3例非典型异戊酸尿症患儿临床及基因型研究

目的探讨迟发型非典型异戊酸尿症患儿的临床、治疗及IVD基因突变特点。方法 3例非典型异戊酸尿症患儿,经尿液有机酸、血液酯酰肉碱谱分析发现异戊酸尿症,并经IVD基因突变检测确诊。患儿给予左卡尼汀、甘氨酸补充治疗及限亮氨酸饮食干预并进行随访。结果 3例患儿于1~2岁间发病,有不明原因呕吐、嗜睡,伴汗脚样体臭及代谢性酸中毒。3例患儿智力正常,均伴随显著的白细胞减少症,其中1例伴红细胞减少症。3例患儿血液异戊酰肉碱水平显著增高(4.6~8.2μmol/L),尿液异戊酰甘氨酸水平显著增高(36.1~1 783.56 mmol/mmol肌酐)。3例患儿IVD基因共检出6种突变,其中已知突变4种(c.157CT,c.214 GA,c.1183CG,c.1208AG),新突变2种(c.1039GA,c.1076AG)。经治疗后患儿顺利康复,目前1岁7个月~14岁,智力、运动及体格发育正常。结论迟发性异戊酸尿症临床表现复杂,于婴幼儿期发病,可有反复呕吐、酸中毒,通过血液酰基肉碱谱、尿液有机酸分析及基因分析确诊,左卡尼汀及饮食干预,疗效显著。     

新生儿异戊酸血症一例

患儿女,生后8d,因鼻塞伴奶量减少1d入院。患儿系第6胎第2产,胎龄41周,顺产,出生体重3000g,无窒息史,母乳喂养,吸吮有力。否认家族遗传病史。母亲曾人工流产4次,患儿胞兄生后7d因抽搐、昏迷在当地医院死亡,当时诊断VitK缺乏颅内出血。患儿无发热,无咳嗽、气促,无呕吐、腹泻,无尖叫、抽搐等。入院查体:生命体征平稳,反应可,全身轻度汗脚臭味,原始反射存在,四肢肌张力正常。入院诊断:上呼吸道感染。入院予以抗感染、对症治疗,静脉输注6%小儿氨基酸30ml+5%葡萄糖。治疗5h,患儿突然出现双上肢抽动,持续3min自行缓解,但反复发作,神志由淡漠到浅昏迷,无大汗、发热等。查体:P136次/mi     

HIBCH基因变异致3-羟基异丁酰辅酶A水解酶缺乏症一例并文献复习

目的探讨3-羟基异丁酰辅酶A水解酶(3-hydroxyisobutyryl-CoA hydrolase, HIBCH)缺乏症的临床特征并进行文献复习。方法回顾性研究1例HIBCH缺乏症患儿的临床资料, 并总结该病例的临床特点。以"3-羟基异丁酰辅酶A水解酶"以及"HIBCH"、"3-hydroxyisobutyryl-CoA hydrolase deficiency"为检索词检索中国知网、万方数据库、中华医学期刊全文数据库及PubMed数据库自建库至2023年10月的相关文献, 结合该例总结HIBCH缺乏症的临床特征、诊疗及预后。结果患儿, 男, 7月龄, 因"精神运动发育迟缓4个月伴倒退1个月"就诊。患儿先后出现喂养困难、精神运动发育迟缓及运动倒退等表现。血3-羟基丁酰肉碱升高、全外显子组测序发现HIBCH基因复c.365A>G(p.Y122C和外显子与缺失复合杂合变变异), 明确诊断HIBCH缺乏症。予以鸡尾酒疗法及低蛋白、高碳水化合物饮食及对症支持治疗后, 症状未见明显改善, 肌张力障碍加重, 手足徐动, 复查血3-羟基丁酰肉碱仍轻度增高, 头部磁共振显示双侧基底节对称性病...     

短链酰基辅酶A 脱氢酶缺乏症患儿临床特点及基因变异分析

目的探讨新生儿短链酰基辅酶A脱氢酶缺乏症(SCADD)基因型与表型的关系。方法回顾分析2015年至2018年,在青岛地区296 627例新生儿中筛查发现的7例SCADD患儿的临床资料。结果研究期间初次筛查可疑阳性人数为4 864例,初筛阳性率为0.16%;经基因检测确诊7例SCADD患儿,确诊阳性率为1/42375。7例患儿中,男性4例、女性3例,基因检测发现5种已知变异、4种未知变异,分别为c.1029+89_90insC、c.1031AG、c.1157GA、c.164CT和c.989GA,c.1130CT、c.1186GA、c.445AT和c.949AG。结论 SCADD基因型与血尿串联质谱筛查结果一致,但与临床表型关系不明确,早期诊断和治疗有助改善预后。     

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。     

新生儿高氨血症247例临床分析

目的 探讨新生儿高氨血症的病因、临床表现、干预措施和预后。方法 2016年4月至2020年12月,联勤保障部队第九八〇医院儿科收治高氨血症新生儿247例,回顾性分析患儿的临床资料。根据血氨水平分为重度组14例(≥200 μmol/L)、中度组110例(100～200 μmol/L)、轻度组123例(50～99 μmol/L)3组。比较各组的临床症状、治疗及预后情况。统计学方法采用χ²检验。结果 重、中、轻度组早产儿的比例分别为21.4%(3/14)、48.2%(53/110)、47.2%(58/123),差异无统计学意义(χ²=3.675,P=0.159)。重、中、轻度组患儿出现临床症状的比例分别为92.8%(13/14)、29.1%(32/110)、3.2%(4/123),重度组高于中度组和轻度组(χ²值分别为21.842、92.852,P<0.001),中度组高于轻度组(χ²=29.678,P<0.001)。247例患儿中,进行代谢病筛查173例(70.0%),确诊遗传代谢病12例;...     

小儿晕厥与代谢异常

晕厥是儿科常见急症,代谢异常所致的晕厥是儿童晕厥鉴别诊断的重要原因之一.导致儿童晕厥的代谢异常主要有低血糖、过度换气、电解质紊乱、低氧血症等,其中低血糖病因包括高胰岛素血症、垂体和肾上腺疾病、糖尿病、酮症性低血糖及糖和有机酸、氨基酸代谢缺陷病等.本文介绍导致儿童晕厥常见的代谢异常及病因、疾病诊断和治疗.     

丙酸血症两家系的临床特征及基因突变分析

目的：探讨2例丙酸血症患儿的临床特征及基因突变特点。方法回顾性分析2例丙酸血症患儿的病例资料及家系的基因突变检测,并复习相关文献,分析本病的临床表现、生化检测和基因突变特点。结果例1患儿,男,11 d,因“呕吐、气促”3 d 入院,新生儿期发病,入院后遗传代谢病筛查发现丙酰肉碱增高,丙酰肉碱／乙酰肉碱增高,尿有机酸分析发现甲基枸橼酸、甲基巴豆酰甘氨酸、3-羟基丙酸增高,诊断为丙酸血症,治疗过程中表现为反复感染,骨髓抑制,生物素治疗有效,随访过程中发现丙酰基肉碱水平较高,高甘氨酸血症,限制异亮氨酸、缬氨酸、蛋氨酸和苏氨酸饮食后丙酰基肉碱下降的同时易发生支链氨基酸的缺乏;虽然积极治疗仍表现明显的精神运动发育落后;基因检测患儿PCCB c．1301C＞T p．（Ala434Val）纯合突变,父母为PCCB c．1301C＞T p.（Ala434Val）杂合突变。例2患儿,女,7个月,因“呕吐伴代谢性酸中毒”入院。婴儿期发病,入院经检测诊断丙酸血症。患儿表现较例1患儿轻微,无反复感染,无骨髓抑制。随访过程中发现丙酰基肉碱水平较例1患儿明显偏低,有高甘氨酸血症,限制异亮氨酸、缬氨酸、蛋氨酸和苏氨酸饮食后丙酰基肉碱下降的同时不易发生支链氨基酸的缺乏;运动发育正常,精神及语言发育稍落后,检测到 PCCB 基因的一个纯合突变：c．167＿179del13insC p.（Asp56＿Lys60delinsAla）,其父亲、母亲各检测到一个杂合突变。结论2例丙酸血症患儿中,新生儿期发病、反复感染、骨髓抑制、高丙酰基肉碱水平,饮食控制中易发生支链氨基酸的缺乏,提示病情预后不佳,容易发生精神运动发育落后;目前报道2例（含本例）基因突变为 PCCB c.1301C＞T p．（Ala434Val）纯合突变,均病情严重。     

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。     

新生儿体重不增、反复代谢性碱中毒、低钾血症

患儿,女,出生胎龄29~(+2)周、体重1 210 g,因气促于生后10 min入院。入院后出现高血糖、多尿、体重不增等表现,伴有氮质血症,低氯性代谢性碱中毒,低钾、低钠血症,以及醛固酮、肾素、血管紧张素Ⅱ均升高,SLC12A1基因突变,确诊为新生儿巴特综合征。予补钠、补钾对症治疗,随访至生后8个月,神经、精神发育水平与纠正月龄基本相符,仍有轻度代谢性碱中毒,电解质基本正常。对于新生儿难以解释的多尿、电解质紊乱,应注意检测醛固酮、肾素、血管紧张素及基因筛查,发现SLC12A1基因突变可确诊。     

Isolation of adenovirus type 11 from the brain of a neonate with pneumonia and encephalitis

We describe a fatal case of adenovirus pneumonia accompanied by encephalitis in a neonate who showed lethargy on the 6th day and died on the 12th day. Adenoviral particles as well as viral intranuclear inclusions were noted in pulmonary alveolar epithelium cells. Neuropathological examination revealed diffuse oedema, perivascular cuffing and gliosis in the white matter. Adenovirus type 11 was isolated from lung, hilar lymph node, and brain tissue. This is the first instance of adenovirus isolation from brain tissue in a newborn infant. The viro-logical and neuropathological findings sugest the invasion of neural tissue by adenovirus and substantiate the significance of neurological symptoms observed in neonatal adenovirus infection.     

Management of acute metabolic decompensation in maple syrup urine disease: A multi-center study

BACKGROUND: Therapeutic modalities in acute metabolic decompensation in maple syrup urine disease (MSUD) are variable, and outcomes of each therapeutic measure have been known only individually. Factors that affect neurological outcome are not clear. METHODS: A questionnaire was sent throughout Japan to each pediatrician treating any of the 42 MSUD patients. RESULTS: Necessary information was available for 13 patients through the questionnaire, and through a publication for one patient. In nine of the 14 patients episodes of metabolic decompensation developed in the neonatal period. In the other five, the onset of disease was delayed until infancy or later. In the nine patients with neonatal onset, a pretreatment level of plasma leucine greater than 40 mg/100 mL or a duration of altered level of alertness longer than 10 days was associated with a poor neurological outcome. The therapeutic measures employed included intravenous infusion of glucose and electrolyte solution or hypertonic glucose and electrolyte solution, exchange transfusion, peritoneal dialysis, a large dose of thiamine and intravenous hyperalimentation. All patients had survived the episodes and were alive at the time of the survey. Five of the nine patients with neonatal onset have developed neurological sequelae to varying degrees. Episodes of metabolic decompensation in infancy or thereafter did not affect, or only minimally affected, the neurological outcome. CONCLUSION: Therapeutic goals to improve neurological outcome are to shorten the duration of the altered level of consciousness, and to minimize the peak plasma leucine level as much as possible.     

The contribution of protein catabolism to metabolic decompensation in 3-hydroxy-3-methylglutaric aciduria

Leucine and protein metabolism were studied using stable isotope techniques in 6-year-old twins with 3-hydroxy-3-methylglutaric aciduria during acute metabolic decompensation. The decompensation was preceded by prolonged fasting in twin 1 and by an upper respiratory infection in twin 2. Twin 2 was also studied when well (control study). During infection, leucine oxidation (36 mol/kg per hour), protein catabolism (6.0 g/kg per day) and urinary excretion of major leucine metabolites (104 mol/kg per hour) were all increased compared with the control study (16 mol/kg per hour, 4.7 g/kg per day and 28 mol/kg per hour respectively). During fasting, leucine oxidation (18 mol/kg per hour) was unchanged and protein catabolism (4.1 g/kg per day) was decreased despite substantially increased urinary metabolite excretion (87 mol/kg per hour) compared with the control study. These results indicate that protein mobilisation and leucine oxidation played important roles in metabolic decompensation during infection but not during fasting. It is likely that the increased metabolite excretion during fasting arose primarily from fatty acid catabolism, indicating the importance of this substrate in metabolic decompensation in 3-hydroxy-3-methylglutaric aciduria.     

Mediastinal teratoma in a neonate

A neonate with severe respiratory distress due to a benign mediastinal teratoma (MT) is reported. Despite early and easy surgical excision of the tumor, the child died due to poor cardiac function. Only ten cases of MT in neonates have been reported in the literature so far. While the tumor has been known to interfere with lung development in utero, postnatal myocardial dysfunction due to poor heart development has not been previously documented. Accepted: 22 September 1997     

新生儿遗传代谢脑病的研究进展

新生儿期发病的遗传代谢性疾病常导致脑病的发生,但由于不能及时准确的诊断及早期救治,重者死亡,即使存活也遗留严重的神经系统后遗症。尽管有相当一部分的遗传代谢脑病发病机制尚未明确,但是随着新生儿遗传代谢筛查的开展,MR1检测技术在新生儿领域不断应用,某些患儿在临床症状出现之前或出现后不久即得到及时的诊断及治疗,从而改善预后...     

连续性肾脏替代治疗在新生儿遗传代谢性疾病中的应用

目的 探讨连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)在新生儿遗传代谢性疾病合并高氨血症救治中的有效性及安全性.方法 回顾性收集并分析2016年9月至2020年3月在湖南省儿童医院新生儿科住院的遗传代谢性疾病合并高氨血症并行CRRT的新生儿的病历资料,包括一般...     

Systemic arterial pneumatosis in a neonate with necrotizing enterocolitis

Ultrasound is exquisitely sensitive for the identification of portal vein pneumatosis, which in neonates is commonly caused by necrotizing enterocolitis. We describe the ultrasound finding of systemic arterial pneumatosis in a case of necrotizing enterocolitis associated with congenital heart disease. A combination of a patent ductus venosus and an extracardiac right-to-left shunt via the great vessels through a patent ductus arteriosus provided a pathway for the pneumatosis from the portal vein to the abdominal aorta.