The Iron-man : A case-report

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn Skoða/Opna(view/open)The most common cause of microcytic anemia is iron deficiency. We report a 29 year old man with history of dyspnea, fatigue and severe microcytic anemia despite iron therapy for 3 years. Blood transfusions elevated the hemoglobin levels temporarily, but iv iron did not. Bone marrow showed sideroblastic anemia. The anemia resolved with pyridoxine treatment but severe iron overload necessitated multiple phlebotomies. Today the patient is asymptomatic on pyridoxine with a normal hemoglobin level.Algengasta orsök smáfrumublóðleysis er járnskortur. Sagt er frá 29 ára manni sem hafði verið með mæði, slappleika og svæsið smáfrumublóðleysi í þrjár vikur þrátt fyrir þriggja ára járntöku. Blóðgjafir hækkuðu blóðrauða tímabundið en járngjafir í æð höfðu engin áhrif. Beinmergsrannsókn greindi arfgengt járnkímfrumublóðleysi. Pýridoxín leiðrétti blóðleysið en maðurinn þurfti á endurteknum aftöppunum að halda vegna mikillar járnofhleðslu. Nú tekur hann pýridoxín, er einkennalaus og með eðlilegan blóðhag

Differential diagnosis of iron deficiency

Iron deficiency is considered to be the commonest hematological pathology in humans. Thus, the essential steps in an adequate approach of iron deficiency include: the proper identification of its causes and the differentiation between iron deficiency and other conditions. This article briefly describes other conditions that may present with microcytic anemia such as thalassemia, anemia of chronic diseases, sideroblastic anemia and lead intoxication. These diseases should be considered during the investigation of iron deficiency anemia.A deficiência de ferro é considerada a patologia hematológica mais prevalente no homem. Assim, é fundamental a adequada identificação de suas causas, bem como a diferenciação com outras patologias distintas para adequada abordagem da deficiência de ferro. Neste artigo são brevemente descritas outras condições que podem cursar com anemia microcítica, tais como: talassemias, anemia de doença crônica, anemia sideroblástica e envenenamento por chumbo, patologias estas que devem ser afastadas durante investigação de anemia ferropriva.Universidade Federal de São Paulo (UNIFESP)UNIFESP/EpmUNIFESP/EpmSciEL

The Eye on Mitochondrial Disorders.

Ophthalmologic manifestations of mitochondrial disorders are frequently neglected or overlooked because they are often not regarded as part of the phenotype. This review aims at summarizing and discussing the etiology, pathogenesis, diagnosis, and treatment of ophthalmologic manifestations of mitochondrial disorders. Review of publications about ophthalmologic involvement in mitochondrial disorders by search of Medline applying appropriate search terms. The eye is frequently affected by syndromic as well as nonsyndromic mitochondrial disorders. Primary and secondary ophthalmologic manifestations can be differentiated. The most frequent ophthalmologic manifestations of mitochondrial disorders include ptosis, progressive external ophthalmoplegia, optic atrophy, retinopathy, and cataract. More rarely occurring are nystagmus and abnormalities of the cornea, ciliary body, intraocular pressure, the choroidea, or the brain secondarily affecting the eyes. It is important to recognize and diagnose ophthalmologic manifestations of mitochondrial disorders as early as possible because most are accessible to symptomatic treatment with partial or complete short-term or long-term beneficial effect. Ophthalmologic manifestations of mitochondrial disorders need to be appropriately diagnosed to initiate the most effective management and guarantee optimal outcome

Iron–sulfur clusters: from metals through mitochondria biogenesis to disease

Iron–sulfur clusters are ubiquitous inorganic co-factors that contribute to a wide range of cell pathways including the maintenance of DNA integrity, regulation of gene expression and protein translation, energy production, and antiviral response. Specifically, the iron–sulfur cluster biogenesis pathways include several proteins dedicated to the maturation of apoproteins in different cell compartments. Given the complexity of the biogenesis process itself, the iron–sulfur research area constitutes a very challenging and interesting field with still many unaddressed questions. Mutations or malfunctions affecting the iron–sulfur biogenesis machinery have been linked with an increasing amount of disorders such as Friedreich’s ataxia and various cardiomyopathies. This review aims to recap the recent discoveries both in the yeast and human iron–sulfur cluster arena, covering recent discoveries from chemistry to disease

Clinical and genetic aspects of defects in the mitochondrial iron-sulfur cluster synthesis pathway

Iron-sulfur clusters are evolutionarily conserved biological structures which play an important role as cofactor for multiple enzymes in eukaryotic cells. The biosynthesis pathways of the iron-sulfur clusters are located in the mitochondria and in the cytosol. The mitochondrial iron-sulfur cluster biosynthesis pathway (ISC) can be divided into at least twenty enzymatic steps. Since the description of frataxin deficiency as the cause of Friedreich's ataxia, multiple other deficiencies in ISC biosynthesis pathway have been reported. In this paper, an overview is given of the clinical, biochemical and genetic aspects reported in humans affected by a defect in iron-sulfur cluster biosynthesis

Survey of Human Mitochondrial Diseases Using New Genomic/Proteomic Tools

BACKGROUND. We have constructed Bayesian prior-based, amino-acid sequence profiles for the complete yeast mitochondrial proteome and used them to develop methods for identifying and characterizing the context of protein mutations that give rise to human mitochondrial diseases. (Bayesian priors are conditional probabilities that allow the estimation of the likelihood of an event - such as an amino-acid substitution - on the basis of prior occurrences of similar events.) Because these profiles can assemble sets of taxonomically very diverse homologs, they enable identification of the structurally and/or functionally most critical sites in the proteins on the basis of the degree of sequence conservation. These profiles can also find distant homologs with determined three-dimensional structures that aid in the interpretation of effects of missense mutations. RESULTS. This survey reports such an analysis for 15 missense mutations one insertion and three deletions involved in Leber's hereditary optic neuropathy, Leigh syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Mohr-Tranebjaerg syndrome, iron-storage disorders related to Friedreich's ataxia, and hereditary spastic paraplegia. We present structural correlations for seven of the mutations. CONCLUSIONS. Of the 19 mutations analyzed, 14 involved changes in very highly conserved parts of the affected proteins. Five out of seven structural correlations provided reasonable explanations for the malfunctions. As additional genetic and structural data become available, this methodology can be extended. It has the potential for assisting in identifying new disease-related genes. Furthermore, profiles with structural homologs can generate mechanistic hypotheses concerning the underlying biochemical processes - and why they break down as a result of the mutations.United States Department of Energy (DE-FG02-98ER62558); National Science Foundation (DBI-9807993

Case of the month

A 46 year old white male was admitted from the emergency department with severe pain in his legs, feet and hands, which began two days prior to admission. He described the bilateral pain as shooting and burning in nature; he was writhing in pain and rated its severity as 10/10. He denied trauma, current fever, chills or a history of back pain or arthritis

Interpreting iron studies

No abstract available

La Traducció genètica mitocondrial i malalties associades

En humans, com en la majoria d'organismes eucariotes, la síntesi proteica té lloc simultàniament al citoplasma i en orgànuls que posseeixen un genoma propi. Els mitocondris requereixen una maquinària traduccional pròpia per sintetitzar els tretze polipèptids, codificats al genoma mitocondrial, que formen part dels complexos de la cadena respiratòria i la fosforilació oxidativa responsables de proporcionar energia a la cèl·lula. Els elements que componen aquesta maquinària es troben codificats tant al genoma mitocondrial com al nuclear i participen de manera coordinada en la traducció genètica. Mutacions en els gens que codifiquen aquests factors de l'aparell de traducció genètica mitocondrial desencadenen un ampli ventall de malalties greus en humans, caracteritzades per símptomes heterogenis que en dificulten el diagnòstic i tractament. Hi ha malalties mitocondrials humanes causades per mutacions en el DNA mitocondrial que afecten específicament els tRNA i rRNA i, a més, s'han descrit mutacions en proteïnes mitocondrials codificades en el genoma nuclear, entre les quals es troben mutacions en factors de traducció, enzims de processament i modificació dels tRNA, proteïnes mitoribosòmiques i aminoacil-tRNA-sintetases mitocondrials. La complexitat de les malalties mitocondrials, la varietat de símptomes que causen i la dificultat de manipular genèticament el DNA mitocondrial compliquen la recerca relacionada amb aquestes malalties i justifiquen la generació de models animals que permetin caracteritzar-les i desenvolupar noves estratègies terapèutiques.In humans, as in the majority of eukaryotic organisms, protein synthesis occurs simultaneously in the cytoplasm and in those organelles that possess their own genome. Mitochondria require its own translational machinery in order to synthesize the 13 polypeptides, encoded in the mitochondrial genome, which are part of the respiratory chain and the oxidative phosphorylation complexes, responsible for supplying energy to the cell. The elements that compose this machinery are encoded both in the mitochondrial and the nuclear genome, and participate in gene translation in a coordinate manner. Mutations in genes that code for these factors of the gene translation apparatus trigger a wide range of severe pathologies in humans, characterized by heterogeneous symptoms that difficult their diagnostic and treatment. There exist human mitochondrial diseases caused by mutations in the mitochondrial DNA which specifically affect tRNA and rRNA and, additionally, mutations in nuclear encoded mitochondrial proteins have been described, among which are mutations in translation factors, enzymes involved in tRNA processing and modification, mitoribosomal proteins, and aminoacyl-tRNA synthetases. The complexity of mitochondrial pathologies, the variety of symptoms they cause, and the difficulty to manipulate mitochondrial DNA complicate the research related to these diseases and justify the generation of animal models that allow their characterization and the development of new therapeutic strategies