RESUMO
OBJECTIVE: The effects of iron deficiency on the prognosis of idiopathic sudden sensorineural hearing loss are unclear. This study aimed to investigate the association between serum iron levels and idiopathic sudden sensorineural hearing loss prognosis and its usefulness as an independent prognostic marker for idiopathic sudden sensorineural hearing loss. METHODS: The audiological and haematological data, including hearing recovery and serum iron levels, of 103 patients with idiopathic sudden sensorineural hearing loss evaluated between 2015 and 2018 were retrospectively analysed. RESULTS: The overall complete recovery rate was 16.5 per cent. Initial higher hearing threshold was associated with poor idiopathic sudden sensorineural hearing loss prognosis. Serum iron levels were significantly higher in the complete recovery group than in the non-complete recovery group (p < 0.05). CONCLUSION: The possibility of complete recovery from idiopathic sudden sensorineural hearing loss was significantly lower with lower serum iron levels, suggesting that the serum iron level might be a novel prognostic marker for idiopathic sudden sensorineural hearing loss.
Assuntos
Perda Auditiva Neurossensorial/sangue , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Súbita/sangue , Perda Auditiva Súbita/complicações , Deficiências de Ferro , Distúrbios do Metabolismo do Ferro/sangue , Distúrbios do Metabolismo do Ferro/complicações , Ferro/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosAssuntos
Distúrbios do Metabolismo do Ferro , Doenças Neurodegenerativas , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Ceruloplasmina/deficiência , Ceruloplasmina/genética , Ceruloplasmina/metabolismo , Humanos , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/genética , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/genética , Convulsões/genéticaAssuntos
Anemia Ferropriva/complicações , Catarata/congênito , Compostos Ferrosos/uso terapêutico , Hematínicos/uso terapêutico , Distúrbios do Metabolismo do Ferro/congênito , Administração Oral , Adulto , Anemia Ferropriva/tratamento farmacológico , Catarata/complicações , Catarata/tratamento farmacológico , China , Feminino , Compostos Ferrosos/administração & dosagem , Hematínicos/administração & dosagem , Humanos , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/tratamento farmacológico , LinhagemRESUMO
Several patients with beta-propeller protein-associated neurodegeneration (BPAN)/static encephalopathy with neurodegeneration in adulthood have been reported to present Rett syndrome (RTT)-like features. This report presents an individual with BPAN showing clinical features of RTT. Psychomotor delay and epilepsy onset were noted at 1 year, and regression began at 4 years. Screening of the methyl-CpG binding protein 2 (MECP2) did not show variants. At 22 years, basal ganglia iron deposits were found on magnetic resonance imaging (MRI), and the WD-domain repeat 45 gene (WDR45) variant was identified. Review of the literature showed that BPAN with RTT-like features is associated with more epileptic seizures and less deceleration of head growth, breathing irregularities, and cold extremities than classic RTT with MECP2 variants. These clinical presentations may provide clues for differentiating between these two disorders. However, both WDR45 and MECP2 should be screened in patients presenting a clinical picture of RTT without specific MRI findings of BPAN.
Assuntos
Encefalopatias/genética , Proteínas de Transporte/genética , Proteína 2 de Ligação a Metil-CpG/genética , Síndrome de Rett/genética , Adolescente , Adulto , Gânglios da Base/metabolismo , Gânglios da Base/patologia , Encefalopatias/complicações , Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Criança , Pré-Escolar , Epilepsia Parcial Complexa/complicações , Epilepsia Parcial Complexa/diagnóstico por imagem , Epilepsia Parcial Complexa/genética , Epilepsia Parcial Complexa/patologia , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Ferro , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/diagnóstico por imagem , Distúrbios do Metabolismo do Ferro/genética , Distúrbios do Metabolismo do Ferro/patologia , Imageamento por Ressonância Magnética , Síndrome de Rett/complicações , Síndrome de Rett/diagnóstico por imagem , Síndrome de Rett/patologia , Adulto JovemAssuntos
Ceruloplasmina/análise , Ceruloplasmina/deficiência , Diabetes Mellitus Tipo 1/complicações , Distúrbios do Metabolismo do Ferro/diagnóstico , Doenças Neurodegenerativas/diagnóstico , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Terapia por Quelação , Disfunção Cognitiva/etiologia , Diagnóstico Diferencial , Feminino , Ferritinas/sangue , Humanos , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/terapia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/terapia , Inconsciência/etiologiaRESUMO
INTRODUCTION: In mitochondrial membrane protein-associated neurodegeneration (MPAN), a subtype of neurodegeneration with brain iron accumulation (NBIA), patients suffer from optic nerve atrophy and dementia, which are also typical for another group of diseases, the mitochondrial diseases (MD). Around 30% of patients with MD have heart disease, commonly cardiomyopathy and arrhythmias, and 10% experience a major adverse cardiovascular event. The aim of this study was to assess cardiac involvement in MPAN. METHODS: Thirteen patients with MPAN were evaluated after written informed consent. All patients had echocardiography and 12 patients had 24-h Holter electrocardiogram (ECG) monitoring using 3-channel digital recorders. RESULTS: Echocardiography revealed normal values for the dimensions of all heart chambers. The systolic function of the left ventricle was normal in all cases. Right ventricle systolic impairment was found in three patients. 24-hour Holter ECG revealed predominant resting tachycardia during daytime with no physiological slowing of heart rate during sleep in seven cases. No significant arrhythmias were found. In nine patients, selected heart rate variability (HRV) parameters were lower than reference values. CONCLUSION: Cardiomyopathy, typical of MD, was not found in patients with MPAN. There were no significant arrhythmias, but disturbances in the circadian rhythm of the heart rate were observed in most cases. The decrease in HRV may reflect an early sign of autonomic dysfunction. A standard cardiac work-up is recommended for patients with MPAN to assess if additional treatment is needed.
Assuntos
Cardiopatias/etiologia , Distúrbios do Metabolismo do Ferro/complicações , Doenças Mitocondriais/complicações , Proteínas Mitocondriais/genética , Distrofias Neuroaxonais/complicações , Doenças Neurodegenerativas/complicações , Adolescente , Adulto , Eletrocardiografia , Feminino , Cardiopatias/diagnóstico , Humanos , Distúrbios do Metabolismo do Ferro/diagnóstico , Distúrbios do Metabolismo do Ferro/genética , Masculino , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/genética , Distrofias Neuroaxonais/diagnóstico , Distrofias Neuroaxonais/genética , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/genética , Adulto JovemRESUMO
Aceruloplasminemia is a rare iron-overload disease that should be better known by physicians. It is an autosomal recessive disorder due to mutations in ceruloplasmin gene causing systemic iron overload, including cerebral and liver parenchyma. The impairment of ferroxidase ceruloplasmin activity leads to intracellular iron retention leading aceruloplasminemia symptoms. Neurologic manifestations include cognitive impairment, ataxia, extrapyramidal syndrome, abnormal movements, and psychiatric-like syndromes. Physicians should search for aceruloplasminemia in several situations with high ferritin levels: microcytic anaemia, diabetes mellitus, neurological and psychiatric disorders. Diagnosis approach is based on the study of transferrin saturation and hepatic iron content evaluated by magnetic resonance imaging of the liver. Ceruloplasmin dosage is required in case of low transferrin saturation and high hepatic iron content and genetic testing is mandatory in case of serum ceruloplasmin defect. Neurological manifestations occur in the sixties decade and leads to disability. Iron chelators are widely used. Despite their efficacy on systemic and cerebral iron overload, iron chelators tolerance is poor. Early initiation of iron chelation therapy might prevent or slowdown neurodegeneration, highlighting the need for an early diagnosis but their clinical efficacy remains uncertain.
Assuntos
Ceruloplasmina/deficiência , Distúrbios do Metabolismo do Ferro/diagnóstico , Doenças Neurodegenerativas/diagnóstico , Ceruloplasmina/genética , Ceruloplasmina/metabolismo , Diagnóstico Diferencial , Humanos , Ferro/metabolismo , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/genética , Distúrbios do Metabolismo do Ferro/terapia , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/patologia , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/terapia , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/etiologia , Transtornos Parkinsonianos/metabolismo , Doenças RarasRESUMO
BACKGROUND: Mutations in the X-linked gene WDR45 cause neurodegeneration with brain iron accumulation type 5. Global developmental delay occurs at an early age with slow progression to dystonia, parkinsonism, and dementia due to progressive iron accumulation in the brain. METHODS: We present 17 new cases and reviewed 106 reported cases of neurodegeneration with brain iron accumulation type 5. Detailed information related to developmental history and key time to event measures was collected. RESULTS: Within this cohort, there were 19 males. Most individuals were molecularly diagnosed by whole-exome testing. Overall 10 novel variants were identified across 11 subjects. All individuals were affected by developmental delay, most prominently in verbal skills. Most individuals experienced a decline in motor and cognitive skills. Although most individuals were affected by seizures, the spectrum ranged from provoked seizures to intractable epilepsy. The imaging findings varied as well, often evolving over time. The classic iron accumulation in the globus pallidus and substantia nigra was noted in half of our cohort and was associated with older age of image acquisition, whereas myelination abnormalities were associated with younger age. CONCLUSIONS: WDR45 mutations lead to a progressive and evolving disorder whose diagnosis is often delayed. Developmental delay and seizures predominate in early childhood, followed by a progressive decline of neurological function. There is variable expressivity in the clinical phenotypes of individuals with WDR45 mutations, suggesting that this gene should be considered in the diagnostic evaluation of children with myelination abnormalities, iron deposition, developmental delay, and epilepsy depending on the age at evaluation.
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Proteínas de Transporte/genética , Doenças Desmielinizantes , Deficiências do Desenvolvimento , Epilepsia , Distúrbios do Metabolismo do Ferro , Distrofias Neuroaxonais , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/fisiopatologia , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/fisiopatologia , Epilepsia/diagnóstico , Epilepsia/etiologia , Epilepsia/genética , Epilepsia/fisiopatologia , Feminino , Humanos , Lactente , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/diagnóstico , Distúrbios do Metabolismo do Ferro/genética , Distúrbios do Metabolismo do Ferro/fisiopatologia , Masculino , Pessoa de Meia-Idade , Distrofias Neuroaxonais/complicações , Distrofias Neuroaxonais/diagnóstico , Distrofias Neuroaxonais/genética , Distrofias Neuroaxonais/fisiopatologia , Fenótipo , Sequenciamento do Exoma , Adulto JovemRESUMO
The enzyme heme oxygenase-1 (HO-1), encoded by the HMOX1 gene, mediates heme catabolism by cleaving free heme. We have previously revealed the importance of HO-1 in pregnancy. Here, we determined the impact of maternal or paternal HO-1 deficiency on fetal growth and placental parameters throughout gestation. We mated Hmox1-sufficient (WT), partial (HET)-, or total (KO)-deficient BALB/c female mice with Hmox1-WT or -KO BALB/c males and performed ultrasound analysis to monitor placental and fetal growth. Doppler measurements were used to determine maternal blood flow parameters. Offspring weights and feto-placental indices (FPI) were also determined. We found a significantly increased number of underdeveloped fetuses at gd10 in HET females that were mated with WT males compared with WT × WT pairings. At the same gestational age, underdeveloped placentas could be detected in HET females mated with KO males. Many fetuses from the KO × KO combination died in utero between gd12 and gd14. At gd14, abnormal placental parameters were found in surviving fetuses, which had significant reduced weights. Moreover, only 3.11% female and 5.33% male KO pups resulted from 10 HET × HET breeding pairs over 1 year. Our results show that HO-1 from both maternal and paternal origins is important for proper placental and fetal growth. Placental growth restriction and occurrence of abortions in mice that were partially or totally deficient in HO-1 were recorded in vivo from gd10 onwards. Future studies will focus on elucidating the cellular and molecular mechanisms behind these observations.
Assuntos
Anemia Hemolítica/complicações , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/enzimologia , Idade Gestacional , Transtornos do Crescimento/complicações , Heme Oxigenase-1/deficiência , Distúrbios do Metabolismo do Ferro/complicações , Ultrassonografia Pré-Natal , Anemia Hemolítica/genética , Animais , Cruzamentos Genéticos , Modelos Animais de Doenças , Feminino , Morte Fetal , Desenvolvimento Fetal/genética , Transtornos do Crescimento/genética , Heme Oxigenase-1/genética , Distúrbios do Metabolismo do Ferro/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Placenta/fisiopatologia , GravidezRESUMO
BACKGROUND: Aceruloplasminaemia is a very rare autosomal recessive disorder caused by a mutation in the ceruloplasmin gene, which is clinically manifested by damage to the nervous system and retinal degeneration. This classical clinical picture can be preceded by diabetes mellitus and microcytic anaemia, which are considered to be early manifestations of aceruloplasminaemia. CASE PRESENTATION: In our report, we describe the case of a patient with aceruloplasminaemia detected in an early stage (without clinical symptoms of damage to the nervous system) during the search for the cause of hepatopathy with very low values of serum ceruloplasmin. Molecular genetic examination of the CP gene for ceruloplasmin identified a new variant c.1664G > A (p.Gly555Glu) in the homozygous state, which has not been published in the literature or population frequency databases to date. Throughout the 21-month duration of chelatase treatment, the patient, who is 43 years old, continues to be without neurological and psychiatric symptomatology. We observed a decrease in the serum concentration of ferritin without a reduction in iron deposits in the brain on magnetic resonance imaging. CONCLUSION: Currently, there is no unequivocal recommendation of an effective treatment for aceruloplasminaemia. Early diagnosis is important in the neurologically asymptomatic stage.
Assuntos
Anemia/etiologia , Ceruloplasmina/deficiência , Ceruloplasmina/genética , Degeneração Hepatolenticular/diagnóstico , Distúrbios do Metabolismo do Ferro/diagnóstico , Mutação , Doenças Neurodegenerativas/diagnóstico , Obesidade/etiologia , Adulto , Anemia/diagnóstico , Doenças Assintomáticas , Diagnóstico Diferencial , Marcadores Genéticos , Humanos , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/genética , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/genética , Obesidade/diagnósticoRESUMO
The patient was a 64-year-old man presented with difficulty in walking, articulation, and swallowing, as well as cognitive impairment. He had refractory microcytic anemia and diabetes mellitus. His serum levels of iron, copper, and ceruloplasmin were low. Magnetic resonance imaging suggested iron deposition in the basal ganglia, thalami, cerebellar dentate nuclei, and cerebral and cerebellar cortices. He was diagnosed with aceruloplasminemia after a ceruloplasmin gene analysis. Iron chelation therapy with deferasirox improved his anemia and cerebellar symptoms, which included dysarthria and limb ataxia. The present study and previous reports indicate that cerebellar symptoms with aceruloplasminemia might respond to deferasirox in less than one year.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Ceruloplasmina/deficiência , Deferasirox/uso terapêutico , Quelantes de Ferro/uso terapêutico , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/tratamento farmacológico , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/tratamento farmacológico , Adulto , Ceruloplasmina/análise , Cobre/sangue , Feminino , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
AIM: Evaluation of pediatric palliative home care of families with children suffering from neurodegeneration with brain iron accumulation (NBIA) and their parents. MATERIAL AND METHODS: The children were treated at home by a multidisciplinary team. Densitometry was used to evaluate the condition of the skeletal system. Botulinum toxin was injected into the muscles in doses between 22 and 50 units/kg. The quality of palliative care was assessed on the basis of a specially designed questionnaire for parents. RESULTS: The observations were performed on a group of 9 patients with NBIA. On admission, the median age of patients was 9 years (7-14). The average time of palliative home care was 1569 days (34 days-17 years). The median age at death (6 patients) was 11 years (7-15). The botulinum toxin injections gave the following results: reduction of spasticity and dystonia, reduction of spine and chest deformation, relief of pain and suffering, facilitation of rehabilitation and nursing, prevention of permanent contractures, and reduction of excessive salivation. Bone mineral density and bone strength index were reduced. Two patients experienced pathological fracture of the femur. The body mass index at admission varied between 9.8 and 14.9. In 7 cases, introduction of a ketogenic diet resulted in the increase of body mass and height. The ketogenic diet did not worsen the neurological symptoms. The parents positively evaluated the quality of care. CONCLUSION: Palliative home care is the optimal form of treatment for children with NBIA.
Assuntos
Serviços de Assistência Domiciliar , Distúrbios do Metabolismo do Ferro/terapia , Distrofias Neuroaxonais/terapia , Fármacos Neuromusculares/farmacologia , Cuidados Paliativos/métodos , Adolescente , Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/etiologia , Toxinas Botulínicas/farmacologia , Criança , Distonia/tratamento farmacológico , Distonia/etiologia , Feminino , Humanos , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/tratamento farmacológico , Distúrbios do Metabolismo do Ferro/enfermagem , Masculino , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Dor Musculoesquelética/tratamento farmacológico , Dor Musculoesquelética/etiologia , Distrofias Neuroaxonais/complicações , Distrofias Neuroaxonais/tratamento farmacológico , Distrofias Neuroaxonais/enfermagemRESUMO
INTRODUCTION: Beta-propeller protein-associated neurodegeneration (BPAN) is a very rare, X-linked dominant (XLD) inherited member of the neurodegeneration with brain iron accumulation (NBIA) disease family. CASE REPORT: We present a female case of BPAN with infantile spasms in the first year, Rett-like symptomatology, focal epilepsy, and loss of motor skills in childhood. Menarche occurred at the age of 9, after precocious pubarche and puberty.Dystonia-parkinsonism as extrapyramidal sign at the age of 10 years resulted in radiological and genetic work-up. RESULTS: Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) measured 66/120 points in body part-related dystonia symptoms. Cerebrospinal fluid examination showed dopamine depletion.T2 and B0 sequences of the diffusion-weighted magnetic resonance imaging showed susceptibility artifacts with NBIA-typical hypointense globus pallidus (GP) and substantia nigra (SN). Next-generation sequencing revealed a BPAN-causing pathogenic variant in WDR45 (WD repeat-containing protein 45) gene (c.830 + 1G > A, XLD, heterozygous, de novo). Skewed X-inactivation was measured (2:98). CONCLUSIONS: Autophagy-related X-linked BPAN disease might still be underdiagnosed in female cases of infantile spasms.Skewed X-inactivation will have mainly influenced the uncommon, very early childhood neurodegenerative symptomatology in the present BPAN case. Oral levodopa substitution led to improvement in sleep disorder, hypersalivation, and swallowing.Reduced white matter and hypointense signals in SN and GP on susceptibility sequences in magnetic resonance imaging are characteristic radiological findings of advanced disease in NBIA. No BPAN-typical halo sign in T1-weighted scan at midbrain level was seen at the age of 11 years. NBIA panel is recommended for early diagnosis.
Assuntos
Distonia/etiologia , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/diagnóstico , Distrofias Neuroaxonais/complicações , Distrofias Neuroaxonais/diagnóstico , Transtornos Parkinsonianos/etiologia , Espasmos Infantis/etiologia , Criança , Feminino , Humanos , Lactente , Imageamento por Ressonância MagnéticaRESUMO
Iron is an essential element for cardiomyocyte viability and contractility. Systemic iron deficiency, even without anemia, is reflected by iron deficiency in cardiomyocytes. As in other cells, there is here a complex, local and autonomous regulation of iron metabolism, based on two molecular systems: the hepcidin/ferroportin/transferrin receptor-1 axis; and the iron regulatory proteins-1,2 system. These molecular pathways allow cardiomyocytes to react to changes in serum iron availability. In mice, dietary manipulations of serum iron availability or cardio-specific deletions and mutations of regulatory genes for intracellular iron metabolism have clarified some aspects of the causal relationship between cardiomyocyte iron deficiency and the development of severe heart failure, prevented by intravenous iron treatment even without the occurrence of iron deficiency (sideropenic) anemia. The deleterious effects of iron deficiency and hypoxia on gene expression of the main regulators of intracellular iron and oxygen metabolism and on cardiac function are very similar in heart failure and in chronic stable ischemic heart disease, and conjure towards cardiomyocyte injury. We here hypothesize that in non-anemic patients with stable ischemic heart disease a chronic or acute serum iron deficiency can amplify the chronic activation of the cardiomyocyte hypoxia-inducible factor-1α. As a consequence, cardiac adaptative responses to chronic hypoxia/ischemia are significantly impaired, and cardiac dysfunction exacerbated. We hypothesize that, in such patients, iron replacement through forced iron supplementation may replete cardiomyocyte iron deficiency and improve ischemic heart disease. This hypothesis requires further experimental studies, but also, and already now, specific clinical trials.
Assuntos
Insuficiência Cardíaca/etiologia , Deficiências de Ferro , Isquemia Miocárdica/etiologia , Animais , Doença Crônica , Modelos Animais de Doenças , Insuficiência Cardíaca/prevenção & controle , Humanos , Ferro/metabolismo , Ferro/uso terapêutico , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/tratamento farmacológico , Isquemia Miocárdica/prevenção & controle , Miocárdio/metabolismo , Miócitos Cardíacos/fisiologiaRESUMO
Hypoxia is common in many chronic lung diseases. Beyond pulmonary considerations, delivery of oxygen (O2) to the tissues and subsequent O2 utilisation is also determined by other factors including red blood cell mass and iron status; consequently, disruption to these mechanisms provides further physiological strains on an already stressed system. O2 availability influences ventilation, regulates pulmonary blood flow and impacts gene expression throughout the body. Deleterious effects of poor tissue oxygenation include decreased exercise tolerance, increased cardiac strain and pulmonary hypertension in addition to pathophysiological involvement of multiple other organs resulting in progressive frailty. Increasing inspired O2 is expensive, disliked by patients and does not normalise tissue oxygenation; thus, other strategies that improve O2 delivery and utilisation may provide novel therapeutic opportunities in patients with lung disease. In this review, we focus on the rationale and possibilities for doing this by increasing haemoglobin availability or improving iron regulation.
Assuntos
Anemia/complicações , Anemia/tratamento farmacológico , Hipóxia/tratamento farmacológico , Hipóxia/etiologia , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Doença Crônica , HumanosRESUMO
Hereditary aceruloplasminemia (HA), related to mutations in the ceruloplasmin (Cp) gene, leads to iron accumulation. Ceruloplasmin ferroxidase activity being considered essential for macrophage iron release, macrophage iron overload is expected, but it is not found in hepatic and splenic macrophages in humans. Our objective was to get a better understanding of the mechanisms leading to iron excess in HA. A clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated protein 9 (Cas9) knockout of the Cp gene was performed on Sprague-Dawley rats. We evaluated the iron status in plasma, the expression of iron metabolism genes, and the status of other metals whose interactions with iron are increasingly recognized. In Cp-/- rats, plasma ceruloplasmin and ferroxidase activity were absent, together with decreased iron concentration and transferrin saturation. Similarly as in humans, the hepatocytes were iron overloaded conversely to hepatic and splenic macrophages. Despite a relative hepcidin deficiency in Cp-/- rats and the loss of ferroxidase activity, potentially expected to limit the interaction of iron with transferrin, no increase of plasma non-transferrin-bound iron level was found. Copper was decreased in the spleen, whereas manganese was increased in the plasma. These data suggest that the reported role of ceruloplasmin cannot fully explain the iron hepatosplenic phenotype in HA, encouraging the search for additional mechanisms.-Kenawi, M., Rouger, E., Island, M.-L., Leroyer, P., Robin, F., Remy, S., Tesson, L., Anegon, I., Nay, K., Derbré, F., Brissot, P., Ropert, M., Cavey, T., Loréal, O. Ceruloplasmin deficiency does not induce macrophagic iron overload: lessons from a new rat model of hereditary aceruloplasminemia.
Assuntos
Ceruloplasmina/deficiência , Modelos Animais de Doenças , Distúrbios do Metabolismo do Ferro/complicações , Sobrecarga de Ferro/patologia , Ferro/metabolismo , Macrófagos/patologia , Doenças Neurodegenerativas/complicações , Animais , Sequência de Bases , Sistemas CRISPR-Cas , Ceruloplasmina/antagonistas & inibidores , Ceruloplasmina/genética , Feminino , Ferro/análise , Distúrbios do Metabolismo do Ferro/genética , Distúrbios do Metabolismo do Ferro/patologia , Sobrecarga de Ferro/etiologia , Fígado/metabolismo , Fígado/patologia , Macrófagos/metabolismo , Masculino , Mutação , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Ratos , Ratos Sprague-Dawley , Homologia de Sequência , Baço/metabolismo , Baço/patologiaRESUMO
Background: Specific phenomenology and pattern of involvement in movement disorders point toward a probable clinical diagnosis. For example, forehead chorea usually suggests Huntington's disease; feeding dystonia suggests neuroacanthocytosis and risus sardonicus is commonly seen in Wilson's disease. Dystonic opisthotonus has been described as a characteristic feature of neurodegeneration with brain iron accumulation (NBIA) related to PANK2 and PLA2G6 mutations. Case report: We describe two additional patients in their 30s with severe extensor truncal dystonia causing opisthotonic posturing in whom evaluation revealed the diagnosis of NBIA confirmed by genetic testing. Discussion: Dystonic opisthotonus may be more common in NBIA than it is reported and its presence especially in a young patient should alert the neurologists to a possibility of probable NBIA.
Assuntos
Distonia/etiologia , Distúrbios do Metabolismo do Ferro/complicações , Distrofias Neuroaxonais/complicações , Postura/fisiologia , Adulto , Distonia/fisiopatologia , Humanos , Distúrbios do Metabolismo do Ferro/diagnóstico , Distúrbios do Metabolismo do Ferro/genética , Masculino , Músculo Esquelético/fisiopatologia , Distrofias Neuroaxonais/diagnóstico , Distrofias Neuroaxonais/genética , Tronco/fisiopatologiaRESUMO
Hyperferritinemia, observed in inflammation, iron overload as well as in combination of both, is found in â¼30% of nonalcoholic fatty liver disease (NAFLD) patients. The authors summarized the evidence regarding the potential cause of hyperferritinemia in NAFLD, as this may affect the indicated therapy. A systematic literature search was conducted in EMBASE, PubMed, MEDLINE, and the Cochrane library. In the majority of NAFLD patients, hyperferritinemia is due to inflammation without hepatic iron overload. In a smaller group, a dysmetabolic iron overload syndrome (DIOS) is found, showing hyperferritinemia in combination with mild iron accumulation in the reticuloendothelial cells. The smallest group consists of NAFLD patients with hemochromatosis. Phlebotomy is only effective with hepatocellular iron overload and should not be the treatment when hyperferritinemia is related to inflammation, whether or not combined with DIOS. Treatment with lifestyle changes is to date probably the more effective way until new medication is becoming available.
Assuntos
Inflamação/complicações , Distúrbios do Metabolismo do Ferro/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Exercício Físico , Proteína da Hemocromatose/genética , Hepatócitos/metabolismo , Homeostase , Humanos , Distúrbios do Metabolismo do Ferro/terapia , Mutação , FlebotomiaRESUMO
AIMS: The aim of this study was to assess the burden of heart failure (HF) patients with/without iron deficiency/iron deficiency anaemia (ID/A) from the health insurance perspective. METHODS AND RESULTS: We conducted a retrospective claims database analysis using the Institut für angewandte Gesundheitsforschung Berlin research database. The study period spanned from 1 January 2012 to 31 December 2014. HF patients were identified by International Statistical Classification of Diseases and Related Health Problems, 10th revision, German Modification codes (I50.-, I50.0-, I50.00, I50.01, I50.1-, I50.11, I50.12, I50.13, I50.14, I50.19, and I50.9). HF patients were stratified into HF patients without ID/A and HF patients with ID/A (D50.-, D50.0, D50.8, D50.9, and E61.1). HF patients with ID/A were stratified into three subgroups: no iron treatment, oral iron treatment, and intravenous iron treatment. A matching approach was applied to compare outcomes for HF patients without ID/A vs. HF patient with untreated incident ID/A without iron treatment and for HF patients receiving no iron treatment vs. oral iron treatment vs. intravenous iron treatment. Matching parameters included exact age, sex, and New York Heart Association functional class. An optimization algorithm was used to balance total health care costs in the baseline period for the potential matched pairs without sample size reduction. In total, 172 394 (4537.4 per 100 000) HF patients were identified in the Institut für angewandte Gesundheitsforschung Berlin research database in 2013. Of these, 11.1% (19 070; 501.9 per 100 000) were diagnosed with ID/A and/or had a prescription for iron medication in 2013. The mean age of HF patients was 77.0 years (±12.0 years). Women were more frequently diagnosed with HF (54.6%). HF patients with untreated incident ID/A (1.77%) had a significantly higher all-cause mortality than HF patients without ID/A (33.1% vs. 24.1%, P < 0.01). The analysis of health care utilization revealed significant differences in the rate of all-cause hospitalization (72.9% vs. 50.5%, P < 0.01). The annual health care costs for HF patients with untreated incident ID/A amounted to 17 347 with incremental costs of 849 (P < 0.01) attributed to ID/A. CONCLUSIONS: Heart failure is associated with a major burden for patients and the health care system in terms of health care resource utilization, costs, and mortality. Our findings suggest that there is an unmet need for treating more HF patients with ID/A with iron medication.