5-Fluorouracil-Induced Hyperammonemia Encephalopathy in a Patient with Gastric Cancer

Chemotherapy with 5-fluorouracil (5 FU) has been widely used to treat advanced gastric cancer. Knowing the side effects is therefore important in order to better prevent them. Fluoropyrimidine-induced hyperammonemic encephalopathy is a rare complication and characterized neurological status with elevated ammonia level without radiological abnormalities. We report the first case of 5 FU-induced hyperammonemic encephalopathy in women patients on induction chemotherapy for gastric cancer in Madagascar. His ammonia level (NH3) was 102 μmol/l. The patient recovered from his confusional state after two days of treatment with hyperhydration and vitamin therapy.

Novel therapy for non-cirrhotic hyperammonemia due to a spontaneous splenorenal shunt

Spontaneous splenorenal shunts in the absence of cirrhosis have rarely been reported as a cause hyperammonemia with encephalopathy. Several closure techniques of such lesions have been described. Here we report a case of a patient with no history of liver disease who developed significant confusion. After an extensive workup, he was found to have hyperammonemia and encephalopathy due to formation of a spontaneous splenorenal shunt. There was no evidence of cirrhosis on biopsy or imaging and no portal hypertension when directly measured. The shunt was 18 mm and too large for embolization so the segment of the splenic vein between the portal vein and the shunt was occluded using an Amplatzer plug. Thus, the superior mesenteric flow was directed entirely to the liver. After interventional radiology closure of the shunt using this technique there was complete resolution of symptoms.The case represents the first report of a successful closure of splenorenal shunt via percutaneous embolization of the splenic vein with an amplatzer plug using a common femoral vein approach.

Hyperammonemia,brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication

AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats were divided into four groups.Group Ⅰ:sham operation;Ⅱ:Prehepatic portal hypertension,produced by partial portal vein ligation;Ⅲ: Acetaminophen intoxication and Ⅳ:Prehepatic portal hypertension plus acetaminophen.Acetaminophen was administered to produce acute hepatic injury.Portal pressure,liver serum enzymes and ammonia plasma levels were determined.Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity.Reflexes and behavioral tests were recorded. RESULTS:Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ.Uver enzymes and ammonia plasma levels were increased in groups Ⅱ,Ⅲ and Ⅳ.Prehepatic portal hypertension (group Ⅱ),acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia.Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ.Behavioral test (rota rod) was altered in group Ⅳ. CONCLUSION:These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (oltotoxic).Group Ⅳ,with behavioral altered test,can be considered as a model for study at an early stage of portal-systemic encephalopathy.

Hyperammonemia crisis following parturition in a female patient with ornithine transcarbamylase deficiency

Ornithine transcarbamylase deficiency(OTCD) is an X-linked disorder,with an estimated prevalence of 1 per 80000 live births.Female patients with OTCD develop metabolic crises that are easily provoked by non-predictable common disorders,such as genetic(private mutations and lyonization) and external factors;however,the outcomes of these conditions may differ.We resuscitated a female patient with OTCD from hyperammonemic crisis after she gave birth.Hyperammonemia after parturition in a female patient with OTCD can be fatal,and this type of hyperammonemia persists for an extended period of time.Here,we describe the cause and treatment of hyperammonemia in a female patient with OTCD after parturition.Once hyperammonemia crisis occurs after giving birth,it is difficult to improve the metabolic state.Therefore,it is important to perform an early intervention before hyperammonemia occurs in patients with OTCD or in carriers after parturition.

Hyperammonemia-induced encephalopathy: A rare devastating complication of bariatric surgery

The clinical manifestations of hyperammonemia are usually easily identifiable to the clinician when associated with liver disease and lead to prompt diagnosis and treatment. However, hyperammonemia-induced encephalopathy is rare in adults in the absence of overt liver disease, thus diagnosis is often delayed or missed leading to potentially life threatening complications. Without proper treatment, such patients can decompensate rapidly with poor outcomes including seizures, coma, and death. Early assessment of plasma ammonia levels in patients with normal hepatic function and characteristic symptoms of encephalopathy can lead to early intervention while investigating the underlying etiology. We describe a patient who presented with a 2-year progression of waxing and waning acute mental status changes after a Roux-en-Y gastric bypass surgery. He was found to have elevated ammonia level as well as orotic aciduria; results consistent with a urea cycle disorder. After consulting neurology as well as toxicology, he ultimately improved after dietary protein restriction, sodium benzoate and lactulose therapy. While rare, clinicians should have a high index of suspicion for late onset urea cycle disorders in symptomatic patients presenting with encephalopathy secondary to hyperammonemia.

Hyperammonemia induced oxidative stress in cirrhotic rats without promoting differential protein expression in the brain cortex: A 2D-DIGE analysis

Oxidative stress induced by a high ammonia concentration could modify protein expression in the brain. This study was undertaken in order to investigate the impact of hyperammonemia, caused by thioacetmide (TAA) in rats, on brain cortex protein expression using 2D-DIGE, and analyzing its role in the pathogenesis of HE. Hyperammonemia was induced with TAA. Ammonia and active oxidants were measured by L-glutamate dehydrogenase and dichlorodihydrofluorescein diacetate methods, respectively. Lipid peroxidation and protein oxidation biomarkers were also studied. Differential protein expression in the cortex of TAA- and control-rats was studied by 2D-DIGE. Image analysis was performed using the DeCyder? Software. Ammonia concentration in plasma and brain tissue was higher in TAA-rats compared to control-rats, 3.12 and 2.43 fold higher, respectively. Active oxidants production in TAA-rats was increased by 2.7 fold compared to control-rats. Measurements of MDA, HNE and carbonyl groups, biomarkers of lipid peroxidation and protein oxidation respectively, were found to be statistically significantly increased in TAA-rats compared to control-rats (3.16-, 2.44- and 1.95-fold, respectively), reflecting the presence of oxidative stress in the brain of TAA-rats. 2D-DIGE analysis of brain cortex protein allowed the detection of 2896 spots, however, image analysis showed no statistically significant differential protein expression between the proteins expressed in TAA- and control-rats. No statistical significant differential protein expression in the cortex of TAA-rats was observed, although oxidative stress biomarkers for lipid and proteins were higher in the brain of TAA-rats than in control-rats. These results support the idea that oxidative post-translational modifications are implicated in HE physiopathology.

Relationship between the incidence of non-hepatic hyperammonemia and the prognosis of patients in the intensive care unit

BACKGROUND Ammonia is a normal constituent of body fluids and is found mainly through the formation of urea in the liver.Blood levels of ammonia must remain low as even slightly elevated concentrations(hyperammonemia)are toxic to the central nervous system.AIM To examine the relationship between the incidence of non-hepatic hyperammonemia(NHH)and the prognosis of patients who were admitted to the intensive care unit(ICU).METHODS This is a prospective,observational and single-center study.A total of 364 patients who were admitted to the ICU from November 2019 to February 2020 were initially enrolled.Changes in the levels of blood ammonia at the time of ICU admission and after ICU admission were continuously monitored.In addition,factors influencing the prognosis of NHH patients were analyzed.RESULTS A total of 204 patients who met the inclusion criteria were enrolled in this study,including 155 NHH patients and 44 severe-NHH patients.The incidence of NHH and severe-NHH was 75.98% and 21.57%,respectively.Patients with severe-NHH exhibited longer length of ICU stay and higher Acute Physiologic Assessment and Chronic Health Evaluation and Sequential Organ Failure Assessment scores compared to those with mild-NHH and non-NHH.Glasgow Coma Scale scores of patients with severe-NHH were than those of non-NHH patients.In addition,the mean and initial levels of ammonia in the blood might be helpful in predicting the prognosis of NHH.CONCLUSION High blood ammonia level is frequent among NHH patients admitted to the ICU,which is related to the clinical characteristics of patients.Furthermore,the level of blood ammonia may be helpful for prognosis prediction.

苯丁酸甘油酯治疗儿童鸟氨酸氨甲酰基转移酶缺乏症1例

苯丁酸甘油酯(glyceryl phenylbutyrate,GPB)是治疗鸟氨酸氨甲酰基转移酶缺乏症(ornithine transcarbamylase deficiency,OTCD)的长期管理药物,可有效控制高氨血症,但国内使用该药的经验匮乏。该文回顾性分析上海交通大学医学院附属上海儿童医学中心1例诊断为OTCD的患儿资料,并进行相关文献复习。该患儿确诊后使用GPB治疗,随后进行疗效随访和药学监测。患儿,男,6岁6个月,语言发育差,不听指令,脾气暴躁并伴有攻击性行为。监测血氨最高327μmol/L;尿有机酸分析提示尿嘧啶水平升高;头颅磁共振成像示双侧大脑半球广泛异常信号;基因检测发现OTC基因新生突变(c.241T>C,p.S81P)。予以GPB治疗后1、2、3个月左右的血氨分别为43、80、56μmol/L。患儿治疗期间血氨控制良好,未见与药物相关的不良反应,发育落后情况较前改善,可听指令,脾气好转,无攻击性行为。

腹膜透析桥接连续性肾脏替代治疗高氨血症、肝功能衰竭及脓毒症新生儿1例报告

1病例资料患儿男,因“出生后4 d,反应差1 d,新生儿高氨血症”于2021年12月2日收入我院。2021年11月28日,患儿于胎龄39+1周在当地医院经剖宫产出生。否认脐带、胎盘、羊水异常,否认宫内窘迫,否认窒息史,Apgar评分10-10-10。

以痫性发作为表现成人起病的瓜氨酸血症Ⅱ型1例

对SLC25A13基因纯合变异引起以痫性发作为表现的成人起病的瓜氨酸血症Ⅱ型(adult-onset typeⅡcitrullinemia,CTLN2)1例进行回顾性分析。患者,男,28岁,反复四肢抽搐4年余,再发加重2个月,平素喜食花生及肉类。头颅MRI检查未见异常,予抗癫痫治疗效果不佳,进一步查血转氨酶、血氨和瓜氨酸升高,基因检测显示SLC25A13基因c.851_854del纯合致病突变,诊断为CTLN2,予高蛋白、高脂肪、低糖饮食和精氨酸治疗,随访半年无痫性发作。对反复痫性发作伴有特殊饮食嗜好者应注意CTLN2可能,基因检测对CTLN2的诊断具有重要作用,可为临床诊治提供依据。

新生儿高氨血症11例临床及基因变异分析

目的分析11例新生儿高氨血症患儿临床特征、基因变异情况和病因。方法回顾性分析2016年7月至2022年8月新乡医学院第一附属医院新生儿科及甘肃省妇幼保健院收治的11例新生儿期发病的高氨血症患儿临床资料、实验室检查及基因检测结果,并对其中2例再生育家系进行产前基因诊断。结果11例患儿均表现为反应差,尚有惊厥、意识障碍及呕吐。5例患儿为OTC基因变异所致鸟氨酸氨甲酰基转移酶缺乏症(OTCD),分别为大片段缺失变异、错义变异及剪切变异;4例患儿为CPS1基因变异所致氨基甲酰磷酸合成酶1缺乏症(CPS1D),分别为无义变异、错义变异及剪切变异;1例为ASS1基因变异所致的瓜氨酸血症Ⅰ型(CTLN1),为错义变异;1例为基因检测阴性的新生儿暂时性高氨血症(THAN)。结论对临床新生儿高氨血症需警惕遗传性疾病可能,及时基因检测可明确诊断,积极给予血液净化和肝移植治疗可改善神经发育预后。

Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat

Evidence suggests that the hyperammonemia （HA）-induced neuroinflammation and alterations in the serotonin （5-HT） system may contribute to cognitive decline and anxiety disorder during hepatic encephalopathy （HE）. Probiotics that maintain immune system homeostasis and regulate the 5-HT system may be potential treatment for HA-mediated neurological disorders in HE. In this study, we tested the efficacy of probiotic Lactobacillus helveticus strain NS8 in preventing cognitive decline and anxie- ty-like behavior in HA rats. Chronic HA was induced by intraperitoneal injection of ammonium acetate for four weeks in male Sprague-Dawley rats. HA rats were then given Lactobacillus helveticus strain NS8 （109 CFU mL 1） in drinking water as a dai- ly supplementation. The Morris water maze task assessed cognitive function, and the elevated plus maze test evaluated anxie- ty-like behavior. Neuroinflammation was assessed by measuring the inflammatory markers： inducible nitric oxide synthase, prostaglandin E2, and interleukin-1 13 in the brain. 5-HT system activity was evaluated by measuring 5-HT and its metabolite, 5-HIAA, and the 5-HT precursor, tryptophan. Probiotic treatment of HA rats significantly reduced the level of inflammatory markers, decreased 5-HT metabolism, restored cognitive function and improved anxiety-like behavior. These results indicate that probiotic L. helveticus strain NS8 is beneficial for the treatment of cognitive decline and anxiety-like behavior in HA rats.

OTC基因新变异致鸟氨酸氨甲酰基转移酶缺陷病1例报告

目的报告1例鸟氨酸氨甲酰基转移酶缺陷病(ornithine transcarbamylase deficiency,OTCD)患儿的临床及分子遗传学特点,为本病诊疗提供参考。方法回顾性分析一例OTCD患儿临床和实验室资料。结果患儿女性,1岁6月,因“反复呕吐伴烦躁不安4月余”就诊。查体发现双下肢张力减退,双侧膝关节反射亢进,双侧踝阵挛阳性。血生化谷丙转氨酶、谷草转氨酶及血氨升高,尿液有机酸分析显示尿嘧啶、乳清酸和4-羟基苯乳酸水平升高。遗传学分析在患儿OTC基因检出c.612614del(p.Ile204del)新生变异,结合ACMG标准判断该变异具有致病性。经限制蛋白质摄入、精氨酸、瓜氨酸和苯甲酸钠等治疗后患儿病情控制仍不理想,于2岁时进行肝移植治疗,移植后患儿肝功能和血氨恢复正常。结论本文通过临床和遗传学研究,发现1个OTC新变异c.612614del,确诊了一例OTCD患儿,为本病确诊和遗传咨询提供了遗传学标记物,同时为临床和实验室特征的科学认识积累了资料。

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。

Treatment of portosystemic shunt-borne hepatic encephalopathy in a 97-year-old woman using balloon-occluded retrograde transvenous obliteration:A case report

BACKGROUND Hyperammonemia and hepatic encephalopathy are common in patients with portosystemic shunts.Surgical shunt occlusion has been standard treatment,although recently the less invasive balloon-occluded retrograde transvenous obliteration(B-RTO)has gained increasing attention.Thus far,there have been no reports on the treatment of portosystemic shunts with B-RTO in patients aged over 90 years.In this study,we present a case of hepatic encephalopathy caused by shunting of the left common iliac and inferior mesenteric veins,successfully treated with B-RTO.CASE SUMMARY A 97-year-old woman with no history of liver disease was admitted to our hospital because of disturbance of consciousness.She had no jaundice,spider angioma,palmar erythema,hepatosplenomegaly,or asterixis.Her blood tests showed hyperammonemia,and abdominal contrast-enhanced computed tomography revealed a portosystemic shunt running between the left common iliac vein and the inferior mesenteric vein.She was diagnosed with hepatic encephalopathy secondary to a portosystemic shunt.The patient did not improve with conservative treatment:Lactulose,rifaximin,and a low-protein diet.B-RTO was performed,which resulted in shunt closure and improvement in hyperammonemia and disturbance of consciousness.Moreover,there was no abdominal pain or elevated levels of liver enzymes due to complications.The patient was discharged without further consciousness disturbance.CONCLUSION Portosystemic shunt-borne hepatic encephalopathy must be considered in the differential diagnosis for consciousness disturbance,including abnormal behavior and speech.

重视新生儿高氨血症

新生儿高氨血症病因复杂、进展迅速,如漏诊或血氨控制不及时,会导致患儿生命危险或预后不良。但由于新生儿高氨血症临床表现缺乏特异性,加之临床医师认识不足,常导致误诊或漏诊。现对新生儿高氨血症诊治中的临床问题进行总结和讨论,以引起临床医师的重视,提高诊疗水平,降低致残率及病死率。

4例连续肾脏替代治疗新生儿遗传代谢疾病合并高氨血症的救治与护理

总结4例持续肾脏替代治疗新生儿遗传代谢疾病合并高氨血症的救治与护理经验,包括环境及用物的准备、建立动静脉血管通路、连续肾脏替代治疗与管理、密切监测体温、做好镇痛镇静治疗、严密观察出血情况等。通过专业的护理措施保证了4例患儿连续肾脏替代治疗效果。

鸟氨酸氨甲酰基转移酶缺乏症3例报告

鸟氨酸氨甲酰基转移酶缺乏症属于尿素循环障碍疾病中最常见的类型,临床表现主要为高氨血症及神经系统损害。临床表现严重程度与酶活性的缺失程度及血氨水平有关,轻症可表现为呕吐、惊厥、意识障碍等,重症则可出现脑疝甚至死亡。早期诊断和积极治疗,可改善预后。本文分析3例山东大学附属儿童医院重症医学科诊断的鸟氨酸氨甲酰基转移酶缺乏症患儿的临床表现、实验室检查、治疗及转归情况,以利于临床医生加深对本病的认识,提高诊断、治疗成功率。

血氨及胆碱酯酶对肝硬化伴轻微肝性脑病的早期诊断价值

目的 探讨血清标志物对肝硬化合并轻微型肝性脑病(MHE)的早期诊断价值。方法 前瞻性纳入2020年4月—2022年2月于宁夏医科大学总医院住院治疗,并经临床表现、实验室检查、影像学检查或肝穿刺活检确诊为乙型肝炎肝硬化患者81例。根据数字连接试验A(NCT-A)和数字符号试验(DST)分为单纯肝硬化组45例、MHE组36例。检测肝功能(ALT、AST、GGT、ALP和TBil)、白蛋白、血氨、胆碱酯酶和凝血酶原时间。计数资料2组间比较采用χ^(2)检验;正态分布的计量资料2组间比较采用独立样本t检验;非正态分布的计量资料2组间比较采用Mann-Whitney U检验,多组间比较采用Kruskal-Wallis H检验。使用Logistic回归和受试者工作特征曲线下面积(AUC)分析MHE的预测因素。结果 与单纯肝硬化组相比,MHE组NCT-A量表评分升高(Z=-7.110,P<0.001),DST量表评分降低(t=12.223,P<0.001),差异均有统计学意义。单因素分析显示,AST、白蛋白、凝血酶原时间、胆碱酯酶和血氨在MHE患者中显著改变(Z值分别为-2.319、-2.643、-1.982、-6.594、-5.331,P值均<0.05);但在多变量分析中,只有胆碱酯酶和血氨水平是显著的预测因子(P值均<0.05),并且它们与Child-Pugh评分分级相关(P值均<0.05)。胆碱酯酶、血氨以及两者联合诊断MHE的AUC值分别为0.925、0.845和0.941,最佳截断值分别为2966、60和0.513。结论 血氨、胆碱酯酶及两者联合检测对肝硬化合并MHE的早期诊断具有潜在的临床价值。

新生儿高氨血症多中心现状调查及临床分析

目的通过回顾性多中心现状调查,了解新生儿高氨血症的发病率、病因分类、临床特征及预后情况。方法以2017年1月—2022年11月28家参与单位分娩并入住新生儿科治疗的血氨>100μmol/L的新生儿作为研究对象,用描述性研究方法对确诊高氨血症新生儿的发病率、病因分类、临床特征、基因表型及预后随访等情况进行分析总结。结果观察期间28家单位总分娩量708421例,73例符合新生儿高氨血症诊断标准,其中男44例、女29例。病因分类中先天遗传性高氨血症32.88%(24例),暂时性高氨血症15.07%(11例),继发性高氨血症16.44%(12例),另有26例原因不明(35.61%)。主要临床表现有反应差、气促、喂养困难、抽搐、意识障碍等。主要异常实验室检查为代谢性酸中毒、血乳酸增高、低血糖、电解质紊乱,血氨基酸和/或尿氨基酸异常,13例进行了基因检查的患儿中11例发现异常。治疗上除常规对症支持治疗外,主要采用了精氨酸排氨(21例)、补充肉碱(8例)、血液净化(9例)以及腹膜透析(3例)。预后方面,24例先天遗传性高氨血症患儿死亡10例,放弃治疗6例,好转出院8例;12例继发性高氨血症患儿死亡1例,放弃治疗3例,预后不详1例,治愈出院7例;11例暂时性高氨血症患儿均治愈或好转出院;而26例不明原因高氨血症病例死亡17例,放弃治疗4例,预后不详3例,好转出院2例。结论新生儿高氨血症发病率不高,但病情进展快,病死率高,尤其是先天性遗传高氨血症和不明原因高氨血症病例。提高临床医师对该病的认识,尽量做到早诊断,早治疗,可减少死亡及严重并发症。加强产前咨询,建立新生儿高氨血症筛查体系和新生儿高氨血症注册登记系统,具有积极的临床意义。