LSIT

描述：（改编自研究者摘要） 原卟啉症（EPP）是由遗传决定的， 血红素合成酶铁螯合酶（FC）活性缺陷， 导致红细胞、血浆、肝脏和肝脏中原卟啉（PP）蓄积， 粪便PP会导致疼痛的皮肤光敏性，并可能导致致命 肝毒性 关于EPP的自然过程仍有许多未知之处， 其发病机制和遗传方式。 继续 正在进行的已建立的EPP研究的纵向调查 人口与标准化的协议，并建立现有的数据库 在10年以上的24个不同种族背景的主题，将进一步 阐明疾病的自然过程。 个别患者可能 从早期发现肝功能的不良变化中获益。 可了解导致致死性肝毒性发展的因素 从回顾性分析数据库的患者谁开发 肝功能不全与人口数据相比， 整体关于在一个给定的时间段中FC的缺陷活性的方差的信息， 不同的美国EPP人口将通过测量其 患者、家庭成员和对照组的白细胞水平。 这 信息也将有助于建立遗传模式（S） 这种疾病可能很复杂。 分子遗传学研究 限制性片段长度多态性、检测和描述 基因突变）将继续在遗传物质分离， 患者、家庭成员和对照的血液，以进一步确定 EPP的遗传异质性，并将与临床相关 血液中卟啉负荷和代谢平衡， 粪便分布区室和FC活性在这个不同的EPP 人口 不寻常的病例的临床和实验室评价 几种相关形式的卟啉症将继续作为一个国家 实验室的资源功能。 免疫定位 表皮-真皮分离的显微解剖水平和直接 水疱中免疫反应物免疫电镜定位 卟啉症和"假卟啉症"的形式将在皮肤中进行 这些疾病患者的活检标本，以检查 它们之间的相似或不同之处，并针对适当的 基底膜区的生物分子成分，以供进一步研究。 B和C型肝炎病毒暴露与 美国的散发性与家族性迟发性皮肤卟啉症（PCT） 将通过PCT血液标本的多中心研究确定 检查病毒感染证据的患者，卟啉水平 积累和尿卟啉原脱羧酶活性。这 信息，以及相关的历史、体格检查和临床 将分析实验室数据的统计学显著性 相关性

DESCRIPTION: (Adapted from investigator's abstract) Erythropoietic protoporphyria (EPP) arises from genetically determined partially deficient activity of the heme synthetic enzyme ferrochelatase (FC) that causes accumulation of protoporphyrin (PP) in rbc, plasma, liver and feces. PP causespainful cutaneous photosensitivity and may lead to fatal hepatotoxicity. Much remains unknown about the natural course of EPP, its pathogenetic mechanisms and inheritance patterns. Continuation of ongoing longitudinal investigations of an established EPP study population with a standardized protocol, and an existing data base built over 10 years in 24 subjects of diverse ethnic backgrounds, will further elucidate the natural course of the disease. Individual patients may benefit from early detection of adverse changes in hepatic function. Factors leading to development of fatal hepatotoxicity may be learned from retrospective analysis of the data base for patients who develop liver dysfunction when compared with the data of the population as a whole. Information about the variance in defective activity of FC in a diverse United States EPP population will be gained by measuring its levels in leukocytes of patients, family members and controls. This information will also aid in establishing the inheritance pattern(s) of the disease, which may be complex. Molecular genetic studies (restriction fragment length polymorphisms, detection and description of gene mutations) will be continued in genetic material isolated from blood of patients, family members and controls to further define the genetic heterogeneity of EPP, and will be correlated with clinical symptomatology, porphyrin burden and metabolic balance in blood and fecal distribution compartments, and FC activity in this diverse EPP population. Clinical and laboratory evaluations of unusual cases of several related forms of porphyria will be continued as a national resource function of the laboratory. Immunomapping of the microanatomical level of the epidermal-dermal separation and direct immunoelectron microscopic localization of immune reactants in blistering forms of porphyrias and "pseudoporphyrias" will be performed in skin biopsy specimens of patients with these disorders, to examine similarities or differences among them, and to target appropriate biomolecular components of the basement membrane zone for further study. The prevalence of the association of hepatitis B and C viral exposure and sporadic vs. familial porphyria cutanea tarda (PCT) in the United States will be determined by a multicenter study of blood specimens from PCT patients examining evidence of viral infection, levels of porphyrin accumulation and uroporphyrinogen decarboxylase activity. This information, and relevant historical, physical examination, and clinical laboratory data will be analyzed for statistically significant correlations.