遗传性血色病五例临床分析

目的探讨遗传性血色病的临床特点,评价铁生化指标、MRI、肝穿病理学检查在遗传性血色病诊断中的作用。方法5例患者,4男1女。先证者因不明原因肝硬化伴皮肤黏膜色素沉着来院确诊。通过对先证者的家系调查,进行临床、铁生化指标、胸腹部MRI、病理组织学和特殊染色的观察,确诊4例早期患者。结果该家系5例患者中3例出现皮肤黏膜色素沉着,1例肝硬化,未见糖尿病;5例患者血清铁均正常,其中3例血清铁蛋白异常;2例肝穿病理检查,其中1例肝铁过多沉积;而MRI显示每例患者至少有1个内脏器官的铁沉积,以肝脏铁沉积最为显著。结论遗传性血色病患者在我国较少见,临床特点不明显,诊断困难,尤其是遗传性血色病早期患者。家系调查结合MRI检测对遗传性血色病的早期诊断显得更为重要。     

非HFE相关遗传性血色病

遗传性血色病(HH)多为常染色体隐性遗传病,其特征是肠道铁吸收过多导致肝、胰、心及其它脏器铁过量沉积,引发肝硬化、内分泌疾病、心力衰竭、心律失常、关节病和皮肤色素沉着等临床表现.Ⅰ型HH最常见,由6号染色体HFE基因突变所致.非HFE相关HH是指无HFE致病性突变的几种表型相近但遗传学形式独特的HH,由于受累基因在铁代谢作用中的不同,较典型HH临床发病可能更早,表型表现度更严重.     

遗传性血色病1例报告

目的 探讨遗传性血色病的发病机制、临床表现,评价铁生化指标、肝穿病理学检查在遗传性血色病诊断中的作用.方法 回顾性分析1例遗传性血色病临床资料.结果 本病例男性,41岁,有乏力症状,皮肤有色素沉着;实验室检查示：血清铁蛋白、血糖、肝功异常;MRI示：肝脏体积增大,肝脏实质信号在T1W1/T2W1均匀减低,呈极低信号;予以铁络合剂治疗后诸证缓解,各项化验指标下降.结论 遗传性血色病患者在我国较少见,临床特点不明显,诊断困难,尤其是遗传性血色病早期患者,家系调查、MRI检测对遗传性血色病的早期诊断显得更为重要.     

遗传性血色病性肝硬化近展

遗传性血色病(ｈｅｒｅｄｉｔａｒｙｈｅｍｏｃｈｒｏｍａｔｏｓｉｓ,ＨＣＣ),又称原发性血色病,是纯合子在第6对染色体ＨＬＡ位点紧密连锁的常染色体隐性遗传病。由于先天性铁代谢障碍,体内有过多的铁沉积引起肝、胰、心、肾、皮肤等器官组织损伤和功能障碍。由此引起的肝硬化称血色病性肝硬化。一旦肝硬化发生,血色病的病死率则明显增高。ＨＣＣ临床上并非少见。据报告美国约有60～100万血色病者,另有2700万人是铁吸收增加而症状不明显的携带者,以白种人发病较高。国内对ＨＣＣ的发病率尚无确切统计数字,但全国各地均见病例报道。1发病机…     

SLC40 A1基因突变致遗传性血色病1例报告

正遗传性血色病(hereditary hemochromatosis, HH)是一种罕见的常染色体遗传病,北欧高加索人群发病率较高,其发病机制为铁代谢相关基因突变导致小肠对铁吸收过多,体内过量的铁进行性蓄积造成肝、肾、脑、胰腺等组织损伤,从而引起器官功能障碍导致肝硬化、糖尿病、心肌病、垂体损伤、睾丸萎缩、关节疾病和皮、肤色素沉着等~([1])。现将本院收治的1例HH患者的临床资料报道如下。     

转铁蛋白受体2基因突变相关血色病1例

遗传性血色病是一种铁代谢障碍性疾病,较为罕见。现报道1例转铁蛋白受体（TFR）2基因突变相关血色病患者,临床表现为皮肤色素沉着、糖尿病、肝硬化,血清铁蛋白（8 548.9 ng/ml）、转铁蛋白饱和度（116.77%）明显升高,肝活检示肝硬化,肝内铁沉积（重度Ⅳ级）,对其血液标本进行全外显子捕获和高通量测序,并经San...     

一个遗传性血色病家系的临床特点及其遗传基础初探

目的 探讨一个遗传性血色病家系的临床特点及初步查找该家系的遗传基础. 方法对该家系成员进行问诊、体检、实验室检查、多器官MRI检查、肝穿刺活组织检查(铁染色),绘制家系图谱.采集血样,对常见的遗传性血色病致病基因进行测序分析. 结果该家系成员中有7人存在铁过载,临床诊断为遗传性血色病.家系患者代代相传,无性别差异,外显率约46%.常见的SLC40A1和HFE基因突变位点在该家系成员中未发现. 结论该遗传性血色病家系患者以皮肤色素沉着、肝脾等脏器铁沉积最具特征,为常染色体显性遗传,但其遗传基础尚不明确.     

探讨Ⅳ型遗传性血色病肝脏hepcidin mRNA表达及意义

目的探讨Ⅳ型遗传性血色病肝脏hepcidin mRNA表达及临床意义。方法对一例遗传性血色病先证者的家系进行遗传学问询,病史采集,体格检查,实验室检查,MRI检查及肝脏组织病理学检查,运用实时荧光定量PCR法检测肝脏hepcidin mRNA表达,并进行遗传性血色病发病相关基因的基因筛查。结果该家系15人有7例经MRI证实存在不同程度实质脏器铁沉积,3例接受肝活检者中的2例肝脏组织普鲁士蓝染色证实铁沉积,实时荧光定量PCR法检测显示肝脏hepcidin mRNA表达上调,外周静脉血基因筛查发现2q32的SLC40A1六号外显子有一处碱基发生点突变,即T173C。结论1.本家系罹患Ⅳ型遗传性血色病,遗传学特征为常染色体显性遗传,SLC40A1六号外显子有一处点突变,但该突变与国际上先前报道的突变位点并不相符,说明该基因突变可能是新的突变类型;2.本家系肝脏hepcidin mRNA表达上调,提示血清hepcidin水平升高,说明可能存在hepcidin抵抗现象,使机体对hepcidin负性调节低反应,从而导致铁代谢紊乱出现铁沉积并出现脏器功能损害。     

遗传性肾小管疾病及其分子发病机制

肾小管上皮细胞膜上有一些特殊的离子通道和转运体,它们选择性地重吸收和排泌不同的离子进入尿液中,调节机体的容量、电解质浓度和酸碱平衡。肾小球滤过的水和电解质99%从肾小管重吸收。一些遗传性的肾小管疾病其分子发病机制就是编码这些离子通道或转运体的基因突变,致使相应的离子通道和转运体的结构和功能异常从而导致严重的代谢紊乱。虽然这些遗传性肾小管疾病并不常见,但深入了解这些疾病的分子基础,有助于我们了解肾小管的生理功能,肾脏维持水、盐、酸碱代谢平衡复杂的生理机制,及肾脏与其他系统(如内分泌系统中肾素、醛固酮轴)的相互…     

Hepcidin levels in hereditary hyperferritinemia: Insights into the iron-sensing mechanism in hepatocytes

AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the L-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 years.RESULTS:The serum hepcidin an...     

Pathophysiology of hereditary hemochromatosis

Hereditary hemochromatosis (HH) encompasses several inherited disorders of iron homeostasis characterized by increased gastrointestinal iron absorption and tissue iron deposition. The most common form of this disorder is HFE-related HH, nearly always caused by homozygosity for the C282Y mutation. A substantial proportion of C282Y homozygotes do not develop clinically significant iron overload, suggesting roles for environmental factors and modifier genes in determining the phenotype. Recent studies have demonstrated that the pathogenesis of nearly all forms of HH involves inappropriately decreased expression of the iron-regulatory hormone hepcidin. Hepcidin serves to decrease the export of iron from reticuloendothelial cells and absorptive enterocytes. Thus, HH patients demonstrate increased iron release from these cell types, elevated circulating iron, and iron deposition in vulnerable tissues. The mechanism by which HFE influences hepcidin expression is an area of current investigation and may offer insights into the phenotypic variability observed in persons with mutations in HFE.     

Management of hereditary hemochromatosis

Hereditary hemochromatosis is a common disorder of iron metabolism with a prevalence as high as 8 per 1000. Affected individuals absorb excessive amounts of dietary iron and over time, tissue iron deposition results in skin discoloration, arthropathy, hepatic cirrhosis, heart failure, diabetes mellitus and impotence. Early diagnosis and institution of phlebotomy treatments will prevent these manifestations and normalize life expectancy. Once organ damage is established many of the manifestations are irreversible. Since the early manifestations of the disease are subtle, a case can be made for routine screening. This conclusion is supported by cost-effectiveness analysis based on available data. A reasonable screening strategy would start with a serum transferrin saturation. A value ≥ 55% should trigger a repeat transferrin saturation in a fasting state and a serum ferritin level. If both these tests are abnormal, a liver biopsy with quantitative iron determination is the currently accepted confirmatory test.     

Pathogenesis of hereditary hemochromatosis

Hereditary hemochromatosis comprises several inherited disorders of iron homeostasis characterized by increased gastrointestinal iron absorpstion and resultant tissue iron deposition. The identification of HFE and other genes involved in iron metabolism has greatly expanded our understanding of hereditary hemochromatosis. Two major hypotheses have been proposed to explain the pathogenesis of HFE-related hereditary hemochromatosis: the hepcidin hypothesis and the duodenal crypt cell programming hypothesis.     

Hypogonadism in hereditary hemochromatosis

Hypogonadism, usually hypogonadotropic in origin, is the most common nondiabetic endocrinopathy in hereditary hemochromatosis (HH). Early studies, usually evaluating small numbers of patients with advanced HH, report prevalence rates of 10-100%. The clinical presentation of HH has changed in recent years as a result of increased awareness and screening. We assessed the prevalence of hypogonadism in a large group of patients with HH diagnosed in a single center over the past 20 yr, the period of follow-up spanning the time before and after widespread screening was introduced and the HFE gene was recognized. Abnormally low plasma testosterone levels, with low LH and FSH levels, were found in nine of 141 (6.4%) male patients tested. Eight of nine (89%) had associated hepatic cirrhosis; three of nine (33%) had diabetes. Inappropriately low LH and FSH levels were found in two of 38 females (5.2%) in whom the pituitary-gonadal axis could be assessed. This is the largest detailed study of hypogonadism reported in HH. The lower prevalence of hypogonadism compared with other reported series reflects the earlier diagnosis of HH in an unselected group of patients attending a single center. Patients with lesser degrees of hepatic siderosis at diagnosis are unlikely to develop hypogonadism.     

Arthritis in hereditary hemochromatosis

Seven pedigrees with 45 members were evaluated for arthropathy associated with hereditary hemochromatosis (HC). Patients with symptomatic extraarticular disease were compared with asymptomatic patients who had evidence of HC on laboratory findings, and with normal subjects. Patients who were homozygous for HC were compared with heterozygous patients and normal subjects. HC arthritis does not appear to be an early predictor of disease, and chondrocalcinosis is a late manifestation of HC arthropathy.