Review
Gastroenterology & Hepatology
Alla Turshudzhyan, David C. Wu, George Y. Wu
Summary: Iron homeostasis is a complex process involving tightly balanced iron uptake and use. HFE gene mutations are the major cause of primary Type 1 hemochromatosis, while non-HFE hemochromatosis involves other genes such as HJV, HAMP, TFR2, and SLC40A1. Non-HFE hemochromatosis is rare but can cause severe iron overload. Diagnosis is made by ruling out HFE mutations and assessing history, physical examination, laboratory values, imaging, and liver biopsy if necessary. Early treatment with phlebotomy is important to prevent irreversible damage and chronic liver disease.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2023)
Article
Medicine, General & Internal
Tansu Eris, Ahmet Mert Yanik, Derya Demirtas, Asu Fergun Yilmaz, Tayfur Toptas
Summary: Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare genetic condition characterized by persistent hyperferritinemia without tissue iron overload, and it is often unknown to clinicians. This report presents a case of a 40-year-old woman who was misdiagnosed with hereditary hemochromatosis but was later recognized to have HHCS. The objective of this report is to increase clinical awareness about HHCS and prevent adverse medical interventions in HHCS patients.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Biology
Carmela Zizzo, Irene Ruggeri, Paolo Colomba, Christiano Argano, Daniele Francofonte, Marcomaria Zora, Emanuela Maria Marsana, Giovanni Duro, Salvatore Corrao
Summary: This paper discusses the issue of diagnostic delay in Gaucher disease and the importance of considering the possibility of Gaucher disease when encountering unexplained hyperferritinemia in a clinical case. It emphasizes the similarity in clinical features between Gaucher disease and hereditary hemochromatosis, stressing the need for careful differential diagnosis to prevent misdiagnosis and delayed treatment initiation.
Editorial Material
Hematology
Nermi L. Parrow, Robert E. Fleming
Summary: In this study, the researchers found that the hemochromatosis protein HFE is necessary for the involvement of hepatocellular transferrin receptor 1 (TFR1) in the regulation of iron metabolism and erythropoiesis. This regulation is crucial for maintaining iron balance and normal red blood cell production. The disruption of this regulation contributes to iron-loading anemias and erythropoietin resistance. The identification of the sensors responsible for these processes provides potential targets for therapeutic interventions.
Article
Genetics & Heredity
Gonzalo Hernandez, Xenia Ferrer-Cortes, Veronica Venturi, Melina Musri, Martin Floor Pilquil, Pau Marc Munoz Torres, Ines Hernandez Rodriguez, Maria Angels Ruiz Minguez, Nicholas J. Kelleher, Sara Pelucchi, Alberto Piperno, Esther Plensa Alberca, Georgina Gener Ricos, Eloi Canamero Giro, Santiago Perez-Montero, Cristian Tornador, Jordi Villa-Freixa, Mayka Sanchez
Summary: This article describes six new patients of non-HFE related hereditary hemochromatosis, with two families having novel nonsense mutations in the HFE2 gene and three families having mutations in the TFR2 gene. These rare cases highlight the importance of early molecular diagnosis in a specialized center to prevent serious clinical complications.
Article
Biochemistry & Molecular Biology
Claudia Abadia Molina, Nuria Goni Ros, Ricardo Gonzalez Tarancon, Luis Rello Varas, Valle Recasens Flores, Silvia Izquierdo Alvarez
Summary: Haemochromatosis (HC) is an inherited disorder of iron metabolism, mainly caused by mutations in the HFE gene (HC type 1). Genetic studies and analysis of biochemical parameters are important in the diagnosis of HC. Other non-HFE genes can also cause HC. The genotype may not always determine the phenotype expression in this disease.
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Hannes Hagstrom, Nelson Ndegwa, Molly Jalmeus, Mattias Ekstedt, Iris Posserud, Fredrik Rorsman, Nils Nyhlin, Daniel Klintman, Marten Werner, Hanns-Ulrich Marschall, Johan Askling, Per Stal
Summary: In Sweden, patients with HFE gene mutations were found to have an increased risk for hepatocellular carcinoma, hereditary haemochromatosis, cirrhosis, type 2 diabetes, osteoarthritis, and death during long-term follow-up, with excess mortality seen in men. No increased risk was observed for colorectal or breast cancer.
LIVER INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Olivia A. Zin, Luiza M. Neves, Daniela P. Cunha, Fabiana L. Motta, Bruna N. S. Agonigi, Dafne D. G. Horovitz, Daltro C. Almeida Jr, Jocieli Malacarne, Ana Paula S. Rodrigues, Adriana B. Carvalho, Cinthia A. Rivello, Rita Espariz, Andrea A. Zin, Juliana M. F. Sallum, Zilton F. M. Vasconcelos
Summary: Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare autosomal dominant disease caused by mutations in the FTL gene, leading to pediatric cataract and hyperferritinemia without iron overload. This case series describes three Brazilian families with HHCS, highlighting the presence of concurrent mutations in HFE gene and the need for further studies on phenotypic interactions. Whole-exome sequencing identified a likely pathogenic variant in FTL in all affected individuals, who presented with slowly progressing bilateral cataract symptoms and varying levels of hyperferritinemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Wei Zhang, Yanmeng Li, Anjian Xu, Qin Ouyang, Liyan Wu, Donghu Zhou, Lina Wu, Bei Zhang, Xinyan Zhao, Yu Wang, Xiaoming Wang, Weijia Duan, Qianyi Wang, Hong You, Jian Huang, Xiaojuan Ou, Jidong Jia
Summary: This study identified a series of novel candidate non-HFE mutations in Chinese patients with hereditary hemochromatosis, providing insights into the genetic basis of unexplained primary iron overload.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Paul Knoop, Dilay Yilmaz, Rossana Paganoni, Peter Steele-Perkins, Andreas Gruber, Banu Akdogan, Hans Zischka, Kerstin Leopold, Maja Vujic Spasic
Summary: Mutations in the HFE/Hfe gene cause Hereditary Hemochromatosis (HH), characterized by iron deposition. HFE acts in hepatocytes and myeloid cells to regulate iron homeostasis. However, HFE actions in liver-resident macrophages seem to be dispensable for cellular, hepatic, and systemic iron regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Xia Xiao, Gillian A. Moschetta, Yang Xu, Allison L. Fisher, Victor M. Alfaro-Magallanes, Som Dev, Chia-Yu Wang, Jodie L. Babitt
Summary: This study investigated the role of transferrin receptor 1 (TfR1) in cellular iron uptake and its interaction with the HFE protein to regulate hepcidin production. The results showed that hepatocyte TfR1 function depends on HFE and contributes to hepcidin suppression and iron overload in beta-thalassemia. The study also demonstrated the modulatory effect of serum iron on hepcidin regulation by hepatocyte TfR1.
Article
Biochemistry & Molecular Biology
Christine Fischer, Chiara Volani, Timea Komlodi, Markus Seifert, Egon Demetz, Lara Valente de Souza, Kristina Auer, Verena Petzer, Laura von Raffay, Patrizia Moser, Erich Gnaiger, Guenter Weiss
Summary: This study investigates the effects of dietary and genetic iron overload on mitochondrial function, revealing that iron accumulation promotes ROS production and impairs mitochondrial respiratory capacity. Differences in response to iron overload were observed in wildtype and genetic hemochromatosis model mice, suggesting the potential for iron reduction therapy to improve mitochondrial function.
Article
Genetics & Heredity
James C. Barton, J. Clayborn Barton, Ronald T. Acton
Summary: This study aimed to evaluate the height of white adults with hemochromatosis. The results showed that there was no association between HFE genotype and height in men, while women with the p.C282Y/p.C282Y genotype had a greater height. No independent association was found between HFE genotype and height in both men and women.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Cell Biology
James C. Barton, J. Clayborn Barton, Ronald T. Acton
Summary: This study examined the association between platelet counts and various factors in white adults with hemochromatosis. The results showed that platelet counts were positively associated with neutrophil, lymphocyte, and monocyte counts, as well as C-reactive protein levels. They were inversely associated with age, transferrin saturation, and hemoglobin levels. HFE genotypes were not significantly associated with platelet counts.
Article
Gastroenterology & Hepatology
Luke C. Pilling, Janice L. Atkins, David Melzer
Summary: This study found that common genetic variants may influence the disease risk for individuals carrying HFE gene mutations, including liver fibrosis, liver cancer, osteoarthritis, and diabetes.
Article
Genetics & Heredity
Matthias Baumann, Erin M. Beaver, Maria Palomares-Bralo, Fernando Santos-Simarro, Peter Holzer, Gundula Povysil, Thomas Mueller, Taras Valovka, Andreas R. Janecke
Article
Genetics & Heredity
Shuji Mizumoto, Andreas R. Janecke, Azita Sadeghpour, Gundula Povysil, Marie T. McDonald, Sheila Unger, Susanne Greber-Platzer, Kristen L. Deak, Nicholas Katsanis, Andrea Superti-Furga, Kazuyuki Sugahara, Erica E. Davis, Shuhei Yamada, Julia Vodopiutz
Article
Genetics & Heredity
Katharina M. C. Klee, Andreas R. Janecke, Hasret A. Civan, Stefan Rosipal, Peter Heinz-Erian, Lukas A. Huber, Thomas Mueller, Georg F. Vogel
Article
Genetics & Heredity
Stephanie Waich, Andreas R. Janecke, Walther Parson, Susanne Greber-Platzer, Thomas Mueller, Lukas A. Huber, Taras Valovka, Julia Vodopiutz
Article
Genetics & Heredity
Edda Haberlandt, Taras Valovka, Tanja Janjic, Thomas Muller, Georgios Blatsios, Daniela Karall, Andreas R. Janecke
Summary: This study reports a novel homozygous DOCK7 frameshift variant in adult siblings, leading to a recognizable type of epileptic encephalopathy with specific neuroimaging findings and distinctive dysmorphic features. The patients' symptoms are largely controlled by multi-pharmacotherapy, and they function on the level of 4-year-old children.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Medicine, General & Internal
Denise Aldrian, Georg F. Vogel, Teresa K. Frey, Hasret Ayyildiz Civan, Aysel Unlusoy Aksu, Yaron Avitzur, Esther Ramos Boluda, Murat Cakir, Arzu Meltem Demir, Caroline Deppisch, Hans-Christoph Duba, Gesche Dueker, Patrick Gerner, Jozef Hertecant, Jarmila Hornova, Simone Kathemann, Jutta Koeglmeier, Arsinoi Koutroumpa, Roland Lanzersdorfer, Raffi Lev-Tzion, Rosa Lima, Sahar Mansour, Manfred Meissl, Jan Melek, Mohamad Miqdady, Jorge Hernan Montoya, Carsten Posovszky, Yelena Rachman, Tania Siahanidou, Merit Tabbers, Holm H. Uhlig, Sevim Unal, Stefan Wirth, Frank M. Ruemmele, Michael W. Hess, Lukas A. Huber, Thomas Mueller, Ekkehard Sturm, Andreas R. Janecke
Summary: MYO5B plays a role in protein trafficking and recycling in cells, with mutations leading to conditions like MVID and early-onset cholestatic liver disease. The study identified new patients and mutations, providing insights into the functional consequences of MYO5B mutations.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Genetics & Heredity
Andreas R. Janecke, Xiaoqin Liu, Ruediger Adam, Sumanth Punuru, Arne Viestenz, Valeria Strauss, Martin Laass, Elizabeth Sanchez, Roberto Adachi, Martha P. Schatz, Ujwala S. Saboo, Naveen Mittal, Klaus Rohrschneider, Johanna Escher, Anuradha Ganesh, Sana Al Zuhaibi, Fathiya Al Murshedi, Badr AlSaleem, Majid Alfadhel, Siham Al Sinani, Fowzan S. Alkuraya, Lukas A. Huber, Thomas Mueller, Ruth Heidelberger, Roger Janz
Summary: New STX3 variants have been found to be associated with a syndrome including congenital enteropathy and retinal dystrophy. These variants affect STX3 transcripts, leading to reduced numbers of photoreceptors and thinning of cell layers.
Article
Medicine, General & Internal
Michael W. Hess, Iris M. Krainer, Przemyslaw A. Filipek, Barbara Witting, Karin Gutleben, Ilja Vietor, Heinz Zoller, Denise Aldrian, Ekkehard Sturm, James R. Goldenring, Andreas R. Janecke, Thomas Mueller, Lukas A. Huber, Georg F. Vogel
Summary: The study thoroughly characterized the ultrastructural and immuno-cytochemical phenotype of hepatocytes and duodenal enterocytes from a unique case of an adult MYO5B-PFIC patient. Advanced methods were used in combination with standard procedures to reveal various abnormalities related to this rare disease.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Clinical Neurology
Pauline E. Schneeberger, Sheela Nampoothiri, Tess Holling, Dhanya Yesodharan, Malik Alawi, A. S. Knisely, Thomas Mueller, Barbara Plecko, Andreas R. Janecke, Kerstin Kutsche
Summary: GARP and EARP are membrane-tethering heterotetramers located at the trans-Golgi network and recycling endosomes, mediating retrograde transport and endocytic recycling. Patients with VPS50 variants exhibit severe developmental delay, microcephaly, seizures, and liver abnormalities.
Article
Pediatrics
Hasret Ayyildiz Civan, Coleen Leitner, Iris Oestreicher, Anna-Maria Schneider, Malte Cremer, Johannes A. Mayr, Rainer Rossi, Thomas Mueller, Andreas R. Janecke
Summary: Tufting enteropathy is caused by recessive EPCAM mutations, resulting in congenital diarrhea and disorganization of enterocytes. The study found that patients with TE experienced adequate weight gain with PN but often had stunted growth, with diagnosis typically being delayed.
Article
Genetics & Heredity
Sandy Siegert, Gabriel T. Mindler, Christof Bruecke, Andreas Kranzl, Janina Patsch, Markus Ritter, Andreas R. Janecke, Julia Vodopiutz
Summary: This study reports on three adult siblings homozygous for the FAM149B1 variant, showing a phenotype of mainly neurological and skeletal ciliopathy with predominant oculomotor dysfunction. Despite presenting with symptoms since birth, these individuals have stable outcomes with normal retinal, renal, and liver function, highlighting the importance of extended clinical and genetic studies in families with complex phenotypes.
Article
Genetics & Heredity
Ema Bogdanic, Thomas Mueller, Peter Heinz-Erian, Dorota Garczarczyk-Asim, Andreas R. Janecke, Aline Rueckel
Summary: This study reported a patient with congenital sodium diarrhea, identified novel compound heterozygous variants in the SLC9A3 gene, and indicated that the clinical phenotype of the patient is milder compared to known CSD spectrum.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Pediatrics
Anna M. Kavallar, Franka Messner, Stefan Scheidl, Rupert Oberhuber, Stefan Schneeberger, Denise Aldrian, Valeria Berchtold, Murat Sanal, Andreas Entenmann, Simon Straub, Anna Gasser, Andreas R. Janecke, Thomas Mueller, Georg F. Vogel
Summary: This case report presents three cases of PFIC1 patients who underwent LT and successfully resolved graft inflammation and steatosis by using terminal ileum SBD.
Article
Genetics & Heredity
Julia Vodopiutz, Lisa-Maria Steurer, Florentina Haufler, Franco Laccone, Dorota Garczarczyk-Asim, Matthias Hilkenmeier, Philipp Steinbauer, Andreas R. Janecke
Summary: SHOX deficiency is a common genetic cause of short stature. It can lead to Leri-Weill dyschondrosteosis and nonspecific short stature. This study reports the pseudo-autosomal recessive inheritance of Leri-Weill dyschondrosteosis in two siblings caused by a novel homozygous non-canonical splice-site variant in the SHOX gene. This study expands the understanding of the molecular and inheritance spectrum of SHOX deficiency.
Article
Genetics & Heredity
Ferda O. Hosnut, Andreas R. Janecke, Gulseren Sahin, Georg F. Vogel, Naz G. Lafci, Paul Bichler, Thomas Mueller, Lukas A. Huber, Taras Valovka, Aysel U. Aksu
Summary: Congenital glucose-galactose malabsorption is a rare autosomal recessive disorder caused by mutations in SLC5A1 gene. Our study reports clinical and molecular data from 11 affected individuals in four unrelated Turkish families. Two novel SLC5A1 missense variants, p.Gly43Arg and p.Ala92Val, were identified in two families and linked to the disease. Our findings expand the mutational spectrum of this rare disorder.