Non-hereditary Diseases Research Articles

MiR-222-3p suppresses C2C12 myoblast proliferation and differentiation via the inhibition of IRS-1/PI3K/Akt pathway.

Numerous studies have revealed the profound impact of microRNAs on regulating skeletal muscle development and regeneration. However, the biological function and regulation mechanism of miR-222-3p in skeletal muscle remains largely unknown. In this study, miR-222-3p was found to be abundantly expressed in the impaired skeletal muscles, indicating that it might have function in the development and regeneration process of the skeletal muscle. MiR-222-3p overexpression impeded C2C12 myoblast proliferation and myogenic differentiation, whereas inhibition of miR-222-3p got the opposite results. The dual-luciferase reporter assay showed that insulin receptor substrate-1 (IRS-1) was the target gene of miR-222-3p. We next found that knockdown of IRS-1 could obviously suppress C2C12 myoblast proliferation and differentiation. Additionally, miR-222-3p-induced repression of myoblast proliferation and differentiation was verified to be associated with a decrease in phosphoinositide 3-kinase (PI3K)-Akt signaling. Overall, we demonstrated that miR-222-3p inhibited C2C12 cells myogenesis via IRS-1/PI3K/Akt pathway. Therefore, miR-222-3p may be used as a therapeutic target for alleviating muscle loss caused by inherited and nonhereditary diseases.

The Applications of the CRISPR/Cas9 Gene-Editing System in Treating Human Diseases

In the early 2010s, scientists realized that CRISPR/Cas9, a bacterial immune defense system against viruses that involves the CRISPR-associated protein #9 (Cas9) endonuclease enzyme, single-guide RNAs (sgRNAs), and PAM recognition, could be used to intentionally manipulate genes, essentially changing gene expression and regulation in such a way that would allow for a customized genome. Since then, CRISPR technology has revolutionized medical research and the biotechnology industry, and its newfound capabilities have scientists asking if CRISPR can be used to modify genes in such a way that would cure or treat certain harmful or life-threatening diseases. There have been CRISPR-based clinical studies done to treat β-thalassemia (TDT), sickle-cell disease (SCD), the human immunodeficiency virus (HIV), and several other genetic and non-hereditary diseases, but there is still a long way to go before CRISPR can become a widespread treatment for many more such diseases (Ebina et al., 2013; Esrick et al., 2021; Frangoul et al., 2021). Currently, researchers are looking to see if CRISPR is an accurate, specific, non-harmful, and effective treatment for these diseases, which means addressing and eliminating potential concerns about its safety and efficacy through extensive pre-clinical and clinical research, as well as overcoming moral and social obstacles. In this review, I will look at how the CRISPR/Cas9 gene-editing system can be applied in humans to prevent, cure, or treat these diseases, as well as what needs to be done before the CRISPR/Cas9 system can be made publicly available as a medical treatment for diseases.

Asymmetric form of pigmentary retinopathy (case study)

Unilateral pigmentary retinopathy (PR) is a rare, atypical form of hereditary retinal pathology. Different types of secondary retinopathy associated with various non-hereditary diseases, trauma or intoxication can imitate unilateral PR. Therefore, it is important to determine the cause of visual disorders and differentiate between unilateral and asymmetric PR. The article presents an example of using modern structural and functional diagnostic methods that helped diagnose the asymmetric form of the disease in a patient with suspected unilateral PR.

Non-infectious and non-hereditary diseases of the corneal epithelium

The corneal epithelium serves as a physical barrier and a refractive element. Therefore, diseases of the corneal epithelium can increase the risk for infection and causes vision loss. The corneal epithelium can be affected by a multitude of conditions, such as infections, hereditary diseases, depositions, trauma, autoimmune conditions, factitious disorders, and iatrogenic causes. Non-infectious and non-hereditary corneal epithelial diseases represent a collection of conditions with diverse etiologies and clinical presentations but similar patient symptoms. The differing therapeutic interventions for each condition make clinical distinction important. The clinical characteristics, disease course, pathophysiology and current treatments for non-infectious, non-hereditary corneal epithelial diseases are reviewed.

Therapeutic Strategies for Attenuation of Retinal Ganglion Cell Injury in Optic Neuropathies: Concepts in Translational Research and Therapeutic Implications.

Retinal ganglion cell (RGC) death is the central and irreversible endpoint of optic neuropathies. Current management of optic neuropathies and glaucoma focuses on intraocular pressure-lowering treatment which is insufficient. As such, patients are effectively condemned to irreversible visual impairment. This review summarizes experimental treatments targeting RGCs over the last decade. In particular, we examine the various treatment modalities and determine their viability and limitations in translation to clinical practice. Experimental RGC treatment can be divided into (1) cell replacement therapy, (2) neuroprotection, and (3) gene therapy. For cell replacement therapy, difficulties remain in successfully integrating transplanted RGCs from various sources into the complex neural network of the human retina. However, there is significant potential for achieving full visual restoration with this technique. Neuroprotective strategies, in the form of pharmacological agents, nutritional supplementation, and neurotrophic factors, are viable strategies with encouraging results from preliminary noncomparative interventional case series. It is important to note, however, that most published studies are focused on glaucoma, with few treating optic neuropathies of other etiologies. Gene therapy, through the use of viral vectors, has shown promising results in clinical trials, particularly for diseases with specific genetic mutations like Leber's hereditary optic neuropathy. This treatment technique can be further extended to nonhereditary diseases, through transfer of genes promoting cell survival and neuroprotection. Crucially though, for gene therapy, teratogenicity remains a significant issue in translation to clinical practice.

The modern concept of teaching genetics at a medical higher educational institution

Aim. To study and evaluate the peculiarities of teaching genetics in the system of higher medical education of Ukraine. Methods. Studying typical and working programs of educational disciplines of medical universities, analysis of their interconnections with the volume and depth of knowledge and achievements of genetics. Results. The worldwide rapid development of genetic technologies, that open up new possibilities for the diagnosis, treatment and prevention of many hereditary and non-hereditary diseases, requires the unification of the disparate efforts of scientists and practitioners. A significant role in solving this task should be played by higher medical school. Compact information about general genetics and the basics of anthropogenetics is received by medical students in the first year of study. This creates an appropriate basis for understanding the basic laws of the emergence of various forms of human pathologies, but does not ensure the assimilation of the genetic methodology of clinical disciplines and sections related to the organization of health protection and social medicine. Conclusions. An urgent need as of today is an inter-departmental and multi-level program on general genetics, human genetics, medical and clinical genetics, which would be compiled in accordance with the achievements of modern biology, medicine and genetics, and would penetrate all the stages of undergraduate and postgraduate education of doctors.
 Keywords: genetics, teaching in higher medical school.

Postaxial limb hypoplasia (PALH): the classification, clinical features, and related developmental biology.

Postaxial limb hypoplasia (PALH) is a group of nonhereditary diseases with congenital lower limb deficiency affecting the fibular ray, including fibular hemimelia, proximal femoral focal deficiency, and tarsal coalition. The etiology and the developmental biology of the anomaly are still not fully understood. Here, we review the previous classification systems, present the clinical features, and discuss the developmental biology of PALH.

Polymorphism of the clinical manifestations of progressive mitochondrial encephalomyopathy associated with POLG1 gene mutation

The common cause of mitochondrial diseases is mutations in the POLG1 gene encoding the catalytic subunit of DNA-polymerase gamma that is responsible for the replication and repair of mitochondrial DNA. Diseases associated with POLG1 gene defects are characterized by obvious clinical polymorphism and may resemble some mitochondrial syndromes and other hereditary and nonhereditary diseases, which gives rise to diagnostic difficulties. Another characteristic feature is that phenotypic manifestations are of diversity in various patients having the same mutation in the POLG1 gene. The paper describes mitochondrial encephalomyopathy, caused by homozygous mutation in the polymerase gamma (POLG1, p.L304R), with different clinical manifestations and a poor outcome in patients from two different families.

Anti-IL1ß-monoclonal antibody in two adult patients with PFAPA Syndrome - a single centre experience

Background The periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome belongs to the rare nonhereditary autoinflammatory diseases and normally onsetting in childhood, but despite of tonsillectomy persisting or newly occurring in adulthood. The exact pathogenesis is not clear, but to our understanding it is an acquired autoinflammatory disease due to an unregulated production of cytokines. The common treatment varies from NSAIDS, colchicine, corticosteroids up to blocking IL1receptor.

PD3-04 LESS POSTERIOR RETROPERITONEOSCOPIC ADRENALECTOMY: STEP-BY-STEP TECHNIQUE DESCRIPTION AND COMPARISON WITH 3-PORTS LATERAL RETROPERITONEAL APPROACH

INTRODUCTION AND OBJECTIVES: When a biochemically active adrenal mass is found surgery is usually recommended. While partial adrenalectomy is gaining popularity for small adrenal masses, it is not clear which patients will benefit from adrenal sparing to preserve adrenal function in case of contralateral adrenal pathology. We reviewed the available literature to evaluate the frequency of bilaterality of adrenal involvement with most common primary adrenal tumors and frequency of other pathologies potentially threatening the health of the adrenal gland. METHODS: We reviewed the PUBMED literature to evaluate the reported bilaterality of primary adrenal tumors including hereditary and nonhereditary pheochromocytomas (PHEOs), aldosterone producing adenomas (APAs), and cortisol producing adenomas and identified 25 articles describing the frequency of bilaterality of adrenalmasses.Wealso reviewed the literature to assess the etiologies of adrenal damage due to other pathological processes that may affect the adrenal gland in the lifespan of a patient and calculated the combined probability for adrenal damage. RESULTS: Table 1 reports the bilaterality of adrenal tumors in hereditary and non-hereditary diseases and demonstrates that adrenal tumors range in bilaterality between 4.25 e 80%. Hereditary PHEOs were bilateral in up to 80% of cases, while nonhereditary PHEOs were bilateral in up to 25%. APAs were bilateral in about 4% of cases, while only case reports reported bilaterality in cortisol producing tumors. Additionally, review of other processes such as infections, infiltrative etiologies, metastasis to adrenal, and others accounted for about 1% chance for the adrenal damage from all possible causes. CONCLUSIONS: Partial adrenalectomy is a valid option for patients with hereditary syndromes as there is an increased likelihood of disease in the contralateral gland. PHEOs followed by APAs appear to have the highest rate of bilateral involvement. Coupled with a possibility that an additional 1% of the population may have adrenals affected by various pathologic processes, partial adrenalectomy in patients with PHEO and APAs should be strongly considered. Percentage of bilaterality of adrenal tumors in hereditary syndromes and non-hereditary disease

PD3-03 RATIONALE FOR PARTIAL ADRENALECTOMY: REVIEW OF DANGERS TO ADRENAL GLAND

You have accessJournal of UrologyAdrenal1 Apr 2015PD3-03 RATIONALE FOR PARTIAL ADRENALECTOMY: REVIEW OF DANGERS TO ADRENAL GLAND Alosh Madala, Michael Daugherty, and Gennady Bratslavsky Alosh MadalaAlosh Madala More articles by this author , Michael DaughertyMichael Daugherty More articles by this author , and Gennady BratslavskyGennady Bratslavsky More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.290AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES When a biochemically active adrenal mass is found surgery is usually recommended. While partial adrenalectomy is gaining popularity for small adrenal masses, it is not clear which patients will benefit from adrenal sparing to preserve adrenal function in case of contralateral adrenal pathology. We reviewed the available literature to evaluate the frequency of bilaterality of adrenal involvement with most common primary adrenal tumors and frequency of other pathologies potentially threatening the health of the adrenal gland. METHODS We reviewed the PUBMED literature to evaluate the reported bilaterality of primary adrenal tumors including hereditary and non-hereditary pheochromocytomas (PHEOs), aldosterone producing adenomas (APAs), and cortisol producing adenomas and identified 25 articles describing the frequency of bilaterality of adrenal masses. We also reviewed the literature to assess the etiologies of adrenal damage due to other pathological processes that may affect the adrenal gland in the lifespan of a patient and calculated the combined probability for adrenal damage. RESULTS Table 1 reports the bilaterality of adrenal tumors in hereditary and non-hereditary diseases and demonstrates that adrenal tumors range in bilaterality between 4.25 – 80%. Hereditary PHEOs were bilateral in up to 80% of cases, while nonhereditary PHEOs were bilateral in up to 25%. APAs were bilateral in about 4% of cases, while only case reports reported bilaterality in cortisol producing tumors. Additionally, review of other processes such as infections, infiltrative etiologies, metastasis to adrenal, and others accounted for about 1% chance for the adrenal damage from all possible causes. CONCLUSIONS Partial adrenalectomy is a valid option for patients with hereditary syndromes as there is an increased likelihood of disease in the contralateral gland. PHEOs followed by APAs appear to have the highest rate of bilateral involvement. Coupled with a possibility that an additional 1% of the population may have adrenals affected by various pathologic processes, partial adrenalectomy in patients with PHEO and APAs should be strongly considered. Percentage of bilaterality of adrenal tumors in hereditary syndromes and non-hereditary disease Bilaterality of Adrenal Tumors % Incidentaloma 7.8 Pheochromocytomas Hereditary MEN Syndrome 35-80 VHL 40-60 Nonhereditary Pediatric 25 Adrenal Incidentaloma 10-15 Aldosterone Producing Adenoma 4.26 Cortisol Producing Adenoma Case reports only. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e82 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alosh Madala More articles by this author Michael Daugherty More articles by this author Gennady Bratslavsky More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Systematic drug repositioning for a wide range of diseases with integrative analyses of phenotypic and molecular data.

Drug repositioning, or the application of known drugs to new indications, is a challenging issue in pharmaceutical science. In this study, we developed a new computational method to predict unknown drug indications for systematic drug repositioning in a framework of supervised network inference. We defined a descriptor for each drug-disease pair based on the phenotypic features of drugs (e.g., medicinal effects and side effects) and various molecular features of diseases (e.g., disease-causing genes, diagnostic markers, disease-related pathways, and environmental factors) and constructed a statistical model to predict new drug-disease associations for a wide range of diseases in the International Classification of Diseases. Our results show that the proposed method outperforms previous methods in terms of accuracy and applicability, and its performance does not depend on drug chemical structure similarity. Finally, we performed a comprehensive prediction of a drug-disease association network consisting of 2349 drugs and 858 diseases and described biologically meaningful examples of newly predicted drug indications for several types of cancers and nonhereditary diseases.

Familial ainhum: a case report of multiple toe involvement in a father and son, staging of ainhum with insight into different types of constricting bands.

Ainhum, also known as dactylolysis spontanea, is a painful constriction of the base of the fifth toe, frequently followed by spontaneous amputation a few years later. The disease is often symmetrical on both the feet, but, occasionally, other toes are also affected and rarely the distal phalanx of the fifth finger. Pseudoainhum is a similar condition that occurs as a secondary event resulting from certain hereditary and nonhereditary diseases that lead to annular constriction of digits. We hereby present a case of familial ainhum in father and son with multiple toes affected, autoamputation, and more involvement of fourth toe than the fifth toe, which is a very rare finding.

Fasciculations in human hereditary disease.

Fasciculations are a manifestation of peripheral nerve hyperexcitability in addition to myokymia, neuromyotonia, cramps, or tetany. Fasciculations occur in hereditary and non-hereditary diseases. Among the hereditary diseases, fasciculations are most frequently reported in familial amyotrophic lateral sclerosis (FALS), and spinal muscular atrophy (SMA). Among the non-hereditary diseases, fasciculations occur most frequently in peripheral nerve hyperexcitability syndromes (Isaac's syndrome, voltage-gated potassium channelopathy, cramp fasciculation syndrome, Morvan syndrome). If the cause of fasciculations remains unknown, they are called benign. Systematically reviewing the literature about fasciculations in hereditary disease shows that fasciculations can be a phenotypic feature in bulbospinal muscular atrophy (BSMA), GM2-gangliosidosis, triple-A syndrome, or hereditary neuropathy. Additionally, fasciculations have been reported in familial amyloidosis, spinocerebellar ataxias, Huntington's disease, Rett syndrome, central nervous system disease due to L1-cell adhesion molecule (L1CAM) mutations, Fabry's disease, or Gerstmann-Sträussler disease. Rarely, fasciculations may be a phenotypic feature in patients with mitochondrial disorders or other myopathies. Fasciculations are part of the phenotype in much more genetic disorders than commonly assumed. Fasciculations not only occur in motor neuron disease, but also in hereditary neuropathy, spinocerebellar ataxia, GM2-gangliosidosis, Huntington's disease, Rett syndrome, Fabry's disease, Gerstmann-Sträussler disease, mitochondrial disorders, or muscular dystrophies.

A Potential New Therapeutic Approach for Friedreich Ataxia: Induction of Frataxin Expression With TALE Proteins

TALEs targeting a promoter sequence and fused with a transcription activation domain (TAD) may be used to specifically induce the expression of a gene as a potential treatment for haploinsufficiency. This potential therapeutic approach was applied to increase the expression of frataxin in fibroblasts of Friedreich ataxia (FRDA) patients. FRDA fibroblast cells were nucleofected with a pCR3.1 expression vector coding for TALEFrat#8 fused with VP64. A twofold increase of the frataxin mRNA (detected by quantitative reverse transcription-PCR (qRT-PCR)) associated with a similar increase of the mature form of the frataxin protein was observed. The frataxin mRNA and protein were also increased by this TALE in the fibroblasts of the YG8R mouse model. The addition of 5-aza-2′-deoxycytidine (5-Aza-dC) or of valproic acid (VPA) to the TALE treatment did not produce significant improvement. Other TADs (i.e., p65, TFAP2α, SRF, SP1, and MyoD) fused with the TALEFrat#8 gene did not produce a significant increase in the frataxin protein. Thus the TALEFrat#8-VP64 recombinant protein targeting the frataxin promoter could eventually be used to increase the frataxin expression and alleviate the FRDA symptoms.

Horse genomics and the Dorothy Russell Havemeyer Foundation

In 1995, the Dorothy Russell Havemeyer Foundation (DRHF) conducted the First International Equine Gene Mapping Workshop in Lexington, Kentucky. Scientists working on horses needed information about the equine genome to better perform their research. The scientific advances of the Human Genome Project, begun in 1990, were providing tools and information that made this goal attainable. The DRHF conducted a series of horse genome workshops between 1997 and 2009 in San Diego, USA; Uppsala, Sweden; Brisbane, Australia; Pretoria, South Africa; Dublin, Ireland; Lake Tahoe, USA; and Newmarket, UK. Over 200 scientists from 20 countries around the world participated in these workshops, sharing ideas and resources, collaborating and creating a common genomics framework. In 2006, the National Human Genome Research Institute (NHGRI) in the USA chose to sequence the horse as a consequence, in part, of both the work done by this community of scientists and their research interests going forward. As a result, the complete DNA sequence of the horse is available online (Wade et al. 2009) and has enabled powerful new research methods for equine science. This special issue of Animal Genetics was funded by the DRHF to underscore the importance of the genome to horse research. In this issue, scientists report research and discoveries made possible using the new genomic information. Indeed, the work includes gene discoveries and genetic characterization of horse breeds and sheds light on hereditary conditions that affect performance of horses. But the genome information is also useful to understand nonhereditary diseases and traits as well. Several reports in this issue address gene expression in connection with exercise and laminitis. Importantly, this is just the beginning. As scientists become more familiar with using genomic information for equine studies, we can anticipate more discoveries and the development of new diagnostic tests, therapeutic products and management approaches to improve the health and well-being of the horse. The impact of these studies and the availability of genome information for the horse will be significant at many levels. Good health is a high priority for horses. Owners and breeders train and select horses for a wide variety of characteristics including conformation, athleticism, temperament, intelligence, speed, stamina and coat colour. Poor health can undo years of work on part of the horse owner. Furthermore, the horse industry contributes significantly to economies around the world. Although we no longer depend on horses for power and transportation, horses continue to be an important agricultural product. A 2005 study in the United States suggested that the horse industry had a $102 billion (indirect) impact and provided employment (indirect and induced) to more than 1.4 million people (American Horse Council, 2005). The worldwide economic impact of the horse is obviously much larger. Use of the genome sequence in research will have far reaching effects on the health of horses and the health of the economy, worldwide. This should be remembered as a legacy from the Dorothy Russell Havemeyer Foundation.

Resumen de la evolución de las técnicas de citogenética y genética molecular para la identificación de las alteraciones genéticas del desarrollo embrionario

Spectacular progress has been made in the knowledge of human genetic material since the middle of the last century: the chromosomes have been characterised; the complete sequence of the genome has been identified. Also, all types of diseases hereditary and non-hereditary diseases (especially cancers) have been associated to changes in DNA structure and sequence. These developments have been accompanied by a great number of techniques, which have led to the investigation and characterisation of the human genetic load, and its application in clinical practice for the diagnosis of certain diseases. This has meant that, besides studies at molecular level for identifying a gene mutation, conventional cytology has extended to the detection of extremely small changes in the structure of the chromosome, giving rise to a new area of diagnosis called molecular cytogenetics. This includes various techniques that detect small changes, in decreasing order, from microdeletions and microduplications detectable by fluorescent probes (FISH), to genomic arrays and arrays based on compared genomic (CGH) which detect even smaller changes. However, due to their high resolution, arrays are capable of identifying variations in DNA, which in many cases its importance is still uncertain. This implies that even some of the most common techniques currently used, such as CGH, require a careful evaluation before offering a diagnosis.

Secreted bone morphogenetic protein antagonists of the Chordin family.

Chordin, Chordin-like 1, and Chordin-like 2 are secreted bone morphogenetic protein (BMP) antagonists with highly conserved Chordin-like cysteine-rich domains. Recently, Brorin and Brorin-like have been identified as new Chordin-like BMP antagonists. A Chordin ortholog, Short gastrulation, has been identified in Drosophila, a protostome, but not other orthologs. By contrast, Chordin, Chordin-like 1, and Chordin-like 2 have been identified in Ciona intestinalis, the closest living relatives of the vertebrates, but Brorin and Brorin-like have not. However, all these genes have been identified in most vertebrates. These results indicate that Chordin, Chordin-like 1, and Chordin-like 2 were generated early in the metazoan lineage. Later on, Brorin and Brorin-like were potentially generated by a genome duplication event in early vertebrate evolution. All four cysteine-rich domains of Chordin are essential for the regulation of its action. However, Chordin-like 1, Chordin-like 2, Brorin, and Brorin-like contain only two or three cysteine-rich domains. Although their mechanisms of action remain unclear, they might be distinct from that of Chordin. The expression profiles of these genes in mice and zebrafish indicate unique roles at embryonic and postnatal stages. Mutant/knockdown mouse and zebrafish phenotypes indicate roles in morphogenesis during gastrulation, dorsoventral axis formation, ear, pharyngeal, and neural development, and venous and arterial patterning. Aberrant Chordin expression might result in hereditary diseases and cancer. In addition, altered serum Chordin and Chordin-like 1 levels are also observed in non-hereditary diseases. Together, these results indicate pathophysiological roles.

Hereditary and non-hereditary microangiopathies in the young. An up-date

In recent years, a considerable number of new sporadic or hereditary small artery diseases of the brain have been detected which preferably occur in younger age, below 45 years. Cerebral microangiopathies constitute an appreciable portion of all strokes. In middle aged patients, hereditary cerebral small vessel diseases have to be separated from sporadic degenerative cerebral microangiopathy which is mainly due to a high vascular risk load. Features of the following disorders and details how to differentiate them, are reviewed here, namely CADASIL, MELAS, AD-RVLC, HEMID, CARASIL, PADMAL, FABRY, COL4A1-related cerebral small vessel diseases and a Portuguese type of autosomal dominant cerebral small vessel disease (SVDB). The symptomatic overlap of the cerebral microangiopathies include also other distinctive non-hereditary diseases like posterior (reversible) encephalopathy and Susac's syndrome which are also described. Some of the microangiopathies described here are not only seen in the young but also in the elderly. The precise diagnosis has direct therapeutic implications in several of these entities. Cerebral microangiopathies cause recurring strokes and diffuse white matter lesions leading to a broad spectrum of gait disturbances and in most of these disorders cognitive impairment or even vascular dementia in the long term. Often, they also involve the eye, the inner ear or the kidney. Several typical imaging findings from illustrative cases are presented. The order in which these diseases are presented here is not dictated by an inner logic principle, because a genetically or pathophysiologically based classification system of all these entities does not exist yet. Some entities are well established and not unusual, whereas others have only been described in a few cases in total.

Iron Overload Disorders: Treatment Options for Patients Refractory to or Intolerant of Phlebotomy

Iron overload disorders involve excess accumulation of iron in body tissues as a result of hereditary and nonhereditary diseases. If left untreated, tissue iron deposition can result in organ damage. Treatment options such as phlebotomy, chelating agents, and erythrocytapheresis can prevent complications and target organ damage. Although phlebotomy is the gold standard for iron overload treatment in the setting of hereditary hemochromatosis, this procedure is usually not feasible for other iron overload conditions, especially those associated with anemia. With the introduction of newer, oral chelating agents, more options are available for patients refractory to or intolerant of parenteral chelating agents.