新生儿高氨血症30例

目的 探讨新生儿高氨血症的病因分布、临床特点、治疗措施及预后,提高对新生儿高氨血症的早期诊断率及预后判断.方法 对广州市妇女儿童医疗中心新生儿科2005年1月-2010年8月收治的30例高氨血症新生儿的临床表现、实验室检查、治疗效果等进行回顾性分析.结果 本组新生儿高氨血症病因为遗传性尿素循环障碍、丙酸血症、甲基丙二酸血/尿症、异戊酸血症、戊二酸血症.一过性高氨血症及获得性高氨血症,其首发症状主要为反应差、呼吸急促,其他有吸吮无力、喂养困难、发绀、呻吟、呕吐等;主要体征有意识障碍、四肢肌张力改变、肝脏大;主要实验室检查改变有血常规异常、高乳酸血症、代谢性酸中毒、头颅B超异常、电解质紊乱、凝血功能障碍及血/尿氨基酸异常.住院期间高氨血症病死率为46.67%,死亡病例血氨水平为(1 284.86±746.09) μmol·L-1,明显高于自动出院患儿血氨水平(335.11±172.57) μmol·L-1(t=4.621,P＜0.001)及治愈患儿的血氨水平(219.65±22.32) μmol·L-1(t=5.334,P＜0.001).结论 临床上出现不明原因的反应差、呼吸急促、喂养困难、呕吐等症状需注意高氨血症,应及早行血氨、血/尿代谢检查明确诊断.一旦诊断为高氨血症,应早期干预,降低病死率及减少后遗症的发生,并定期复查血氨水平来判断患儿的预后.     

NICU中先天性遗传代谢病的临床特点

目的 提高NICU医生对新生儿期起病的遗传代谢病的认识,做到早期诊断.方法 对2004年12月至2007年10月NICU中原因不明的严重酸中毒、拒乳、惊厥等新生儿进行尿气相色谱-质谱分析,同时部分检测血乳酸、血氨等.结果 10例新生儿确诊为先天性遗传代谢病,分别为尿素循环障碍2例,酪氨酸血症并瓜氨酸血症、甲基苯乙酸并异戊二酸血症、异戊二酸并甲基丙二酸血症、鸟氨酸血症、半乳糖血症、脂质代谢病、甲基丙二酸血症、异戊酸血症各1例.结论 NICU医生应掌握新生儿先天性遗传代谢病的特点,利用现有技术可以提高早期诊断率.     

精氨酰琥珀酸尿症致反复高氨血症1 例报告

目的探讨精氨酰琥珀酸尿症致反复高氨血症的诊断和治疗。方法回顾分析1例精氨酰琥珀酸尿症患儿的诊治及随访经过,并复习相关文献。结果患儿,男,13个月,因呕吐、嗜睡、反应差入院,检查发现血氨升高(138.02μmol/L),肝功能异常,伴低钾血症,血瓜氨酸升高(65.64μmol/L);脑电图异常。完善高氨血症相关基因的二代基因测序,发现精氨酰琥珀酸裂解酶基因(ASL)复合杂合突变。予以限制蛋白饮食、补充精氨酸治疗,患儿高氨血症仍反复发作,肝脏进行性增大;确诊1年后行肝移植。移植后1年,患儿肝功能、血氨无异常,生长发育无异常。结论精氨酰琥珀酸尿症临床表现复杂,高氨血症是其重要表现;基因检查有助确诊,肝移植治疗有效。     

深圳市1998-2008年新生儿疾病筛查结果分析

目的 分析深圳市新生儿疾病筛查结果,对筛查检出率等进行探讨.方法 应用自动连续微量流动荧光分析技术、荧光酶免法、酶联免疫法、细菌抑制法等技术,检测出生3 d新生儿足跟血干血片中苯丙氨酸、促甲状腺素、总半乳糖含量及葡萄糖6磷酸脱氢酶活性,进行苯丙酮尿症、甲状腺功能减低症、半乳糖血症、葡萄糖6磷酸脱氢酶缺乏症的筛查.结果 1998至2008年筛查了深圳市782630名新生儿,检出持续性高苯丙氨酸血症27例(经典型苯丙酮尿症15例,高苯丙氨酸血症8例,四氢喋呤缺乏症4例),甲状腺功能减低症458例,2002年8月至2008年12月筛查新生儿631 878名,检出高半乳糖血症12例,葡萄糖6磷酸脱氢酶缺乏症4937例.结论 新生儿疾病筛查是避免先天性遗传代谢病所致智障残疾等发生的有效措施之一.     

citrin缺陷导致的新生儿肝内胆汁淤积症12例临床和实验室研究

目的探讨citrin缺陷导致的新生儿肝内胆汁淤积症（NICCD）患儿的临床表现和实验室检查的特点。方法对12例肝内胆汁淤积和黄疸患儿进行常规实验室检查，结合血串联质谱分析、尿气相色谱质谱分析诊断为NICCD。对确诊患儿的临床表现、常规实验室检查、血氨基酸谱和酰基肉碱谱、尿有机酸等进行分析。结果NICCD患儿出生体重偏低。实验室改变包括γ-谷氨酰转移酶、碱性磷酸酶以及甲胎蛋白升高、高胆红素血症、低蛋白血症、凝血酶原时间延长。有明显低血糖6例，有轻度高氨血症3例，有半乳糖血症仅1例。3例肝活检病理提示肝内胆汁淤积和肝细胞脂肪变性。串联质谱分析发现多数患儿有特异性瓜氨酸、蛋氨酸、苏氨酸和酪氨酸明显升高，以及游离肉碱、C2、C3和长链酰基肉碱升高。尿气相色谱质谱有机酸分析有尿4-羟基苯乳酸、4-羟基苯丙酮酸和4-羟基苯乙酸升高。结论不明原因黄疸患儿鉴别诊断应考虑到NICCD，早期进行串联质谱分析对明确NICCD的诊断具有重要意义。     

高胰岛素血症伴高氨血症综合征1例报告并文献复习

目的探讨GLUD1基因变异所致高胰岛素血症伴高氨血症综合征临床表现和致病基因特点。方法回顾分析1例高胰岛素血症伴高氨血症综合征患儿的临床资料,并复习相关文献。结果女性患儿,1岁9个月起病,反复出现血糖偏低2年余,并惊厥发作3次,给予升血糖、止惊对症处理后可缓解;伴血胰岛素、血氨水平升高,诊断为高胰岛素血症伴高氨血症综合征。高通量测序发现患儿GLUD1基因存在错义变异c.965GA,p.Arg322His(杂合),其父母该位点均为正常基因型,为新生突变。结论基因检测有助于明确高胰岛素血症伴高氨血症综合征诊断。     

100例新生儿血氨值测定

为探讨新生儿高氨血症(NHA)的原因及高氨血症对新生儿行为能力的影响,我们对100例新生儿进行了血氨值测定。对象和方法采用微量扩散法(日本试剂),对1985年10月至1986年3月生于佳木斯医学院100例出生72小时     

未成熟儿—过性高氨血症

新生儿高氨血症包括从氨生成尿素的尿素循环中的先天性酶缺陷症等。这些疾患呈现的高氨血症通常持续一生,呈现各种症状而不消退。但是,未成熟儿发生的高氨血症无症状,而且到生后3周左右自然消退,其后不再复发,一般称之为无症状性一过性高氨血症。与此不同的是,极小未成熟儿可见到一过性高氨血症,伴发昏睡、痉挛等症状。不管有无症状,高氨血症为一过性,则提示其发病可能与尿素循环中的     

新生儿瓜氨酸血症Ⅰ型一家系基因分析

目的分析新生儿瓜氨酸血症Ⅰ型家系的基因变异特征。方法回顾分析1例新生儿瓜氨酸血症Ⅰ型患儿的临床资料,提取患儿及其父母外周血基因组DNA,采用二代测序技术进行基因检测,Sanger测序、生物信息学分析和定量PCR进一步验证测序结果。结果女性患儿,出生后反应差、四肢不规则抖动、肌张力增高,逐渐出现呼吸衰竭;血氨、血乳酸升高,血糖降低。血串联质谱检查提示瓜氨酸显著增高,尿气相色谱质谱检查提示尿乳清酸显著增高。基因检测发现患儿ASS 1基因c.1194-2A>G和3号外显子缺失复合杂合变异,其中c.1194-2A>G遗传自父亲,3号外显子缺失遗传自母亲,两种变异在HGMD数据库中均未报道,根据ACMG指南划分为可能致病性变异。结论ASS1基因c.1194-2A>G杂合变异和3号外显子杂合缺失是该新生儿瓜氨酸血症Ⅰ型的遗传学病因,丰富了中国人新生儿ASS 1基因变异谱。     

新生儿高氨血症的早期诊断及精准干预

新生儿高氨血症(NHA)是一种发生在新生儿期的危重症，发展迅速、死亡率高。新生儿期多种遗传和非遗传疾病可导致血氨增高，其病因复杂，如尿素循环障碍、有机酸血症、脂肪酸代谢病以及其他严重全身疾病均可导致获得性高氨血症。临床表现缺乏特异性，及早发现，明确病因，可通过喂养管理、降氨药物以及血液透析等进行精准干预，改善预后。     

Hyperammonemia in hypoglycemic preterm neonates

Plasma glucose, blood urea nitrogen, and ammonia were measured simultaneously in 44 newborns a few hours after birth. When the concentration of plasma glucose was below 30 mg/dl, plasma ammonia concentration was significantly higher (129 +/- 67 mumol/l) than in normoglycemic infants (74 +/- 33 mumol/l; p less than 0.01). Blood urea nitrogen was slightly lower in hypoglycemic infants (3.65 +/- 0.7 mmol/l) than in the control group (4.5 +/- 1 mmol/l) but the difference was not significant. These data show that hyperammonemia can be associated to hypoglycemia in low birth weight infants. Therefore, further investigations are required to determine the link between urea and glucose production rates in hypoglycemic newborns and whether hyperammonemia participates in the deleterious effects of hypoglycemia on the neonatal brain.     

Two Siblings with Complete Carbamyl Phosphate Synthetase I Deficiency

A female infant, who showed hyperammonemia in the neonatal period, died on 43rd postnatal day. Her female sibling also died on 42nd day after birth with an identical clinical picture and hyperammonemia. Urinary organic acids were negative in both cases. Their blood amino acids showed no specific pattern, and urinary orotic acid excretion was normal. The first two urea cycle enzymes and N-acetyl L-glutamate synthetase of the liver tissues of these two infants obtained at autopsy were assayed. They revealed a selective deficiency of carbamyl phosphate synthetase I.     

Diagnostic value of orotic acid excretion in heritable disorders of the urea cycle and in hyperammonemia due to organic acidurias

Orotic acid excretion in urine is increased in ornithine transcarbamylase deficiency, citrullinemia and argininemia; it is barely increased in argininosuccinic aciduria and normal in carbamylphosphate synthetase deficiency and in hyperammonemia due to organic aciduria. The determination of orotic acid excretion is useful in differentiating the causes of hyperammonemia and reduces the need for enzymatic assays on tissue biopsies for decisions on therapy. The data indicate that orotic acid does not merely reflect ammonia concentration in plasma, but depends on carbamylphosphate concentration. Arginine could play a key role in the regulation of ammonia detoxication.Supported by grant No. 3.591-0.75 of the Swiss National Science Foundation     

吸毒孕妇所生新生儿临床结局分析

目的 分析吸毒孕妇围生儿的临床结局.方法 回顾性分析105例吸毒孕妇所生新生儿的临床资料,包括早产儿、低体重儿、新生儿窒息、新生儿呼吸窘迫综合征(neonatal respiratory distress syndrome,NRDS)、颅内出血、先天畸形及死亡,并与50例健康孕妇所生的新生儿(对照组)进行比较,同时观察新生儿戒断综合征的发生情况.结果 105例吸毒孕妇中,自然分娩80例,剖宫产25例.早产56例(53.3％),平均出生体重(2 534±1 234)g,新生儿窒息25例(23.8％),NRDS 18例(17.1％),颅内出血16例(15.2％),先天畸形3例(2.9％).吸毒孕妇所生新生儿胎龄及出生体重低于对照组,吸毒孕妇围生儿发生早产、低体重儿、新生儿窒息、NRDS及颅内出血的比例高于对照组,差异有统计学意义(P＜0.05).与吸毒时间≤2年者比较,吸毒时间＞2年者所生新生儿早产、低体重儿、新生儿窒息、NRDS的比例更高,差异有统计学意义(P＜0.05).静脉注射吸毒孕妇发生早产、低体重儿、新生儿窒息、NRDS的比例高于口服吸毒者,差异有统计学意义(P＜0.05).吸毒组新生儿红细胞、白细胞、天门冬氨酸氨基转移酶、丙氨酸转氨酶高于对照组,血小板及白蛋白低于对照组,差异有统计学意义(P＜0.05).共30例新生儿出现新生儿戒断综合征表现.105例新生儿中治愈99例,死亡6例,死亡原因包括3例NRDS合并肺部感染,1例严重颅内出血,1例窒息,1例多器官功能衰竭.结论 吸毒会导致新生儿早产增加,窒息及NRDS的比例升高.妊娠晚期吸毒会导致新生儿戒断综合征.     

Screening for congenital adrenal hyperplasia: distribution of 17 alpha-hydroxyprogesterone concentrations in neonatal blood spot specimens

In a retrospective analysis of 24 cases of congenital adrenal hyperplasia (CAH) in neonates born in the province of Manitoba during the last 20 years, we set out to determine whether patients, in particular male infants with salt-losing CAH, were being missed by the usual forms of clinical ascertainment. Although the overall incidence of 1/14,500 live births was similar to that found in several screening surveys, a skewed female/male sex ratio of 2.2:1 suggested probable death among male infants with unrecognized adrenal insufficiency. These results led to a prospective analysis of 17 alpha-hydroxyprogesterone (17-OHP) levels in 1194 neonatal blood specimens by a solid-phase direct radioimmunoassay procedure to determine whether this method would be suitable for CAH screening. In 1103 neonates weighing greater than 2500 gm at birth, all 17-OHP values were less than 30 nmol/L (approximately 1000 ng/dl), with a mean of 8.2 nmol/L; values in male infants were slightly higher than in female infants. In 89 neonates with a birth weight less than 2500 gm, 17-OHP values were skewed, with nine having levels greater than 30 nmol/L and two greater than 50 nmol/L. Postnatal age (1 to 24 days) at the time of specimen collection had no effect on 17-OHP levels, although higher values occur during the first 24 hours. One unsuspected case of CAH in a male infant was discovered during the trial period. We conclude that neonatal CAH screening can permit diagnosis and therapy of affected male infants who are being missed by normal clinical evaluation. This radioimmunoassay method is relatively simple and inexpensive, and it has the specificity and sensitivity necessary to provide such mass screening.     

Cytomegalovirus infection in a neonatal intensive care unit. Blood transfusion practices and incidence of infection

We studied blood transfusion variables and cytomegalovirus (CMV) infection in 385 infants admitted to the Duke University Medical Center, Durham, NC, neonatal intensive care unit over 14 months. Cytomegalovirus antibody titers were measured at birth and monthly thereafter. Urine cultures for CMV were performed regularly. Infants admitted in the first six months (n = 197) received conventionally prepared blood. Infants admitted in the remaining eight months (n = 188) were given frozen, deglycerolized blood. Of the 105 infants weighing 1250 g or less (low birth weight [LBW]), 90 (86%) received transfusions. Two hundred eighty infants weighed more than 1250 g (non-LBW), and 111 (40%) of these were given blood. In the first six months of the study, three infants had CMV viruria. One case was congenital; two were acquired. Both infants who acquired infection were antibody-positive at birth and received multiple transfusions. In the remaining eight months, five infants had CMV viruria. Two cases were congenital; three were acquired. The three infants who acquired infection were antibody-positive at birth and received multiple transfusions. Our study demonstrates that infants with an LBW are more likely to receive blood transfusion and to be given significantly more blood than non-LBW infants. There was no difference in the number of infants acquiring CMV in the two periods despite the use of different preparations of blood.     

Nosocomial bacterial infections in very low birth weight infants

The occurrence of congenital and nosocomial bacterial septicaemia has been documented by identifying the number of positive blood cultures by reviewing the laboratory and clinical records of 394 very low birth weight infants who were consecutively admitted to a neonatal intensive care unit over a 40-month period. The incidence of congenital septicaemia was 6% and of nosocomial septicaemia 17%. The commonest causes of congenital infection wereStreptococcus agalactiae Staphylococcus epidermidis andEnterococcus faecalis (each in 18% of cases). The commonest cause of nosocomial infection wasS. epidermidis (51% of cases), except in infants of birth weight less than 750 g. Risk factors for nosocomial infection were extremely low birth weight, very preterm birth and prolonged ventilation. Nosocomial infection was associated with significantly lengthened hospital admission.     

Continuous hemodialysis therapy for an extremely low‐birthweight infant with hyperammonemia

Hyperammonemia of newborns should be treated promptly, and the outcome depends on the rapid elimination of excessive plasma ammonia. We encountered a case of transient hyperammonemia in an extremely low‐birthweight infant whose plasma ammonia decreased sufficiently after continuous hemodialysis therapy. It seems that continuous hemodialysis therapy using the peripheral artery and umbilical vein is useful for hyperammonemia of extremely low‐birthweight infants; however, there are several problems to consider due to the immaturity of these infants.     

Cobalamin C defect presenting as severe neonatal hyperammonemia

Cobalamin C (Cbl-C) defect is the most common inborn error of cobalamin metabolism which causes a block in the pathway responsible for the synthesis of its two metabolically active forms methyl- and adenosylcobalamin. Cbl-C defect causes the accumulation of methylmalonic acid and homocysteine and decreased methionine synthesis. The clinical presentation of patients with early-onset Cbl-C defect, characterized by a multisystem disease with severe neurological, ocular, hematological, renal, gastrointestinal, cardiac, and pulmonary manifestations, differs considerably from what observed in the “classical” form of methylmalonic aciduria caused by defect of methylmalonyl-CoA mutase. This last condition is in most cases dominated in the neonatal period by a metabolic encephalopathy “intoxication type” with severe hyperammonemia and ketoacidosis. We report a Cbl-C defect patient presenting a neonatal encephalopathy with severe hyperammonemia and ketoacidosis who was successfully treated with peritoneal dialysis. Conclusion: To the best of our knowledge, there are no reported cases of Cbl-C defect showing an acute presentation resembling a classical methylmalonic aciduria. This observation enlarges the spectrum of inherited diseases to be considered in the differential diagnosis of neonatal hyperammonemia.