全身性遗传疾病对角膜移植排斥的影响

角膜移植为治疗角膜盲的主要手段，而角膜移植排斥则是决定角膜植片存活时间和病人术后视力的关键。角膜得益于其特殊的眼前节“免疫赦免”状态，使得角膜移植能够在众多器官移植中享有极低的排斥率，然而排斥反应发生的风险依然存在。当机体处于遗传物质异常的特殊状态时，宿主将通过宏观调控“免疫赦免”状态对植片的保护作用或受体对移植物排异产生的有害作用，延迟或促进角膜移植排斥反应的发生，进而影响移植物的存活时间和透明度。该文综述与角膜移植排斥相关的多种全身性遗传疾病，总结全身性遗传疾病对角膜移植排斥的影响，浅析其发生的病理生理学机制以及诊疗的特殊性。     

99Tcm-DMSA肾皮质显像诊断小儿肾发育不良

目的 探讨^99Tc^m—二巯基丁二酸(DMSA)肾皮质显像诊断小儿肾发育不良的价值。方法 疑为肾发育不良患儿29例，行常规^99Tc^m—DMSA肾皮质显像和腹部B超检查。图像分析：将发育不良肾分为0～4级。结果 ^99Tc^m—DMSA肾皮质显像示29例患儿中24例为单侧肾发育不良，其中11例1级，7例2级，6例3级，余5例患肾未显影为0级，结合其他：检查诊断为肾发育不良。患肾分肾功能为0～24．9％(平均6．3％)。29例患儿中24例患肾肾皮质显像诊断为肾发育不良，5例患肾未显影，由其他影像学方法确诊，诊断灵敏度为82．76％。29例中19例经手术治疗，病理检查证实为肾发育不良。结论 ^99Tc^m—DMSA肾皮质显像诊断肾发育不良灵敏度高、可靠，可确定发育不良肾部位和判断肾功能。     

Alkaptonuria in the Trenčín District of Czechoslovakia

For several years the Clinical Genetics Research Laboratory at Martin, Czechoslovakia, has been studying alkaptonuria (AU) in the northern part of the District of Tren?ín in Slovakia. These affected individuals are part of a group of 103 alkaptonurics originated mostly in the mountainous parts of Slovakia. We report results of pedigree analyses; population and affected-family biochemical urine screening; estimation of inbreeding coefficient, of exogamy rate and of average marital distance and of calculation of the frequency of the AU allele, and of homozygotes and jeterozygotes in this portion of the Tren?ín District. Twelve homozygotes were found, but seven originated from a single hamlet in which a founder effect – genetic drift and inbreeding – are thought to account for the high prevalance of AU.     

The molecular immunology of human susceptibility to fungal diseases: lessons from single gene defects of immunity

Introduction: Fungal diseases are a threat to human health. Therapies targeting the fungus continue to lead to disappointing results. Strategies targeting the host response represent unexplored opportunities for innovative treatments. To do so rationally requires the identification and neat delineation of critical mechanistic pathways that underpin human antifungal immunity. The study of humans with single-gene defects of the immune system, i.e. inborn errors of immunity (IEIs), provides a foundation for these paradigms.

Areas covered: A systematic literature search in PubMed, Scopus, and abstracts of international congresses was performed to review the history of genetic resistance/susceptibility to fungi and identify IEIs associated with fungal diseases. Immunologic mechanisms from relevant IEIs were integrated with current definitions and understandings of mycoses to establish a framework to map out critical immunobiological pathways of human antifungal immunity.

Expert opinion: Specific immune responses non-redundantly govern susceptibility to their corresponding mycoses. Defining these molecular pathways will guide the development of host-directed immunotherapies that precisely target distinct fungal diseases. These findings will pave the way for novel strategies in the treatment of these devastating infections.     

串联质谱技术在脂肪酸氧化代谢病诊断中的应用研究

目的探讨利用串联质谱技术检测干血滤纸片中酰基肉碱水平,诊断脂肪酸氧化代谢病。方法对象为2941例临床遗传性代谢病高危儿童,利用串联质谱技术检测患儿干血滤纸片中酰基肉碱水平,结合临床资料和常规生化结果,进行脂肪酸氧化代谢病诊断。结果诊断了14例脂肪酸氧化代谢病(0.5%),其中肉碱棕榈酰转移酶Ⅰ缺乏症1例,肉碱棕榈酰转移酶Ⅱ缺乏症1例,短链酰基辅酶A脱氢酶缺乏症1例,中链酰基辅酶A脱氢酶缺乏症7例,极长链酰基辅酶A脱氢酶缺乏症2例,多种酰基辅酶A脱氢酶缺乏症2例。结论通过串联质谱技术检测干血滤纸片中酰基肉碱水平,可对部分脂肪酸氧化代谢病进行诊断。     

PATHOLOGY OF LONG-CHAIN 3-HYDROXYACYL-COA DEHYDROGENASE DEFICIENCY CAUSED BY THE G1528C MUTATION

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is a recently discovered disorder affecting the mitochondrial-oxidation of fatty acids. There have been few reports of the pathologic findings in-oxidation defects. We examined pathologic specimens from 16 patients with this disorder (11 patients were homozygous for the common mutation G1528C, 5 patients were siblings with a similar clinical presentation). Autopsies were performed on all 15 patients who died, and liver biopsy specimens were available from 8 patients. Hepatomegaly and steatosis of the liver, found in every patient, were often combined with fibrosis or cirrhosis. Cardiomegaly and accumulation of fat in the myocardium, renal tubules, and skeletal muscle were found in many patients. A detailed neuropathologic examination was performed on six patients, and brain specimens obtained at autopsy were examined in four others. In general, neuropathologic findings were mild and unspecific, but vacuolization was detected in the deep gray matter and in the cerebellum and brain stem nuclei of five patients. In one patient the vacuolization was prominent; in the other four it was milder and more focal. The vacuoles seemed to be either in the neuropil or associated with swollen hydropic cells. The uniform pattern of histopathologic changes facilitates the diagnostics in this severe disorder, allowing opportunities for therapy and prenatal diagnosis.     

出生免疫错误相关的肝脾问题

目前已用出生免疫错误（IEI）来替代原发性免疫缺陷病这一概念。IEI是一类由单基因突变引起免疫功能异常的遗传性疾病，肝脏和脾脏作为人类重要的免疫器官，与IEI疾病过程中伴发感染、淋巴增殖及自身免疫现象等有重要关联。文章就与IEI相关的肝脾问题进行概述。     

海南省少数民族地区37 482例新生儿遗传代谢病筛查结果分析

目的探讨海南省少数民族地区新生儿多种遗传代谢病(IEM)的发病情况。 方法选择2018年1月1日至2020年1月31日，在海南省少数民族地区出生、监护人同意进行新生儿IEM筛查的37 482例新生儿为研究对象。采用串联质谱法，对新生儿足跟血(滤纸干血斑标本)进行新生儿多种IEM筛查，对结果疑似IEM的部分新生儿，釆集外周血进行基因检测，以确诊其IEM种类、基因突变情况。采用χ²检验，对海南省少数民族地区男性与女性患儿IEM最低发病率进行统计学比较。本研究经海南省人民医院医学伦理委员会批准[审批文号：医伦(2018)第14号]。 结果①海南省少数民族地区上述研究时间内出生的38 586例活产新生儿中，37 482例接受IEM筛查，新生儿IEM筛查覆盖率为97.1%。②37 482例新生儿中，筛查结果疑似IEM的新生儿为89例，其中24例接受基因检测，19例确诊为IEM，24例疑似IEM新生儿的IEM确诊率为79.2%(19/24)。由于仅部分可疑IEM新生儿接受基因检测，故海南省少数民族地区新生儿IEM最低发病率为51/10万(19/37 482)。其中，男性新生儿IEM最低发病率为57/10万(12/21 136)，女性为43/10万(7/16 346)，二者比较，差异无统计学意义(χ²＝0.354、P＝0.552)。③19例确诊IEM新生儿均发生基因突变，其中氨基酸代谢病为5例、有机酸代谢病为5例、尿素循环障碍为2例、脂肪酸β氧化代谢障碍为7例。 结论海南省少数民族地区新生儿IEM发病率较高、种类较多。建议在海南省少数民族地区开展新生儿多种IEM筛查，改善IEM新生儿生活质量。