肝脏增大、反复发作性肌无力和低血糖

患儿,男,11岁,间断乏力、行走困难6年,发作性意识不清4年;辅助检查提示严重代谢性酸中毒、低血糖、肝功能异常,CT示肝脏明显增大、呈脂肪密度影。给予补液、纠酸、纠正低血糖,以及左卡尼汀、复合维生素B、辅酶Q10等治疗,患儿持续昏迷、代谢性酸中毒及低血糖难以纠正,患儿死亡。血、尿有机酸筛查和基因检测证实为电子转运黄素蛋白脱氢酶编码基因(ETFDH)缺陷所致的迟发型戊二酸尿症Ⅱ型(GAⅡc型)。GAⅡc型是一种发病率很低的遗传性代谢病,易误诊误治。对于反复乏力或活动耐力下降、低血糖、肝脏明显增大伴肝功能异常的患儿,应考虑GAⅡ型的可能,尿有机酸分析和血串联质谱分析可提供诊断线索,ETFDH基因分析可提供确诊依据。     

儿童食物蛋白诱导的小肠结肠炎综合征

食物蛋白诱导的小肠结肠炎综合征(FPIES)是一种非IgE介导的胃肠道过敏性疾病,目前发病机制尚不明确,通常于婴儿时期发病,临床表现缺乏特异性,常急性起病,表现为反复发作的喷射性呕吐,伴或不伴有腹泻,严重病例可出现代谢紊乱、嗜睡、低血压、低体温、肌张力低下甚至休克.诊断主要依赖于病史、典型的临床表现以及回避可疑致敏食物...     

糖原累积病Ⅰ型研究进展

糖原累积病I型是糖原累积病中较常见且较严重的一种类型.根据典型临床表现和基因检测,该疾病可以得到明确诊断.饮食治疗可改善代谢紊乱和长期预后,但无法逆转部分并发症.该文对糖原累积病I型的分子病理学、代谢紊乱机制、诊断、治疗及长期预后等研究进展加以综述.     

以癫(癎)发作为主要表现的甲状腺功能亢进症

目的 探讨甲状腺功能亢进症(甲亢)伴癫(癎)样发作的临床特点及发病机制.方法 总结本院2例住院甲亢患儿,均为女童.1例3岁7个月患儿出现高代谢症状9个月余,未给予正规治疗出现抽搐发作;另1例12岁患儿已诊断甲亢并口服抗甲亢药物,症状好转后自行停药,1周后出现抽搐发作.2例患儿的发作形式均为全面性强直-阵挛发作.根据患儿临床表现、实验室检查、治疗及转归,同时回顾性分析PUBMED检索及中文医学期刊全文数据库,从1975年至今国内外相关文献报道共18例甲亢伴癫(癎)样发作患儿(年龄3～18岁;男7例,女11例).结果 甲亢伴发癫(癎)样发作形式主要为全面性强直一阵挛发作,共18例;2例青春期患者表现为肌阵挛发作.其中有3种临床表现形式:8例(8/20例,占40%)以癫(癎)样发作为首发症状,分别在首发症状出现1个月～2 a才确诊为甲亢;癫(癎)样发作为继发症状9例(9/20例,占45%),在确诊为甲亢2个月～4 a出现癫(癎)样发作,多为甲亢控制欠佳或中断药物时发生;癫(癎)患者并甲亢时癫(癎)样发作加重3例(3/20例,占15%),均在青春期合并甲亢时发作次数明显增加.结论 甲亢可引起癫(癎)样发作,其发作与甲状腺激素水平升高关系密切;甲亢与癫(癎)可能存在某些共同的免疫发病机制.     

酪氨酸血症Ⅰ型的诊治进展

酪氨酸血症Ⅰ型是一种常染色体隐性遗传病,主要累及肝脏和肾脏,严重者可危及生命,患者并发肝细胞癌风险大.诊断需依据临床表现,血酪氨酸及琥珀酰丙酮水平升高,或尿琥珀酰丙酮升高.尼替西农是治疗该病的主要药物,同时需给予低酪氨酸及苯丙氨酸的饮食治疗.部分患者进行了肝移植,并取得较好的效果.基因治疗已开始在动物模型中进行研究.     

特发性肺含铁血黄素沉着症50例

目的探讨特发性肺含铁血黄素沉着症(IPH)的临床表现、实验室特点及治疗。方法对1996年1月-2006年1月收治50例儿童IPH的临床表现、实验检查(包括血常规、铁代谢及骨髓检查,痰、胃液或支气管灌洗液寻找含铁血黄素细胞,胸部影像学)资料进行分析。结果IPH好发于6~14岁学龄儿童。咳嗽、贫血和咯血为最常见症状。胸片表现多样化。诊断以临床表现为主要线索,胸片、CT有重要辅助价值,结合反复胃液或痰中找到含铁血黄素细胞,必要时行支气管灌洗液检查,并除外继发性IPH,即可确诊。用肾上腺皮质激素治疗可改善症状。结论儿童IPH临床表现缺乏特异性。胸片、CT和反复胃液或痰含铁血黄素细胞检查有助于本病诊断。激素治疗可缓解症状,改善预后。     

儿童板层型灰质异位症伴癫(痫)发作三例并文献复习

目的 观察并探讨板层型灰质异位症伴癫(痫)发作儿童的临床表现、脑电图及影像学特点.方法 收集板层型灰质异位症的癫(痫)患儿病例资料3例,对其临床表现、影像学及脑电图特点进行回顾性分析,并电话随访其治疗及预后情况.结果 本研究中板层型灰质异位症患儿均为女性,均伴有反复癫(痫)发作,并伴有一定程度发育落后或学习困难;影像学均呈典型的“双皮质征”改变;其癫(痫)发作形式复杂,以全面发作或复杂部分性发作为主,可混合不典型失神发作或失张力发作,发作前有恐惧、腹痛等先兆,脑电图呈多灶性改变,以枕、顶、颞叶最显著;3例患儿均为联合用药治疗,脑电图改变及临床发作均有好转趋势.结论 对儿童期反复癫(痫)发作伴有一定智力缺陷的女性患儿需注意是否为板层型灰质异位症,磁共振发现“双皮质征”改变为确诊依据,其癫(痫)发作早期治疗可有较好的效果,抗癫(痫)治疗建议联合用药.     

以癫痫发作为主要表现的甲状腺功能亢进症

目的探讨甲状腺功能亢进症（甲亢）伴癫癎样发作的临床特点及发病机制。方法总结本院2例住院甲亢患儿,均为女童。1例3岁7个月患儿出现高代谢症状9个月余,未给予正规治疗出现抽搐发作;另1例12岁患儿已诊断甲亢并口服抗甲亢药物,症状好转后自行停药,1周后出现抽搐发作。2例患儿的发作形式均为全面性强直-阵挛发作。根据患儿临床表现、实验室检查、治疗及转归,同时回顾性分析PUBMED检索及中文医学期刊全文数据库,从1975年至今国内外相关文献报道共18例甲亢伴癫癎样发作患儿（年龄3-18岁;男7例,女11例）。结果甲亢伴发癫癎样发作形式主要为全面性强直-阵挛发作,共18例;2例青春期患者表现为肌阵挛发作。其中有3种临床表现形式：8例（8/20例,占40%）以癫痫样发作为首发症状,分别在首发症状出现1个月-2a才确诊为甲亢;癫痫样发作为继发症状9例（9/20例,占45%）,在确诊为甲亢2个月-4a出现癫痫样发作,多为甲亢控制欠佳或中断药物时发生;癫痫患者并甲亢时癫痫样发作加重3例（3/20例,占15%）,均在青春期合并甲亢时发作次数明显增加。结论甲亢可引起癫痫样发作,其发作与甲状腺激素水平升高关系密切;甲亢与癫痫可能存在某些共同的免疫发病机制。     

特发性肺含铁血黄素沉着症21例

特发性肺含铁血黄素沉着症 (ＩＰＨ)是小儿时期一种少见疾病 ,常误诊或漏诊。本文总结我院收治的 2 1例ＩＰＨ ,并对其误诊原因、诊断及治疗进行探讨。临床资料一、一般资料　本组 2 1例 ,男 12例 ,女 9例 ,年龄 1～ 5ａ14例 ,～ 8ａ 5例 ,～ 12ａ 2例。病程 2个月～ 5ａ ,发病年龄 10个月～ 9ａ。仅 2例病前食用过牛奶 ,均无过敏性疾病史。二、临床表现　 2 1例均有反复发作咳嗽、气急、面色苍白 ;12例伴发热 ;9例以咳嗽、咯血为首发症状 ,年龄 >5ａ。肝脾肿大 12例 ,心脏杂音 11例 ,黄疸、肺部罗音各 3例。重症者可突然出现呼吸急促、面色…     

原发性肉碱缺乏症与心肌病

左旋肉碱（又称左卡尼汀,简称肉碱）是协助长链脂肪酸从细胞质转运至线粒体进行β氧化的重要物质。肉碱缺乏导致长链脂肪酸代谢障碍,尤其是在饥饿和应激情况下导致能量产生不足。原发性肉碱缺乏症属常染色体隐性遗传病,SLC22A5基因突变导致肉碱转运蛋白OCTN2缺陷,引起线粒体脂肪酸β氧化障碍,是少数可治疗的代谢性肌肉病之一。原发性肉碱缺乏症患者可在任何年龄阶段起病,轻重不一,个体差异显著。婴儿期可在上呼吸道感染、胃肠炎等普通疾病诱发下出现急性代谢紊乱,常见低酮症性低血糖、代谢性酸中毒、高尿酸血症,一些患儿伴心律紊乱、心功能衰竭、脂肪肝、脑损害。在儿童至成人可表现为慢性进行性或急性心肌病及骨骼肌肌肉病,早期诊断、左卡尼汀支持治疗是挽救生命的关键。     

多种酰基辅酶A脱氢酶缺乏症儿童与成人患者临床特点比较

目的比较儿童和成人多种酰基辅酶A脱氢酶缺乏症(MADD)患者的临床和实验室检查特点。方法对12例儿童和19例成人MADD患者进行常规实验室检查、血酰基肉碱谱及尿有机酸分析。对中国人电子转运黄素蛋白脱氢酶(ETFDH)基因常见突变A84T通过DNA测序方法进行筛检。结果儿童MADD患者临床表现高度异质,可表现为肌无力、肝大、低酮性低血糖、肥厚性心肌病或脑发育不良及脱髓鞘病变;而成人患者均以肌无力起病。成人和儿童MADD有肝酶和CK升高,血多种酰基肉碱升高,多数伴有二羧酸尿。儿童组3例死亡,成人组全部存活。存活患者的症状和生化指标治疗后好转或正常。A84T突变在儿童和成人患者的发生率分别为20.8%(5/24)和21%(8/38)。结论儿童与成人MADD患者的临床表现和预后存在差异,成人患者预后好;A84T突变可能与轻型相关。[临床儿科杂志,2012,30(5):446-449]     

Cyclic vomiting syndrome masking a fatal metabolic disease

Disorders of fatty acid oxidation are rare but can be fatal. Hypoglycaemia with acidosis is a cardinal feature. Cases may present during early childhood or can be delayed into adolescence or beyond. We present a case of multiple acyl-coenzyme A dehydrogenase deficiency (MADD), an extremely rare disorder of fatty acid oxidation. Our 20-year-old patient presented with cardiovascular collapse, raised anion gap metabolic acidosis and non-ketotic hypoglycaemia. She subsequently developed multi-organ failure and sadly died. She had a previous diagnosis of cyclic vomiting syndrome (CVS) for more than 10 years, warranting frequent hospital admissions. The association between CVS and MADD has been made before though the exact relationship is unclear. All patients with persistent severe CVS should have metabolic investigations to exclude disorders of fatty acid oxidation. In case of non-ketotic hypoglycaemia with acidosis, the patient should be urgently referred to a specialist in metabolic diseases. All practitioners should be aware of these rare disorders as a cause of unexplained acidosis.     

Treatment of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria). Experience with diet, riboflavin, and GABA analogue.

The autosomal recessive inherited disorder glutaryl-CoA dehydrogenase deficiency (glutaric aciduria) runs a progressive course with severe choreoathetosis and dystonia, eventually leading to total helplessness and early death. Theree patients were observed during therapeutic trials with a protein-low diet, riboflavin and GABA analogue. Diet and riboflavin had a slight-to-moderate effect on the clinical symptoms; the excretion of glutaric acid and 2-amino-adipic acid decreased considerably during treatment. Regression of neurologic symptoms was observed during treatment with GABA analogue. It is concluded that the patients should be treated as early as possible with protein-low diet, riboflavin, and GABA analogue.     

Cardiomyopathy in Multiple Acyl-CoA Dehydrogenase Deficiency

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive defect of the electron transfer flavoprotein or ubiquinone oxidoreductase, resulting in abnormal fatty acid, amino acid, and choline metabolism, leading to metabolic acidosis, hypoglycemia, “sweaty-feet” odor, and early neonatal deaths. This report presents a child diagnosed with this disease at birth by newborn screening using the mass spectrometer, who died suddenly at the age of 6 months. The echocardiogram revealed pericardial effusion, thickened ventricular musculature, and insufficiency of both the atrio-ventricular valves. The autopsy showed immense cardiomegaly, fatty infiltration, and hypertrophy of the ventricles. This is the first detailed case report of clinico-pathological correlation of MADD in an infant and brings into light a rare form of cardiomyopathy as a differential diagnosis in critically ill patients.     

Riboflavin (vitamin B2) treatment of neonatal pathological jaundice

The effect of traditional blue-light and riboflavin combined with blue-light was compared in newborns affected by ABO incompatibility, admitted for exchange transfusion. During the period of preparation for the intervention 14 patients were treated with blue light alone and 14 patients with riboflavin combined with phototherapy. A single dose of 10 mg/kg riboflavin was administered intravenously. The duration of treatment was three hours in both groups. The effect of phototherapy was markedly enhanced by the additional riboflavin, by the end of the 3-hour period a significant fall of serum bilirubin was demonstrated in the 14 patients treated with blue light and riboflavin while in the patients treated with phototherapy alone the bilirubin level continued to rise. There was no difference in the activity of the antioxidant enzymes superoxide dismutase and catalase, and in lipid peroxidation between the groups.     

Vitamin concentrations in very low birth weight infants given vitamins intravenously in a lipid emulsion: measurement of vitamins A, D, and E and riboflavin

Because total parenteral nutrition with vitamins added to the glucose-amino acid mixture is often associated with a reduction in blood levels of vitamin A (retinol) during the routine treatment of many very low birth weight (VLBW) infants (less than 1500 gm), and because retinol losses in the plastic delivery system can be prevented by adding the vitamins to an intravenous lipid emulsion, seven VLBW infants with a mean birth weight of 900 gm (range 450 to 1360 gm) were given 40% of a unit dose vial, per kilogram of body weight, of a multivitamin preparation (M.V.I. Pediatric) (280 micrograms retinol; 160 IU vitamin D; 2.8 mg tocopherol; 0.68 mg riboflavin) in a lipid emulsion, Intralipid. After treatment with the intralipid-vitamin mixture for 19 to 28 days, plasma vitamin A (retinol) concentrations increased significantly from 11.0 +/- 0.76 (mean +/- SEM) before intralipid to 19.2 +/- 0.97 micrograms/dl after the intralipid-vitamin mixture (p less than 0.01); 25-hydroxyvitamin D concentrations increased from an initial value of 12.6 +/- 2.6 to 20.2 +/- 1.9 mg/dl (p less than 0.01); alpha-tocopherol concentrations increased from an initial value of 0.31 +/- 0.06 to 2.44 +/- 0.13 mg/dl (p less than 0.01); and riboflavin levels increased from 64.1 +/- 7.8 ng/ml to concentrations between 20 and 100 times the initial level. Erythrocyte riboflavin levels increased from 71.8 +/- 14 initially to 166 +/- 41 ng/gm hemoglobin, and erythrocyte flavin-adenine dinucleotide levels increased similarly from 972 +/- 112 initially to 2005 +/- 294 ng/gm hemoglobin. These results show that the addition of M.V.I. Pediatric to Intralipid decreases the extensive in vivo loss of retinol and is associated with an increase in plasma retinol concentrations in VLBW infants. The daily doses of vitamins D (160 IU/kg) and E (2.8 mg/kg) appear sufficient, but the dose of vitamin A (280 micrograms/kg) is insufficient to raise blood levels of all infants into the normal range. The current dose of riboflavin is excessive and may be harmful.     

Significance of phototherapy-induced riboflavin deficiency in the full-term neonate.

As a result of impaired fatty acid oxidation, a characteristic urinary dicarboxylic aciduria occurs in the riboflavin deficient animal. We compared the occurrence of riboflavin deficiency induced by phototherapy with changes in urinary organic acid profiles in 8 full-term, breast-fed neonates who received phototherapy for hyperbilirubinemia, and in 10 full-term, breastfed controls. Riboflavin status was assessed by measuring flavin adenine dinucleotide saturation of erythrocyte glutathione reductase. All 8 neonates exposed to phototherapy developed riboflavin deficiency (p less than 0.001). Riboflavin deficiency was progressive with the duration of phototherapy. None of the controls was riboflavin deficient. Urine organic acid profiles indicative of mitochondrial acyl-CoA dehydrogenase activity (fatty acid beta-oxidation, quantitated by gas chromatography mass spectrometry) showed no changes between the study and control groups in mono-, di-, or tricarboxylic acids or other organic acids. The riboflavin deficiency induced by phototherapy in full-term neonates was not of sufficient severity to limit riboflavin-dependent fatty acid oxidation.     

Multiple acyl-CoA-dehydrogenase deficiency (MADD): use of acylcarnitines and fatty acids to monitor the response to dietary treatment.

The treatment of multiple acyl-CoA-dehydrogenase deficiency (MADD) includes a low-fat, low-protein, high-carbohydrate diet, avoiding long fasting periods. However, there is no useful biochemical marker to determine the response to different diets or fasting periods. The aims of this study are to report a patient with MADD, diagnosed through a newborn screening program using tandem mass spectrometry, to assess her response to different feedings, and to evaluate the usefulness of acylcarnitines and FFA to monitor the response to dietary changes. The patient was diagnosed at 6 d. Family history revealed three dead siblings. Five tests were performed, one with breast milk and the subsequent four after giving the patient a bottle of a low-fat, low-protein formula (F), F with glucose polymers (GP), F+GP plus uncooked corn starch (CS), or F+GP+CS preceded by amylase. The results showed that acylcarnitines, FFA, and total nonesterified fatty acids levels were greatly improved at 2 and 4 h on F+GP compared with breast milk. At 6 mo of age, the test with F+CS was repeated to assess the response to a longer fast. The results were similar at 2 and 4 h, but showed a marked increase of acylcarnitines, FFA, and total nonesterified fatty acids at 6 h. The increase of these metabolites could not be avoided by the use of F+GP+CS, but was prevented when amylase was used simultaneously. The patient is currently 3.9 y old and has normal growth and development. We conclude that diagnosis of MADD through a newborn screening program using tandem mass spectrometry is suitable; acylcarnitines and FFA are useful to monitor the response to treatment; and exogenous amylase allows the use of CS in small children with MADD. This therapeutic approach may be an alternative to the use of continuous overnight feedings used for young children with severe fatty acid oxidation defects. Early diagnosis and treatment may change the natural history of MADD.     

维生素B2治疗有效的晚发型戊二酸尿症Ⅱ型

目的 探讨戊二酸尿症Ⅱ型(glutaric aciduria typeⅡ,GAⅡ)的诊断和治疗。方法 应用气相色谱-质谱分析技术(GC-MS)对2例肌无力患儿的尿滤纸片标本进行有机酸分析。确诊为GAⅡ型后,在低蛋白、低脂肪、高碳水化合物饮食控制的基础上,应用VitB2进行治疗,并观察治疗前后临床、生化及尿有机酸分析等方面的变化。结果 (1)两患儿尿滤纸片标本有机酸分析检出大量戊二酸、异戊酰甘氨酸、乙基丙二酸及己二酸、辛二酸、癸二酸等二羧酸,提示为戊二酸尿症Ⅱ型;(2)经饮食控制和VitB2治疗后,2例患儿的肌无力症状明显好转,肌力明显增强,四肢肌张力恢复正常,尿有机酸分析显示上述有机酸的排出量逐步降低、甚至消失,血清谷-草转氨酶、肌酸激酶以及乳酸脱氢酶水平均较治疗前显著降低。血氨基本降至正常水平。结论 戊二酸尿症是一种严重的先天代谢障碍性疾病。部分本症患儿在低蛋白、低脂肪、高碳水化合物饮食控制的基础上,应用VitB2进行治疗,可取得较好的临床效果。     

Limiting light-induced lipid peroxidation and vitamin loss in infant parenteral nutrition by adding multivitamin preparations to Intralipid

Parenteral lipids are susceptible to light-induced peroxidation, particularly under phototherapy. Ascorbic acid is protective. The aim of this study was to investigate whether dark delivery tubing and/or coadministration of multivitamin preparations could prevent peroxidation of Intralipid without undue vitamin loss. In experiments carried out on the benchtop, lipid peroxidation occurred in ambient light and was more extensive under phototherapy. Dark tubing decreased peroxide formation, but only by about 65%. In simulated clinical conditions in which solutions were pumped through standard clear or dark minibore plastic tubing, Intralipid accumulated lipid peroxides as measured by the FOX assay (280 µM) or as triglyceride hydroperoxides (52 µM). Multivitamin preparations (MVIP or completely, and were fully protective when used with dark tubing. There was loss of riboflavin (65% from Soluvit and 35% from MVIP) in clear tubing but this was decreased to 18% and 11%, respectively, in dark tubing. Ascorbate loss was 20% (MVIP) and 50% (Soluvit) and only slightly less in dark tubing. Ascorbate loss was also seen in the absence of Intralipid and is due to riboflavin-induced photo-oxidation.Conclusion: Multivitamin preparations protect Intralipid against light-induced formation of lipid hydroperoxides, and administering multivitamins with Intralipid via dark delivery tubing provides a practical way of preventing peroxidation of the lipid while limiting vitamin loss. This procedure should be considered for routine use as well as with phototherapy. Soluvit/Vitlipid) inhibited peroxide formation almost