from the mother. They can affect organs that depend on energy metabolism, such as skeletal muscles, the cardiac system, the central nervous system, the endocrine system, the retina and liver, causing various incurable diseases...
February 19, 2020: JBRA Assisted Reproduction
Marcin Krawczyk, Roman Liebe, Frank Lammert
Non-alcoholic fatty liver disease (NAFLD) is on the verge of becoming the leading cause of liver disease. NAFLD develops at the interface between environmental factors and inherited predisposition. Genome-wide association studies, followed by exome-wide analyses, led to identification of genetic risk variants (e.g. PNPLA3, TM6SF2, SERPINA1) and key pathways involved in fatty liver disease pathobiology. Functional studies improved our understanding of these genetic factors and the molecular mechanisms underlying the trajectories from fat accumulation to fibrosis, cirrhosis and cancer over time...
February 14, 2020: Gastroenterology
A Kovacevic, S F Garbade, G F Hoffmann, M Gorenflo, S Kölker, C Staufner
BACKGROUND: Propionic acidemia (PA) is an organic aciduria caused by inherited deficiency of propionyl-CoA carboxylase. Left ventricular dysfunction and QT prolongation may lead to life-threatening complications. Systematic analyses of cardiac phenotypes, in particular effects of specific cardiac therapies, are scarce. METHODS: In this longitudinal observational monocentric study (data from 1989 to 2017) all PA patients treated at our center were included. Echocardiographic parameters (left ventricular end-diastolic diameter: LVEDD, left ventricular shortening fraction, mitral valve Doppler inflow pattern) and 12‑lead electrocardiogram recordings (corrected QT interval: QTc) were analyzed...
February 10, 2020: Molecular Genetics and Metabolism
Sibtain Ahmed, Bushra Afroze
The glycogen storage diseases (GSDs) are a group of inherited metabolic disorders that result from a defect in any one of several enzymes required for either glycogen synthesis or glycogen degradation. The traditional diagnostic approach is based on the invasive hepatic or muscle biopsies, which are neither cost effective nor convenient. Molecular (gene testing) has emerged over the course of past few years as a robust alternative diagnostic tool, which not only confirms the diagnosis of GSDs but also clearly differentiates the types of GSDs allowing the initiation of the type-specific appropriate treatment for the particular type of GSDs...
January 2020: Pakistan Journal of Medical Sciences Quarterly
Hedwig S Kruitwagen, Loes A Oosterhoff, Monique E van Wolferen, Chen Chen, Sathidpak Nantasanti Assawarachan, Kerstin Schneeberger, Anne Kummeling, Giora van Straten, Ies C Akkerdaas, Christel R Vinke, Frank G van Steenbeek, Leonie W L van Bruggen, Jeannette Wolfswinkel, Guy C M Grinwis, Sabine A Fuchs, Helmuth Gehart, Niels Geijsen, Robert G Vries, Hans Clevers, Jan Rothuizen, Baukje A Schotanus, Louis C Penning, Bart Spee
The shortage of liver organ donors is increasing and the need for viable alternatives is urgent. Liver cell (hepatocyte) transplantation may be a less invasive treatment compared with liver transplantation. Unfortunately, hepatocytes cannot be expanded in vitro, and allogenic cell transplantation requires long-term immunosuppression. Organoid-derived adult liver stem cells can be cultured indefinitely to create sufficient cell numbers for transplantation, and they are amenable to gene correction. This study provides preclinical proof of concept of the potential of cell transplantation in a large animal model of inherited copper toxicosis, such as Wilson's disease, a Mendelian disorder that causes toxic copper accumulation in the liver...
February 11, 2020: Cells
Michele Alves-Bezerra, Nika Furey, Collin G Johnson, Karl-Dimiter Bissig
CRISPR/Cas9 gene editing has revolutionised biomedical research. The ease of design has allowed many groups to apply this technology for disease modelling in animals. While the mouse remains the most commonly used organism for embryonic editing, CRISPR is now increasingly performed with high efficiency in other species. The liver is also amenable to somatic genome editing, and some delivery methods already allow for efficient editing in the whole liver. In this review, we describe CRISPR-edited animals developed for modelling a broad range of human liver disorders, such as acquired and inherited hepatic metabolic diseases and liver cancers...
November 2019: JHEP reports: innovation in hepatology
Jack Dummer, Claudia C Dobler, Mark Holmes, Daniel Chambers, Ian A Yang, Lianne Parkin, Sheree Smith, Peter Wark, Anouk Dev, Sandra Hodge, Eli Dabscheck, Julian Gooi, Sameh Samuel, Steven Knowles, Anne E Holland
AATD is a common inherited disorder associated with an increased risk of developing pulmonary emphysema and liver disease. Many people with AATD-associated pulmonary emphysema remain undiagnosed and therefore without access to care and counselling specific to the disease. AAT augmentation therapy is available and consists of i.v. infusions of exogenous AAT protein harvested from pooled blood products. Its clinical efficacy has been the subject of some debate and the use of AAT augmentation therapy was recently permitted by regulators in Australia and New Zealand, although treatment is not presently subsidized by the government in either country...
February 6, 2020: Respirology: Official Journal of the Asian Pacific Society of Respirology
Janine Petters, Chiara Cimmaruta, Katharina Iwanov, Matthew L Chang, Christin Völkner, Gudrun Knuebel, Hugo Murua Escobar, Moritz J Frech, Andreas Hermann, Arndt Rolfs, Jan Lukas
Wilson disease (WD) is an inherited, autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene. Pathogenic single nucleotide variants (SNVs) lead to functional impairment of the copper transporting ATPase ATP7B, resulting in copper accumulation and toxicity in the liver and brain. We describe the generation of two induced pluripotent stem cell (iPSC) lines derived from fibroblasts of two female WD patients. Patient 1 is compound heterozygous for p.E1064A and p.H1069Q. Patient 2 is homozygous for p...
January 27, 2020: Stem Cell Research
Joanna Walczak-Sztulpa, Renata Posmyk, Ewelina M Bukowska-Olech, Anna Wawrocka, Aleksander Jamsheer, Machteld M Oud, Miriam Schmidts, Heleen H Arts, Anna Latos-Bielenska, Anna Wasilewska
BACKGROUND: Sensenbrenner syndrome, which is also known as cranioectodermal dysplasia (CED), is a rare, autosomal recessive ciliary chondrodysplasia characterized by a variety of clinical features including a distinctive craniofacial appearance as well as skeletal, ectodermal, liver and renal anomalies. Progressive renal disease can be life-threatening in this condition. CED is a genetically heterogeneous disorder. Currently, variants in any of six genes (IFT122, WDR35, IFT140, IFT43, IFT52 and WDR19) have been associated with this syndrome...
February 1, 2020: Orphanet Journal of Rare Diseases
Peter C Cooper, Anna Pavlova, Gary W Moore, Kieron P Hickey, Richard A Marlar
Inherited protein C (PC) deficiency increases risk of venous thromboembolism (VTE) by 5 to 10-fold in thrombosis-prone families; however, heterozygous PC deficiency alone does not determine that a subject has thrombophilia. Protein C deficient subjects, who lack additional inherited risk factors such as factor V Leiden or have no major acquired risk factors, may not suffer from VTE. In addition, PC deficiency may be acquired, often due to vitamin K antagonist treatment or liver disease. In contrast, homozygous or compound heterozygous PC deficiencies are rare and serious disorders, and affected infants are often in families with no history of PC deficiency or thrombosis...
February 2020: Journal of Thrombosis and Haemostasis: JTH
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