《丙酸血症介绍(medline 版).doc》由会员分享，可在线阅读，更多相关《丙酸血症介绍(medline 版).doc（11页珍藏版）》请在金锄头文库上搜索。
1、PROPIONICACIDEMIAPROPIONYL-CoA CARBOXYLASE DEFICIENCYPCC DEFICIENCYGLYCINEMIA, KETOTICHYPERGLYCINEMIA WITH KETOACIDOSIS AND LEUKOPENIAKETOTIC HYPERGLYCINEMIA丙酰辅酶A羧化酶缺乏症甘氨酸血症，酮症，伴高甘氨酸血症的酮症酸中毒和白细胞减少症酮症性高甘氨酸血症Phenotype Gene RelationshipsLocationPhenotypePhenotypeMIM numberGene/LocusGene/LocusMIM number
2、3q22.3Propionicacidemia606054PCCB23205013q32.3Propionicacidemia606054PCCA232000Clinical SynopsisA number sign (#) is used with this entry because propionic acidemia is caused by mutation in the genes encoding propionyl-CoA carboxylase, PCCA (232000) or PCCB (232050). Cells from patients with mutatio
3、ns in the PCCA gene fall into complementation group pccA. Cells from patients with mutations in the PCCB gene fall into complementation group pccBC. Mutations in the pccB subgroup occur in the N terminus of the PCCB gene, which includes the biotin-binding site, whereas mutations in the pccC subgroup
4、 occur in the C terminus of the PCCB gene (Fenton et al., 2001).临床概要数字符号（）用于标志此项目，因为丙酸血症是由于编码丙酰辅酶A羧化酶的基因突变；，PCCA（232000），PCCB（232050）。患儿突变的细胞中，PCCA基因下降到互补组形成pccA。PCCB基因下移互补组成pccBC，pccB亚组的突变发生在PCCB基因的N终端，其中包括生物素结合位点，而在PccC亚组突变发生在PCCB基因的C端，（芬顿等，2001）。Clinical FeaturesThe features of propionic acidemia
5、 are episodic vomiting, lethargy and ketosis, neutropenia, periodic thrombocytopenia, hypogammaglobulinemia, developmental retardation, and intolerance to protein. Outstanding chemical features are hyperglycinemia and hyperglycinuria. This disorder is not to be confused with hereditary glycinuria (1
6、38500), which is presumably transmitted as a dominant.临床特点丙酸血症的特点是发作性呕吐，嗜睡和酮症，中性粒细胞减少症，周期性血小板减少症，免疫球蛋白低下，发育迟缓，蛋白质不耐受。杰出的化学特征是高甘氨酸血症与高氨酸尿症；这种疾病与遗传性甘氨酸尿症可以容易鉴别（138500可能是显性遗传），Soriano et al. (1967) suggested that in the disorder first described by Childs et al. (1961), a generalized defect in utilizati
7、on of amino acids results in excessive deamination of certain amino acids in muscle, with consequent hyperammonemia and ketoacidosis. In a second group of patients whose disorder is also termed hyperglycinemia, ketoacidosis, neutropenia, and thrombocytopenia have not been observed and glycine is the
8、 only amino acid present in excess in serum and urine; see glycine encephalopathy (605899).索里亚诺等人 （1967）提出建议，在（1961年）chlids等仍描述这种缺陷病。可能是常见的氨基酸利用障碍，使肌肉中的某些氨基酸脱氨过多，导致的高氨血症和酮症酸中毒，第二组的疾病中也观察到高甘氨酸血症，但酮症酸中毒，中性粒细胞和血小板减少并未被观察到。在血清和尿液中仅发现过量的甘氨酸；还有甘氨酸脑病（605899）。Hsia et al. (1969) studied fibroblasts from a si
9、ster of the boy described by Childs et al. (1961) and demonstrated deficient propionate carboxylation as the basic defect in ketotic hyperglycinemia. Hsia et al. (1971) also showed that ketotic hyperglycinemia is the same as propionic acidemia and is the result of a defect in PCC. In further studies
10、 on this patient, Brandt et al. (1974) demonstrated that with low protein diet, growth and intelligence developed normally to age 9 years; indeed, intelligence was superior. The family originally reported by Childs et al. (1961) had the pccA type of propionic acidemia (Wolf, 1986).Hsia等（1969）研究了从193
11、1尿child等描述的患儿姐姐的成纤维细胞，并证明有缺陷的基本在丙酰羧化酶。 Hsia等（1971）也表明，酮症性高甘氨酸血症即是丙酸血症；是PCC缺陷的结果。在这个病人勃兰特等人的进一步研究（1974年）表明，以低蛋白饮食喂养，生长和智力发育在9岁接近正常，甚至智力发育尤甚。Chlids （1961年）最初报道的家族史为，丙酸血pccA类型的丙酸血症（沃尔夫，1986）。In a male Pakistani offspring of first-cousin parents, Gompertz et al. (1970) described acidosis and ketosis due
12、 to propionic acidemia, leading to death at 8 days of age. A sib had died at 2 weeks of age with metabolic acidosis and ketonuria. The defect was found to involve mitochondrial propionyl-CoA carboxylase. The same condition was described by Hommes et al. (1968).在一个巴基斯坦堂兄妹的男婴患儿，Gompertz （1970）描述性源于PA的
13、酸中毒和酮症，导致生后8天死亡。一个同胞2周龄死于代谢性酸中毒和酮尿。缺陷涉及线粒体丙酰辅酶A羧化酶。HOMMES等描述过类似的案例（1968年）。Al Essa et al. (1998) pointed out that not only do acute intercurrent infections precipitate acidosis in propionic acidemia, but such infections are unusually frequent in propionic acidemia in Saudi Arabia. Propionic acidemia
14、is unusually frequent in Saudi Arabia, with a frequency of 1 in 2,000 to 1 in 5,000, depending on the region. The disorder has a severe phenotype in Saudi Arabia. Al Essa et al. (1998) had information on approximately 90 patients; certain tribes accounted for almost 80% of these cases, suggesting a
15、founder effect. The number of other cases of organic acidemias observed during the same period was 656. Longitudinal data, in some instances up to 8 years, were available for 38 patients with propionic acidemia. A high frequency of infections was observed in 80% of the patients. Most microorganisms
16、implicated were unusual, suggesting an underlying immune deficiency. The infections occurred despite aggressive treatment with appropriate diets, carnitine, and, during acute episodes of the disease, with metronidazole, which suggested a global effect of the disease on T and B lymphocytes as well as on the bone marrow cells
