红细胞嘧啶5′-核苷酸酶缺乏症4例及文献复习

目的：了解红细胞嘧啶5′-核苷酸酶（P5′N）缺乏症的特点。方法：回顾性分析4例红细胞P5′N缺乏症患者的病历资料，并结合文献进行复习。结果：4例患者中3例为男性，1例女性。年龄范围7个月～33岁，病程7个月～17年。所有患者均有轻度至中度的贫血，均有脾脏肿大，红细胞P5′N活性均低于正常。结论：遗传性P5′N缺乏症是一种少见的遗传性非球形细胞溶血性贫血，本病的血液学特点与其他遗传性非球形细胞溶血性贫血的主要区别在于本病红细胞P5′N活性下降。本病尚无特效治疗措施，目前仍以支持治疗为主。     

人类微小病毒B_(19)在遗传性溶血性贫血患者中引起流行性急性纯红细胞再生障碍性贫血

作者对1984年美国俄亥俄州东北部发生的26例遗传性溶血性贫血患者的流行性纯红细胞再生障碍性贫血(下简称再障)作了调查。男14、女12例,年龄2～23岁。其中镰状细胞病20例,血红蛋白 SC 病4例,镰状细胞-β地中海贫血和遗传性球形细胞增多症各1例。这些病人在纯红细胞再障出现前1～17(中位数4)天都已有前驱症状:发热、畏寒、嗜睡或疲乏;85%有     

老年人遗传性球形细胞增多症

遗传性球形细胞增多症是一种先天性溶血性贫血,呈常染色体显性遗传,其特征是周围血中存在球形红细胞,它的渗透性脆性及机械性脆性均增加。主要临床表现有贫血、脾大及黄疸,常见于儿童及青少年。为预防反复发作有时是致命性的溶血及骨髓造血功能障碍,可行脾切除术。本文首次报道一组60～90岁患者的遗传性球形细胞增多症,5例均未切脾治疗。病例报告例1,女性,63岁,否认有贫血、黄疸、腿部溃疡的个人史及家族史,住院前6个月时常规血象正常。体检肝脾大,无黄疸。血红蛋白     

遗传性溶血性贫血

遗传性溶血性贫血是以溶血和溶血性贫血为主要临床表现的遗传性疾病,是全球最常见的遗传性疾病.按发病机制可分为遗传性红细胞膜缺陷、红细胞酶病和血红蛋白病三大类,最常见的疾病为遗传性球形红细胞增多症、葡萄糖-6-磷酸脱氢酶缺乏症和地中海贫血.临床表现具有异质性,疾病早期或轻型不一定有贫血.重视外周血红细胞形态检查可以及早发现本组疾病,普及灵敏度和特异度高的筛查试验将大大提高诊断率,各医学中心建立血红蛋白膜蛋白电泳、红细胞酶直接定量测定以及血红蛋白病的基因诊断和产前诊断将提高诊断正确率.     

红细胞嘧啶5′-核苷酸酶缺乏致溶血性贫血1例报道并文献复习

红细胞嘧啶5′-核苷酸酶缺乏症(pyrimidine 5′-nucleotide deficiency, P5′ND)是一种罕见的遗传性酶缺陷疾病，目前报道较少。文中病例反复出现溶血性贫血、黄疸、脾脏肿大，经完善红细胞酶学试验最终诊断为P5′ND。笔者结合相关文献复习认为，对于慢性非球形溶血性贫血患者，需警惕此类红细胞酶缺陷相关疾病，有条件者可尽量完善二代基因测序筛选致病基因，更好地指导临床实践。现特将其诊疗过程初步整理、总结并报道如下，以期为罕见病的诊治思路提供一定参考价值。     

丙酮酸激酶缺乏症36例临床资料分析

目的:探讨丙酮酸激酶(PK)缺乏症的临床特点、诊断、治疗及预后。方法:回顾性分析36例PK缺乏症患者的临床资料。结果:临床表现:36例患者中23例有不同程度的贫血貌,12例有皮肤和(或)巩膜黄染,脾大18例,肝大8例,尿色加深13例。实验室检查:全血细胞减少8例,36例患者红细胞均有不同程度的减少,血红蛋白低于正常值35例,血红蛋白正常1例,31例网织红细胞百分比增加。溶血检查:36例患者均存在PK活性缺乏,其中2例合并遗传性球形红细胞增多症,合并嘧啶5'核苷酸酶缺乏症1例,合并地中海贫血1例,继发于骨髓增生异常综合征4例,继发于再生障碍性贫血4例,继发于骨髓纤维化1例。结论:PK缺乏症病情严重程度不一,临床容易误诊、漏诊,目前无有效治疗手段,其治疗手段尚需进一步研究。     

丙酮酸激酶缺乏症36例临床资料分析

目的:探讨丙酮酸激酶(PK)缺乏症的临床特点、诊断、治疗及预后。方法:回顾性分析36例PK缺乏症患者的临床资料。结果:临床表现:36例患者中23例有不同程度的贫血貌,12例有皮肤和(或)巩膜黄染,脾大18例,肝大8例,尿色加深13例。实验室检查:全血细胞减少8例,36例患者红细胞均有不同程度的减少,血红蛋白低于正常值35例,血红蛋白正常1例,31例网织红细胞百分比增加。溶血检查:36例患者均存在PK活性缺乏,其中2例合并遗传性球形红细胞增多症,合并嘧啶5'核苷酸酶缺乏症1例,合并地中海贫血1例,继发于骨髓增生异常综合征4例,继发于再生障碍性贫血4例,继发于骨髓纤维化1例。结论:PK缺乏症病情严重程度不一,临床容易误诊、漏诊,目前无有效治疗手段,其治疗手段尚需进一步研究。     

儿童遗传性球形红细胞增多症

贫血在我国儿童疾病中列为四病之一,主要表现在营养性贫血方面。但溶血性贫血在我国儿童中也不少见。溶血性贫血在临床上有遗传因素与非遗传因素两种。遗传性因素中大致可分为(1)红细胞膜的缺陷;(2)红细胞代谢异常,如糖酵解代谢异常与核苷代谢异常,以及戊糖磷酸盐回路和谷胱苷肽代谢酶缺乏症等;(3)球蛋白结构与合成障碍,等等。遗传性球形红细胞增多症(HS)就是因红细胞膜有先天性的蛋白质异常或缺乏所致。此病常有家族发病史,一般属常染色体显性遗传。HS最早于1871年由Vanlair和Masius描述,当时称小红细胞症。Gooy Min-kouski观察到本病中球形红细胞有渗透脆性增高。1937年Castle和Daland提出溶血基础可能是红细胞结构异常。以后的学者逐渐注意到在本病中,脾脏及红细胞结构和功能在发病中的重要作用。HS在世界各种族中均有发现,在北欧本病为遗传性溶血最常见的一种类型,在我国     

血液病的外科手术问题

一、血液病的脾切除治疗问题脾切除是治疗某些血液病的重要手段之一,为此,正确掌握适应证及脾切除的疗效,并在临床工作中能及时正确应用,将对血液病患者的治疗起到积极的作用。(一)有脾切除术指征的血液病1.遗传性球形细胞增多症(HS):HS为一种常染色体显性遗传性疾病。主要临床表现有贫血、黄疽、脾肿大,为溶血性贫血的常见病。患者多在4～10岁发病,其病因是由于红细胞膜的内在缺陷产生大     

遗传性球形红细胞增多症患者外周血红细胞形态的扫描电镜观察

目的 :为探讨遗传性球形红细胞增多症异形红细胞的形态分类、发生演变、诊断和鉴别 ,本文运用扫描电镜技术对遗传性球形红细胞增多症患者外周血红细胞进行研究。方法 :7例遗传性球形红细胞增多症患者及 2例家系成员的静脉血置于扫描电镜下观察。结果 :在观察红细胞从盘形到口形 ,最终至球形的过程中 ,作者对各型红细胞直径和中央凹陷直径及细胞厚度的变化作了测量 ,并结合细胞表面形态和测量结果将病变红细胞分成 5个亚型 ,即 :盘口型 -碗口型 -球口型 -口球型 -典型球形 ,其他少量出现的异常红细胞 (棘状和靶状红细胞 )则归于畸变类。结论 :上述分型对于判断异形红细胞类型和诊断本病很有帮助。     

5'-Nucleotidase as a marker of both general and local inflammation in rheumatoid arthritis patients.

OBJECTIVES: To evaluate measurements of serum and synovial fluid 5'-nucleotidase (5'N) activity as a marker of general and local inflammation in arthritis, and to resolve a contradiction in the literature as to whether or not the activity of 5'N in the synovial fluids of rheumatoid arthritis (RA) patients is raised in comparison with that in the synovial fluids of other arthritis patients. METHODS: Assays for 5'N were carried out in the presence of inhibitors of other phosphatases, AMP deaminase and of 5'N itself. RESULTS: The 5'N activity in the synovial fluid of RA patients was both significantly higher (mean 1.7-fold) and had a greater variance than that in the synovial fluids of other arthritis patients, and the contradiction in the literature was resolved. There was a strong correlation between the 5'N activity in the sera of RA patients and their erythrocyte sedimentation rate. There was no significant correlation between the 5'N in the serum and synovial fluid for the RA patients, in marked contrast to the strong correlation between the two 5'N activities shown by the osteoarthritis patients. The 5'N activity was greater in the synovial fluid than in the serum for virtually all the patients, showing that it was being made locally. CONCLUSIONS: The 5'N activity in the serum (which came mostly from the liver) could be used as a marker of general inflammation, whereas the 5'N in the synovial fluid was mostly produced locally, and could be used as a marker of joint inflammation, particularly for the RA patients.     

Pyrimidine 5'-nucleotidase acquired deficiency in beta-thalassemia: involvement of enzyme-SH groups in the inactivation process

Pyrimidine 5'-nucleotidase (P5'N) partial deficiency has been described in several hematological disorders and also in the beta-thalassemic trait. To check if the P5'N deficiency in thalassemia was acquired we used thalassemic red cells (from either homo- or heterozygous subjects), whose P5'N activity was lower than in control cells. After separation on a density gradient, activity in lighter cells was similar to controls and less than 50% in denser cells. The most probable mechanism for this faster inactivation involves enzyme -SH groups modification by oxidation and reaction with monofunctional aldehydes produced by membrane lipid peroxidation. In vitro challenge of thiol enzymes as pyruvate kinase (PK), adenylate kinase (AK) and P5'N with increasing concentrations of GSSG, hexanal (HEX) and 4-hydroxynonenal (HNE), showed that HNE is the most powerful among the enzyme inhibitors tested and that P5'N activity is a more sensitive index of -SH groups damage, when compared to PK and AK.     

Inhibition of hexose monophosphate shunt in young erythrocytes by pyrimidine nucleotides in hereditary pyrimidine 5' nucleotidase deficiency

Recent reports have suggested that haemolytic anaemia in pyrimidine 5' nucleotidase (P5'N) deficiency might be due to impaired erythrocyte hexose monophosphate shunt (HMS). To investigate the relationship between pyrimidine accumulation, HMS impairment and shortened red-cell survival, we tested glucose 6-phosphate dehydrogenase (G-6PD), HMS, P5'N activities and the UV spectrum in whole red cells and in red cells of different age from 2 P5'N-deficient patients with different degrees of haemolytic anaemia. In whole red cells we found a reduction of both G-6PD and stimulated HMS activity in the presence of a variable amount of pyrimidine nucleotides (37.79 and 17.88 mumol/gHb respectively). A drastic inhibition of stimulated HMS activity was already present in the lightest red-cell fractions from patient 1, who presented a more severe haemolytic anaemia. The variable degree of pyrimidines found among red cell fractions, with a minor accumulation in the older red cells, supports the hypothesis that pyrimidine accumulation and HMS impairment occur in the younger erythrocytes of P5'N-deficient patients.     

Hereditary pyrimidine 5'-nucleotidase deficiency: from genetics to clinical manifestations

Hereditary pyrimidine 5'-nucleotidase (P5'N) deficiency is the most frequent abnormality of the red cell nucleotide metabolism causing hereditary non-spherocytic haemolytic anaemia. The disorder is usually characterised by mild-to-moderate haemolytic anaemia associated with the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. The precise mechanisms leading to the destruction of P5'N deficient red cells are still unclear. The pyrimidine 5'-nucleotidase type-I (P5'N-1) gene is localised on 7p15-p14 and the cDNA has been cloned and sequenced; 20 mutations have been identified so far in 30 unrelated families, most of them at the homozygous level. Recently, the comparison of recombinant mutants of human P5'N-1 with the wild-type enzyme has enabled the effects of amino acid replacements on the enzyme molecular properties to be determined and help to correlate genotype to clinical phenotype.     

四种常见贫血患者红细胞寿命的研究

目的:研究自身免疫性溶血性贫血(AIHA)患者的红细胞寿命,并与常见贫血患者的红细胞寿命比较。方法:回顾性分析AIHA、骨髓增生异常综合征(MDS)、重型再生障碍性贫血(SAA)和缺铁性贫血(IDA) 4组共55例患者的临床资料,以同期12例健康志愿者为正常对照组。采用一氧化碳(CO)呼气法测定红细胞寿命,比较4种贫血患者和健康志愿者红细胞寿命并作分析。结果:AIHA患者红细胞寿命为(30.41±31.12)d,比MDS(53.44±32.61)d、SAA(54.53±22.56)d和IDA(58.75±31.29)d患者的红细胞寿命均缩短(P0.05),4组患者红细胞寿命均较12例健康志愿者红细胞寿命(118.16±25.88)d显著缩短(P0.01)。结论:红细胞寿命缩短参与了AIHA、MDS、SAA和IDA患者贫血的发生,但在不同贫血疾病中所起作用程度不尽相同。     

Alterations of erythrocyte ATPase activity and oxygen consumption in patients with liver-blood deficiency syndrome

AIM: To investigate the pathophysiology of erythrocyte energy metabolic changes of patients with the traditional Chinese Medicine (TCM) liver-blood deficiency syndrome (LBDS).METHODS: Erythrocyte membrane ATPase activity and oxygen consumption rate (OCR) were determined in 66 patients with LBDS, including 35 patients with iron deficiency anemia and 31 patients with chronic aplastic anemia. Thirty healthy adults served as controls.RESULTS: ATPase activity and OCR were decreased in patients with LBDS.CONCLUSION: The decreased erythrocyte ATPase activity and OCR might cause the energy hypometabolism in LBDS patients.     

Alterations of ATPase activity and erythrocyte oxygen consumption in patients with liver-blood deficiency syndrome

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Molecular basis of pyrimidine 5'-nucleotidase deficiency caused by 3 newly identified missense mutations (c.187T>C, c.469G>C and c.740T>C) and a tabulation of known mutations

Hereditary pyrimidine 5'-nucleotidase deficiency is the most frequent enzymopathy of red blood cell nucleotide metabolism that causes hereditary non-spherocytic hemolytic anemia. The disease is usually characterized by mild-to-moderate hemolytic anemia, reticulocytosis and hyperbilirubinemia. To date, diagnosis ultimately depends upon demonstration of a reduced level of pyrimidine 5'-nucleotidase type-I (P5'N-1) activity in red cells and detection of mutations in the P5'N-1 gene. To unravel the causes of the P5'N deficiency and to obtain data for a definitive diagnosis three newly described missense mutations (c.187T>C, c.469G>C and c.740T>C) identified in patients with hemolytic anemia have been characterized at protein level. The mutant enzymes (C63R, G157R and I247T) were obtained as recombinant forms and purified to homogeneity. The enzymes were altered, although to a different extent, in both thermal stability and catalytic efficiency. The catalytic efficiency of all mutants was reduced especially towards UMP (up to more than 200 times), owing to the increased Km values (approximately, 10-25 times higher). The G157R enzyme was severely heat unstable and lost half of its activity after about 23 min of incubation at 37 degrees C. At higher temperature C63R and I247T mutants as well were less stable than the wild-type enzyme. Therefore, although the mutations targeted different regions of the P5'N-1 structure, they produced similar effects on the molecular properties of the enzyme. Thus, all affected amino acids are functionally and structurally important for preserving the enzyme activity during the red cell life span.     

Erythrocyte enzymes in polycythemia vera: a comparison to erythrocyte enzyme activities of patients with iron deficiency anemia

Fifteen cytoplasmic erythrocyte enzyme activities were determined in patients with polycythemia vera (PV), iron deficiency anemia (IDA), and a group of healthy volunteers. Among the PV patients, the erythrocyte enzyme activities were compared between 2 groups: patients treated solely with phlebotomy and patients treated with phlebotomy, Myleran (busulfan) and/or radioactive phosphorus 32P. Significant reduction in glutathione reductase activity was found in the PV group of patients. This activity was normalized by the addition of flavin adenine dinucleotide. In contrast to previous reports, no other enzyme activity was found to be significantly reduced. The activities of the enzymes known to be age-dependent were significantly elevated in all the groups tested except for phosphofructokinase and 3-phosphoglycerate mutase. The former was not elevated in any of the groups studied, while the latter was elevated only in the group of patients treated with Myleran and/or 32P. It was concluded that glutathione reductase (GR) deficiency is the only acquired enzyme deficiency in our group of PV patients and that radiation and chemotherapy did not induce further reduction in the activities of any of the enzymes tested. The possible involvement of GR deficiency in the etiology of the red cell life span shortening was discussed.