家族聚集性发病心肌致密化不全四例临床分析

目的探讨心肌致密化不全患者的临床特点,诊断及鉴别诊断,提高家族遗传性人群的检出率。方法回顾性分析同一家族的临床表现及超声心动图辅助检查资料。结果本家庭中4人检出心肌致密化不全,且每例患者症状表现均不相同。结论心肌致密化不全临床具有家族遗传倾向,且临床病程迁延,表现各异,容易漏诊和误诊,在出现首例心肌致密化不全发病患者后,早期心脏超声心动图是重要的诊断和筛查手段。     

全国2009年新生儿遗传代谢病筛查项目切值分析

[目的]了解我国新生儿遗传代谢病筛查检验项目切值情况,为新生儿遗传代谢病筛查工作提供建议.[方法]问卷调查收集2009年参加卫生部临床检验中心新生儿筛查室间质量评价计划单位的结果,包括实验室编码、单位名称、所在地区、两个质量评价项目(苯丙氨酸和促甲状腺素)的切值、所用方法、仪器、试剂和校准物.分析不同地区和方法学原理对两个项目切值大小的影响. [结果]发放问卷167家,包括了参加卫生部临床检验中心新生儿筛查室问质最评价计划的所有单位.收到159份问卷,其中有效问卷152份.回收率和有效率分别达到95.2%和95.6%.参加研究的机构数量最多的3个省份分别是广东(20家)、辽宁(14家)和山东(14家).苯丙氨酸的切值分析有三种方法学原理:荧光分析法,占73.0%(111/152),最大和最小切值分别为4.0 mg/dL和1.7 mg/dL;细菌抑制法,占14.5%(22/152),最大和最小切值分别为4.0 mg/dL和1.9 mg/dL;定量酶法,占11.8%(18/152),最大和最小切值分别为2.8 mg/dL和2.0 mg/dL;其他方法1家,占0.7%(1/152).促甲状腺素的切值分析有三种方法学原理:时间分辨荧光分析法,占63.2%(96/152),最大和最小切值分别为20.0μU/mL和4.9 μU/mL;酶免疫荧光分析法,占14.5%(22/152)最大和最小切值分别为12.0μU/mL和8.5μU/mL酶联免疫吸附法,占21.0%(32/152)最大和最小切值分别为15.0μU/mL和4.6μU/mL;其他方法2家,占1.3%(2/152).对于苯丙氨酸的测量,定量酶法是切值差别最小的方法;对于促甲状腺素的测量,三种方法切值的平均值基本相同,酶免疫荧光分析法的切值差别最小. [结论]对于同一检测项目,不同方法内切值差异较大,而方法间差异较小,建议对现有不同方法的切值进行确认或验证.     

儿童遗传代谢性脑病的诊断及治疗

多种遗传代谢病因代谢障碍导致高血氨、低血糖、酸中毒以及能量缺乏等,引起脑功能障碍,产生急性代谢性脑病,危及生命。急性期的辅助检查,对早期诊断,恰当治疗至关重要。积极的支持治疗,清除有毒代谢产物治疗,提供相应的维生素和辅助因子,特异性的药物治疗以及特殊饮食治疗,可以提高生存率,减少后遗症。     

先天性无虹膜二家系报道并文献复习

先天性无虹膜为一罕见而严重的眼科疾病,以虹膜发育不良为最显著特征,并多伴发角膜混浊、白内障、青光眼、斜视等异常,通常为常染色体异常的遗传性疾病。我们将对在四川大学华西医院眼科门诊中发现的2个先天性无虹膜家系进行报告,并对其病因、临床表现、治疗与预防作一复习及总结。     

并指（趾）畸形的分类及遗传学研究进展

并指（趾）畸形（syndactyly,SD）是最常见的遗传性肢体畸形,表现为某些手指或脚趾的融合。这类畸形可单独出现,也可以作为300多种综合征的一个体征出现。SD在家庭间及家庭内部具有显著的临床异质性。即使在同一个体中,表型也可表现为单侧或双侧,对称或不对称。目前,已经报道的非综合征型的SD至少9种,主要遗传模式为常染色体显性遗传,其次是常染色体隐性遗传及X-连锁隐性遗传。其中Ⅱ-a,Ⅲ,Ⅳ,Ⅴ,Ⅶ,Ⅷ型的SD致病基因及其突变位点已经找到,其他SD的遗传学机制仍然未知。在Sajid Malik分类的基础上,系统总结近几年SD的遗传研究成果,以期为该病机制的深入研究和临床诊断提供帮助。     

Diagnostic determination system for high-risk screening for inborn errors of bile acid metabolism based on an analysis of urinary bile acids using gas chromatography–mass spectrometry: Results for 10 years in Japan

Background:  Some patients with cholestasis of unknown cause may have inborn errors of bile acid metabolism (IEBAM) thus causing abnormalities of bile acid biosynthesis. Although seven types of bile acid synthetic defects have thus far been reported for this disorder, no detailed information on its incidence and so on in Japan is yet available. In order to elucidate the current status of IEBAM in Japan, in July 1996 a diagnostic determination system was established for high-risk screening for IEBAM.
Methods:  Urinary bile acids were analyzed on gas chromatography–mass spectrometry (GC-MS) and quantitative analysis was done using selected ion monitoring (SIM).
Results and conclusions:  In a total of 576 samples analyzed over the 10 year period prior to June 2005, 159 patients were found with cholestasis of unknown etiology. Of these patients, 10 (6.3%) were found to have IEBAM by this system, while 91 (61.1%) had cholestasis without a definitive diagnosis. This diagnostic determination system with GC-MS of urinary bile acids is therefore considered useful for detecting IEBAM.     

预防接种与遗传代谢性疾病

<正>预防接种泛指用人工制备的疫苗类制剂(抗原)或免疫血清类制剂(抗体)通过适宜的途径接种到机体,使个体和群体产生对某种传染病的自动免疫或被动免疫,其目的     

3-Ureidopropionate contributes to the neuropathology of 3-ureidopropionase deficiency and severe propionic aciduria: a hypothesis.

3-Ureidopropionate (3-UPA) is a physiologic metabolite in pyrimidine degradation. Pathological accumulation of 3-UPA in body fluids is found in 3-ureidopropionase deficiency and severe forms of propionic aciduria. Both diseases clinically present with a severe neuropathology involving gray and white matter as well as with a dystonic dyskinetic movement disorder. To date nothing is known about the toxic nature of this metabolite. The aim of the present study was to elucidate whether 3-UPA may act as endogenous neurotoxin. Exposure of cultured chick neurons to 3-UPA induced a concentration- and time-dependent neurodegeneration. Neuronal damage was reduced by the antioxidant alpha-tocopherol and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. In contrast, the non-NMDA receptor antagonist CNQX, the metabotropic glutamate receptor antagonist L-AP3, and succinate showed no protective effect. Furthermore, 3-UPA elicited an increased production of reactive oxygen species followed by a delayed increase in intracellular calcium concentrations. Activity measurement of single respiratory chain complexes I-V revealed an inhibition of complex V activity, but not of the electron-transferring complexes I-IV by 3-UPA. In contrast, 3-UPA did not affect the mitochondrial beta-oxidation of fatty acids. In conclusion, our results provide strong evidence that 3-UPA acts as endogenous neurotoxin via inhibition of mitochondrial energy metabolism, resulting in the initiation of secondary, energy-dependent excitotoxic mechanisms.     

Evaluation and management of patients with propionic acidemia undergoing liver transplantation: a comprehensive review

Propionic acidemia is a rare metabolic disorder that often results in episodic hyperammonemia, basal ganglia infarction, mental retardation, and cardiomyopathy. OLT has been used as a treatment for propionic acidemia, but its benefit in patients with this disease is unclear. The current study was undertaken to clarify the role of OLT in the management of this disease. The medical literature, a national registry of US OLT recipients, and a single institution liver transplant experience were reviewed for cases of OLT for propionic acidemia. Accumulated cases demonstrate that OLT has resulted in clear evidence of clinical improvement in several patients, often obviating the need for dietary restriction or other forms of medical management. OLT appears to halt the decline in neurocognitive function often associated with propionic acidemia. In total, 12 patients with propionic acidemia have undergone a total of 14 OLTs. A quantitative analysis of outcomes shows an overall patient survival rate of 72.2% at one year after OLT. In conclusion, OLT should be considered a treatment option for patients with propionic acidemia who continue to experience episodes of hyperammonemia in spite of maximal medical therapy. Early OLT may limit the development of mental retardation and/or cardiomyopathy.     

串联质谱法检测结果阴性的甲基丙二酸血症合并同型半胱氨酸血症 cblX型患儿一例

一例甲基丙二酸血症合并同型半胱氨酸血症cblX型患儿在婴儿早期出现局灶性癫痫发作和癫痫性痉挛发作，多种抗癫痫药物治疗效果不佳，患儿于4月龄时死亡。新生儿筛查和急性发作期串联质谱法检测均未见明显异常，超高效液相色谱 - 串联质谱法检测提示血甲基丙二酸和同型半胱氨酸增高，全外显子组测序显示 HCFC1基因存在c.202C>G（p.Q68E）半合子突变，遗传自其母亲。