一种新的线粒体DNA基因突变:线粒体脑肌病伴高乳酸血症和卒中样发作综合征1例基因与残障特征分析

背景线粒体脑肌病伴高乳酸血症和卒中样发作综合征(MELAS)是线粒体脑肌病中最常见的一种临床类型,多种线粒体基因突变均可导致MELAS.目的探讨1例MELAS患者的临床表现和线粒体基因突变的关系.设计临床、病理和基因分析对照研究.地点和对象实验在解放军济南军区总医院神经内科病房、神经病理实验室和神经分子生物学实验室进行.患者,男,13岁,因发作性头痛、呕吐,肢体抽搐1个月于2001-06-04入院,入院后逐渐出现失明和智能减退.血乳酸和丙酮酸水平升高,临床诊断MELAS.干预对患者行头颅MRI检查、脑活检病理检查和线粒体基因分析.主要观察指标临床表现特点、MRI病变特征、脑组织病理改变特点以及线粒体基因突变类型.结果患者不存在能引起MELAS的较常见的突变,但在线粒体3314～3589之间有276 bp的碱基缺失.结论线粒体DNA 3314～3589位点之间276 bp的碱基缺失可能是能够导致MELAS的一种新的基因突变类型,也是导致患者出现失明、癫痫和痴呆的原因.     

Metabolic acidosis not due to lactic acidosis in patients with severe acute asthma

Asthmatics seeking emergency care for severe acute asthma may show metabolic acidosis. We sought to determine the frequency of metabolic acidosis in such patients and to assess the relative contributions of renal bicarbonate loss and lactic acid accumulation to this acidosis. Twenty-two asthmatics (21-71 yr; four males, and 18 females) who came consecutively to the emergency department with severe acute asthma were studied. Most patients reported that their asthmatic symptoms had begun to worsen greater than or equal to 2 days before the emergency department visit. Within several hours, simultaneous measurements of arterial blood gases, whole blood lactate, and serum electrolytes were made. Ten of 22 patients were found to have metabolic acidosis (base deficit greater than 2 mEq/L). All ten patients had nonanion gap acidosis, while nine of ten had whole blood lactate values in the normal range (0.33 to 2.55 mmol/L). In the one patient with an elevated whole blood lactate level, the concentration of lactate in excess of normal (0.45 mmol/L) could not account for the magnitude of the base deficit (-4.9 mEq/L). We conclude that a) nonanion gap metabolic acidosis is very common in asthmatics with acute severe asthma (prevalence 45% in our series), and b) the mechanism of the base deficit in these patients is excessive renal bicarbonate excretion. We believe that the latter occurs as a renal compensatory response to a preceding period of hypocapnia due to hyperventilation related to worsening asthma.     

Zidovudine-associated type B lactic acidosis and hepatic steatosis in an HIV-infected patient

A 34-year-old obese woman with human immunodeficiency virus (HIV) infection diagnosed a year earlier was seen because of nausea, vomiting, and intermittent diarrhea for 3 weeks. Her current medications included zidovudine. Physical examination revealed tachypnea and tender hepatomegaly. Computed tomography of the abdomen showed hepatomegaly with fatty infiltration. Liver enzymes were within normal range except for elevated lactate dehydrogenase (LDH). The serum bicarbonate value was low, with a lactate level three times normal. The tachypnea and dyspnea worsened as lactate concentrations rapidly increased to 15 times normal. Although her Po2 and cardiac index were initially adequate, the patient had acute respiratory failure. She died with multiorgan dysfunction, including hepatic failure, severe lactic acidemia, disseminated intravascular coagulation, and renal failure. Autopsy revealed hepatomegaly and massive steatosis. Physicians should consider lactic acidosis in patients taking zidovudine and having unexplained tachypnea, dyspnea, and low serum bicarbonate concentrations.     

Outcome of severe lactic acidosis associated with metformin accumulation

Introduction  

Metformin associated lactic acidosis (MALA) may complicate metformin therapy, particularly if metformin accumulates due to renal dysfunction. Profound lactic acidosis (LA) generally predicts poor outcome. We aimed to determine if MALA differs in outcome from LA of other origin (LAOO).     

Cardiac tamponade: a new complication in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes

We report the first case of cardiac tamponade in a 14-year-old female patient with an underlying illness of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient underwent a subxiphoid pericardiocentesis and pericardiotomy smoothly and was discharged with no sequelae. The coexistence of massive pericardial effusion and MELAS has never been mentioned in any literature. This case report attempts to exemplify the possibility of this connection.     

利奈唑胺致肝功能异常及乳酸酸中毒1例

利奈唑胺是(嗯)唑烷酮类抗菌药物,该药对革兰阳性球菌的抗菌谱广,其耐受性良好,常见不良反应为恶心、呕吐等胃肠道反应;严重不良反应如总胆红素、尿素氮等可逆性升高者少见,常无需停药;最严重的不良反应有骨髓抑制(包括贫血、白细胞下降、血小板减少),周围神经病变和乳酸酸中毒[1].现就中国医科大学附属第一医院感染科近期诊治的1例利奈唑胺致肝功能异常及乳酸酸中毒,报道如下. 患者男,55岁.因咳嗽,咯黄痰,高热寒战1周,伴气急不适,活动后气急加重,在当地住院治疗.予以头孢拉定0.5g静脉滴注,每8小时1次,治疗1周后未见好转,病情逐渐加重.停用头孢拉定,改为头孢吡肟1 g静脉滴注,每12小时1次,治疗10d仍未见好转,遂于2011年3月7日转入中国医科大学附属第一医院感染科.患者自述既往健康,否认贫血、肝炎、肾炎等疾病史,无输血及家族溶血史.     

超声心动图提示线粒体脑肌病伴高乳酸血症和脑卒中样发作综合征早期心肌受损2例

病例1,男,21岁,无明显诱因出现持续性紧箍样头痛伴发作性口角抽搐1个月;既往神经性耳聋4个月.查体:神志清;双侧眼睑下垂,双侧眼球各方向运动受限;四肢肌力5级,肌张力正常,病理征均(一).实验室检查:血浆乳酸(lactic acid,Lac)24.1 mg/dl,血清肌钙蛋白Ⅰ(cardiac troponin Ⅰ,...     

MELAS型线粒体脑肌病的MRI诊断

目的 探讨MELAS型线粒体脑肌病的MRI的表现特点.方法 回顾分析10例经病理证实的MELAS型线粒体脑肌病患者的临床及MRI检查资料.结果 10例患者均为多脑叶发病,5例双侧颞、枕、顶叶皮层及皮层下可见大片状长T1长T2信号影,具有一定对称性,3例右侧额叶、颞叶、枕叶大片状长T1长T2信号影,2例左侧颞叶、枕叶大片状长T1长T2信号影,病变不按血管支配区分布.FLAIR序列呈高信号,急性期病变于DW1序列呈高信号,有3例累及脑深部核团,累及豆状核2例,累及豆状核和尾状核1例,累及小脑2例,累及脑干1例,并有不同程度脑萎缩4例.增强扫描少有强化.结论 MELAS型线粒体脑肌病的MRI表现有一定特征性,但最终诊断需结合临床表现和实验室检查.     

Pharmacokinetics and pharmacodynamics of dichloroacetate in children with lactic acidosis due to severe malaria

Lactic acidosis frequently complicates severe malaria in Africanchildren, and is a strong independent predictor of mortality.We tested the hypothesis that sodium dichloroacetate (DCA),an activator of pyruvate dehydrogenase, rapidly reduces hyperlactataemiain this patient population. Eighteen children with severe malariaand capillary plasma lactate 5     

以剧烈腹痛为表现的糖尿病乳酸酸中毒一例

糖尿病可引起很多种并发症,其中乳酸酸中毒(lactic acidosis,LA)极其少见,一旦发生,病情危重,病死率极高.现将1例以剧烈腹痛为表现的糖尿病LA报道如下. 患者男,71岁,主诉“腹泻2d,腹痛5h”.入院前2天出现腹泻,每日解稀水便20余次,每次量约50 mL,伴恶心、呕吐,未在意,未诊治.入院前5h出现剑突下剧烈性疼痛,无法忍受,伴胸闷、气短,就诊于县医院,给予“盐酸哌替啶”止痛治疗,效果不佳而来我院.查体:P130次/min,R 21次/min,BP 98/67 mmHg (1 mmHg=0.133 kPa),T 36.8℃.嗜睡,心律不齐,呈房颤心律,腹软,剑突下压痛,无反跳痛,肠鸣音活跃.既往史:6年前确诊为“2型糖尿病、糖尿病肾病、心房颤动、冠心病”.辅助检查:血糖15.38 mmoL/L,血常规WBC 21.5×109 L-1,肾功能BUN 16.4 mmol/L,CRE 308μmol/L,电解质K+6.6 mmol/L,TCO2 3.8 mL/L,尿常规隐血+蛋白+酮体+,血气分析pH 6.89,乳酸＜15 mmol/L.     

Hepatic fructose-1,6-diphosphatase deficiency: A cause of lactic acidosis and hypoglycemia in infancy

An 8-month-old female, maintained on breast feeding for 6 months, experienced numerous attacks of hyperventilation when weaned to baby food and was admitted with severe lactic acidosis (20 mM) and hypoglycemia. Physical examination was negative except for hepatomegaly. Fasting (18 hr) after stabilization on a high carbohydrate diet resulted in hypoglycemia (plasma glucose 40 mg/100 ml), lactic acidosis (6-10 mM), and a rise in plasma alanine. Glucagon produced a glycemic response after 6 hr, but not after 18 hr fasting. Intravenous galactose increased plasma glucose (Delta 45 mg/100 ml) but intravenous fructose, glycerol, and alanine caused a 40-50% fall in plasma glucose and a significant rise in lactate (Delta 3-4 mM).Liver biopsy showed fatty infiltration. Liver slices incubated with galactose, lactate, fructose, alanine, or glycerol converted only galactose to glucose. Hepatic glycolytic intermediates were increased below the level of fructose-1,6-diphosphate and decreased above. Hepatic phosphorylase, glucose-6-phosphatase, amylo-1,6-glucosidase, phosphofructokinase, fructose-1-phosphate aldolase, and fructose-1,6-diphosphate aldolase levels were normal, but no fructose-1,6-diphosphatase (FDPase) activity was detected. Further studies on the liver homogenate of this patient revealed the presence of an acid-precipitable activator of FDPase.Normal plasma glucose and lactate levels were maintained on an 800 cal diet of 66% carbohydrate (sucrose and fructose excluded). 5% protein, and 20% fat. When carbohydrate was reduced to 35% and protein or fat increased to 23 and 53% respectively, lactic acidosis and hypoglycemia recurred. These studies show that a deficiency of FDPase produced infantile lactic acidosis and hypoglycemia and can be controlled by an appropriate diet.     

Familial mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episode syndrome: Three case reports

BACKGROUNDMitochondrial encephalomyopathy (ME) is a multisystem metabolic disease that primarily affects the central nervous system and skeletal muscle. It is caused by mutations in mitochondrial or nuclear DNA, resulting in abnormal mitochondrial structure and function and insufficient ATP synthesis. The most common subtype is mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome. In recent years, reports of MELAS syndrome have increased but familial cases are rare.CASE SUMMARYWe report a case of familial MELAS syndrome. Cases 2 and 3 are sisters and case 1 is their nephew. All are short in stature and showed stroke-like episodes with rapid onset and no obvious symptoms such as paroxysmal headache, aphasia, or blurred vision. After admission, blood lactate levels were significantly higher than normal. The patients underwent magnetic resonance imaging of the head. Cases 1 and 2 were considered to have ME, whereas case 3 was considered to have a space-occupying lesion in the left temporal lobe. Pathological evaluation showed no obvious tumor cells in the brain lesions of case 3. Muscle biopsy or genetic test results were consistent with ME. The patients were diagnosed with MELAS syndrome and their symptoms improved with intravenous infusions of coenzyme Q10, coenzyme A, vitamin B, and vitamin C. At the 6 mo follow-up, there was no recurrence or progression.CONCLUSIONWhen a patient has MELAS syndrome, familial MELAS syndrome should be considered if related family members have similar symptoms.