幼儿间断抽搐1年半伴发育落后

该文报道1例吡哆醇依赖性癫癎患儿。患儿女,2岁时因发育落后,间断抽搐1年半就诊。患儿新生儿期曾有“缺氧”病史,婴儿期早期即出现难以控制的惊厥发作,部分性发作为主,多次癫癎持续状态,多种抗癫癎药物均不能控制发作。发热感冒时抽搐发作频繁。治疗前后多次视频脑电图及头颅MRI检查均正常。曾考虑诊断为Dravet综合征,后通过ALDH7A1基因检测确诊为吡哆醇依赖性癫癎。确诊后逐渐减停抗癫癎药物,仅单纯口服吡哆醇,发作基本控制。     

小儿Sjögren-Larsson综合征临床特征及基因突变分析

目的 分析4例 Sjögren-Larsson 综合征 （Sjögren-Larsson syndrome, SLS）患儿临床特征及ALDH3A2基因突变, 以明确诊断, 并为遗传咨询和产前诊断提供依据。方法 收集 2008—2013 年中国人民解放军总医院儿童医学中心收治的 4 例 Sjögren-Larsson 综合征患儿的临床资料。抽取外周静脉血各3 mL, 应用二氧化硅法提取基因组DNA。采用聚合酶链反应（PCR）扩增ALDH3A2基因的11个外显子及其与内含子的连接区。PCR产物直接测序法检测基因突变。结果 来自3个家系的4例患儿均存在先天性鱼鳞病、智力低下、痉挛性截瘫或四肢瘫等典型临床表现。3例患儿 ALDH3A2基因测序均检出基因突变。分别为：例1, IVS5-1del G, c.1157A＞G（p.Asn386Ser）; 例2和例3, c.1157A＞G （p.Asn386Ser）纯合突变; 例4基因检测未发现编码区致病突变。结论 明确了 4 例 Sjögren-Larsson综合征患儿的基因诊断, 发现 2个ALDH3A2基因突变位点,其中 IVS5-1del G为新发突变。     

中国南方汉族人3个家族性激素耐药型肾病综合征家系CD2AP和NPHS1基因突变分析

目的 分析中国南方汉族人家族性激素耐药型肾病综合征(SRNS)家系CD2AP和NPHS1基因突变及其特点.方法 研究对象为A、B、C 3个南方汉族SRNS家系先证者及其父母,A、B 2个家系先证者的姐姐和50例尿检正常的南方汉族成年人.取所有研究对象外周静脉血,提取基因组DNA,PCR方法扩增CD2AP基因全部18个外显子和NPHS1基因全部29个外显子及其周围的部分内含子,对PCR产物直接进行DNA序列测定.结果 在3个SRNS家系先证者未检测出CD2AP基因致病突变.在B家系的先证者检测出NPHS1基因2398C＞T(R800C)杂合突变,先证者父亲亦携带此杂合突变,但先证者母亲及姐姐未发现该突变.在50例对照人群中未发现2398C＞T突变.此外,在3个先证者及50例对照人群还检测出9种已报道的CD2AP基因多态性--IVS4-25G＞A、IVS8-95G＞A、IVS10+36C＞A、IVS10-153A＞T、IVS10-110A＞G、IVS11+82T＞C、1204C＞T、IVS16+24G＞A、IVS17-66T＞C和4种已报道的NPHS1基因多态性--349G＞A、IVS24+36C＞T、3315G＞A和IVS27+45C＞T.结论 在1个中国南方汉族SRNS家系先证者检测出NPHS1基因突变--2398C＞T,证实中国南方汉族人家族性SRNS儿童存在NPHS1基因突变,提示对其需进行NPHS1基因突变分析.     

癫(癎)患儿预后与相关因素的远期随访研究

目的 分析影响癫(癎)患儿预后的相关因素,为癫(癎)的诊治和预后评估提供依据.方法 回顾性分析2003年1-12月在北京大学第一医院儿科门诊就诊的290例癫(癎)患儿的临床资料,随访患儿发作、用药、智力及精神运动发育等情况,以至少1年无发作为疗效控制指标.结果 ①经正规抗癫(癎)药物治疗,57.9%患儿发作控制满意,多数可以正常学习或生活;(②各型癫(癎)均有控制发作的可能,不同发作类型癫(癎)的控制率不同;③起病年龄越早,特别是1岁内起病者发作控制较差;④原发性癫(癎)控制率明显高于症状性或隐源性癫(癎),症状性癫(癎)预后最差;⑤大部份病例经单药治疗可以控制发作,2种药物治疗未控制者,再添加药物进行治疗,控制率无明显提高.结论 儿童癫痫的预后大多良好,有下列情况者预后差:①起病年龄小,尤其是1岁者;②同时有多种发作形式;③症状性癫(癎).     

散发性激素耐药型肾病综合征患儿30例足细胞基因突变分析

目的分析散发性激素耐药型肾病综合征(SRNS)儿童足细胞基因突变及其特点。方法研究对象为30例散发性SRNS患儿和50例尿检正常的健康志愿者。采用PCR扩增NPHS1、NPHS2和CD2AP基因全部外显子及其周围的部分内含子,WT1基因外显子8和9及其周围的部分内含子;应用DNA序列直接测定法对其PCR产物进行测序。结果在10例应用激素和免疫抑制剂治疗肾病无缓解的SRNS患儿中,发现1例携带WT1基因杂合突变——1180C>T(R394W),1例携带NPHS1基因复合杂合突变——2677A>G(T893A)和*142T>C,1例携带CD2AP基因杂合突变IVS13-137G>A。在20例应用激素或免疫抑制剂治疗肾病缓解的SRNS患儿中,发现4例患儿携带NPHS1基因单杂合突变——928G>A、IVS8+30C>T、IVS21+14G>A和IVS25-23C>T,1例患儿携带CD2AP基因单杂合突变(IVS7-135G>A)。结论对激素和免疫抑制剂均耐药的SRNS患儿需进行足细胞基因突变分析。     

小儿结节性硬化症合并癫癎的随访研究

目的：调查结节性硬化症（TSC）合并癫癎的治疗转归及癫癎反复发作的高危因素。方法：回顾性分析我院66例TSC患儿的资料。结果：66例TSC患儿中,随访47例,随访时间为7个月至9.3年,平均4.5±2.6年。患儿现在年龄7.7±4.1岁,癫癎发作类型：40%有婴儿痉挛症,51%有强直性发作,32%有部分性发作,强直-阵挛性发作占6%,多灶性发作、失张力发作、不典型失神发作、抑制性运动发作各占2%。目前使用抗癫癎药1.9±0.86种,中位数1种。26%仍然癫癎发作,70%无发作,4%死亡。手术治疗3例,均在继续用药,随访1.5年以上,无发作。应用非条件logistic回归方法分析,发现起病年龄（RR=1.8, 95% CI 1.0～3.2, P=0.050）、抗癫癎药的种类(RR=4.8, 95% CI 1.2～18.6, P=0.024)、强直发作(RR=0.003, 95% CI 0.0～0.2, P=0.04)、性别(RR=0.016, 95% CI 0.0～0.5, P=0.017）是癫癎反复发作的高危因素。30例7岁以上儿童57%例可以上普通学校, 10%上特殊学校; 33%因为智力、言语发育落后不能上学。结论：对TSC合并癫癎进行抗癫癎治疗可以达到大部分无发作。癫癎发作起病年龄早、强直发作、需要多种抗癫癎药是癫癎反复发作的高危因素。［中国当代儿科杂志,2009,11（12）：996-998］     

提高癫(癎)儿童的生活质量是治疗的最终目的

在控制癫(癎)发作的同时关注生活质量,表达了21世纪癫(癎)治疗及相关服务中的一种值得注意的趋势.癫(癎)对患者生活质量影响的因素包括癫(癎)的类型、癫(癎)灶的部位、起病年龄、发作频率、持续时间和病程,特别是抗癫(癎)药物本身对儿童生活质量的影响.在癫(癎)治疗中,对于选择药物种类要权衡利弊,既要达到较好的治疗效果,又要尽可能地减少药物对患儿智力影响程度,并提倡单药治疗.癫(癎)治疗的目的 已不再是以控制发作为终点,而以在控制发作的同时提高患者的生活质量为治疗的终点.癫(癎)的治疗应该是在控制发作及提高生活质量间找到最佳结合点.     

儿童惊吓性癫(癎)的临床及脑电图特征

目的 探讨儿童惊吓性癫(癎)的临床及脑电图特征.方法　对2003年12月-2008年3月在北京大学第一医院儿科就诊的7例惊吓性癫(癎)患儿的病因、发作诱发因素、发作类型、脑电图特点、治疗及预后进行回顾性分析.结果　7例惊吓性癫(癎)患儿中男4例,女3例;起病年龄为5个月～7.5岁.有病因学异常6例,涉及4种不同的获得性病因;有影像学异常6例,以局部脑萎缩多见.7例均有惊吓性发作,同期有自发性发作,其中4例以自发性发作起病.发作的诱因5例为声音刺激,2例为碰触刺激.惊吓性发作的类型包括强直-不典型失神发作、肌阵挛发作、肌阵挛-强直发作、强直发作及局限性发作,与自发性发作类型可相同或不同.发作期脑电图常见弥散性电压衰减图形,并可见与发作类型相关的其他图形.病例对多种抗癫NFDF4药的治疗均未见明显疗效.结论　惊吓性癫(癎)常见为症状性的反射性癫(癎),声音及碰触刺激为主要诱发因素,惊吓性发作包括全面性发作及局限性发作中的多种类型,发作期脑电图常见为弥散性电压衰减图形.本病对抗癫(癎)药治疗反应欠佳,总体预后差.     

不同抗癫癎药物治疗对癫癎患儿血脂的影响

目的 探讨癫癎患儿血脂水平的改变及应用抗癫癎药物对血脂水平的影响.方法 采用酶测定法分别测定2009年1月-2011年1月在小儿癫癎专科门诊随访治疗的55例癫癎患儿(全面性发作30例,单纯局限性发作18例,不能分类的发作7例)和30例健康体检儿童(健康对照组)血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白( HDL-C)、低密度脂蛋白(LDL-C)水平,分析癫癎患儿在单药或联合用药至少0.5a后与健康对照组比较血脂水平的变化.结果 癫癎患儿服用抗癫癎药物后引起其血脂水平的改变,与健康对照组血脂水平相比,血清TG、LDL-C显著升高(Pa＜0.01),HDL-C水平显著下降(P＜0.01);丙戊酸钠( VPA)单药治疗的癫癎患儿与健康对照组相比,TG、LDL-C升高及HDL-C降低,其差异有统计学意义(Pa＜0.05,0.01),而单用VPA与联合用药组之间及两个联合用药组间血脂水平改变的差异均无统计学意义(Pa＞0.05);联合用药组与健康对照组比较,其改变幅度VPA＞ VPA+拉莫三嗪＞VPA+左乙拉西坦,但差异均无统计学意义(Pa＞0.05).结论 癫癎患儿服用抗癫癎药物后存在血脂水平的改变,以单用VPA的改变最大.     

中国南方汉族散发性先天性肾病综合征NPHS1基因突变1例

目的 分析中国南方汉族1例散发性先天性肾病综合征(CNS)患儿NPHS1基因突变及其特点.方法 研究对象为1例中国南方汉族CNS患儿及其父母,对照人群为50例尿液检查正常的南方汉族成年人.取所有研究对象外周静脉血3 mL,提取基因组DNA,PCR扩增NPHS1全部29个外显子及其周围的部分内含子和启动子全长序列,对PCR产物直接进行DNA序列测定.结果 在CNS患儿检测出NPHS1基因3250insG(V1084fsX1095)纯合突变,其父母分别携带3250insG杂合突变.在CNS患儿及其父母还检测出3种已报道的NPHS1基因多态性--349G＞A、3315G＞A和IVS27+45C＞T.在50例对照人群中未发现NPHS1基因3250insG变异;但检测出349G＞A、3315G＞A和IVS27+45C＞T基因多态性.结论 首次在1例中国南方汉族CNS患儿发现了NPHS1基因纯合突变--3250insG(V1084fsX1095),表明中国南方汉族散发性CNS患儿存在NPHS1基因突变,提示对中国南方汉族散发性CNS患儿需进行NPHS1基因突变分析.     

Pyridoxine dependent epilepsy: Is late onset a predictor for favorable outcome?

Aim

In pyridoxine dependent epilepsy (PDE), patients usually present with neonatal seizures. A small subgroup is characterized by late-onset beyond 2 months of age. We aim to analyze the observation of relatively good cognitive outcome in this subgroup of late-onset PDE patients.

EFFECTS OF AN ANTENATAL LOAD OF PYRIDOXINE (VITAMIN B6) ON THE BLOOD OXYGEN AFFINITY AND PROLACTIN LEVELS IN NEWBORN INFANTS AND THEIR MOTHERS

ABSTRACT. The effects of a loading dose of pyridoxine (100 mg) given intramuscularly or per os to 24 earlier non-supplemented pregnant women at term was investigated. The in vitro oxygen affinity (P₅₀) and the prolactin level in both maternal and newborn blood was sampled. The blood P₅₀ values were measured by a variant of "mixing method". Blood prolactin levels were determined by RIA. After pyridoxine administration, the maternal P₅₀ values increased moderately and the newborns' cord blood P₅₀ values increased significantly when compared with the control group's (number of cases 12) values. The decrease of blood oxygen affinity was most pronounced in the supplemented groups in newborns' capillary blood at the age of five days. The pyridoxine supplementation had no effect on the maternal and the newborns' cord blood prolactin level or on the daily amount of breast milk. Pyridoxine supplementation of the mother at labour may influence favourably the oxygen transport function of the newborn's blood and it may be especially advantageous in early postnatal adaptation disturbances of newborns.     

Pyridoxal‐5‐phosphate plasma concentrations in children receiving tuberculosis chemotherapy including isoniazid

Aim: Little is known about pyridoxine nutriture of children treated with isoniazid (INH) regimens. This study documents plasma pyridoxal 5′‐phosphate (PLP) concentrations in children, HIV‐infected and HIV‐uninfected, receiving INH regimens. Methods: Children from the Western Cape of South Africa hospitalized for tuberculosis (TB) management were studied. Plasma PLP concentrations were determined on enrolment, 1‐month after commencing TB treatment, and again after 4‐month’s treatment. The children received a supplement meeting pyridoxine requirements. Results: Nineteen HIV‐infected and 33 HIV‐uninfected children received INH (dosage range 4–20 mg/kg) daily. Mean PLP plasma concentrations on enrolment were 8.32 (SD 6.75) ng/mL and 11.28 (SD 3.02) ng/mL in HIV‐infected and HIV‐uninfected children, respectively (p = 0.11) and after 4‐month’s treatment 6.75 (SD 2.71) ng/mL and 14.76 (SD 7.96) ng/mL (p < 0.001). On enrolment 9 (50%) HIV‐infected and 5 (15%) HIV‐uninfected children (p = 0.016) had suboptimal PLP concentrations (<6 ng/mL); after 4‐month’s treatment 8 (42%) and 2 (6%) (p = 0.004). Conclusion: Plasma PLP concentrations in children treated for TB were low on enrolment in HIV‐infected and HIV‐uninfected children; after 4‐month’s treatment low values were still common in HIV‐infected children. Additional pyridoxine supplementation of malnourished children treated for tuberculosis is advisable, particularly those HIV‐infected.     

Prevalence of pyridoxine dependent seizures in south Indian children with early onset intractable epilepsy: A hospital based prospective study

OBJECTIVES: Determine the prevalence of pyridoxine dependent seizures in children less than 16 years of age attending a teaching hospital in south India with early onset (before 3 years) intractable epilepsy of unknown aetiology, using the criteria proposed by Baxter. METHOD: A cohort of 81 children, fulfilling the above criteria, was given 15 mg/kg/day of oral pyridoxine for 7 days. Non-responders were given a further 7-day trial of 30 mg/kg/day. Diagnosis of pyridoxine dependent seizures was made according to the criteria proposed by Baxter. RESULT: Six children (7.4%; four boys and two girls) were identified as definite cases and were continued on B6, without recurrence of seizures. Median age of seizure onset and diagnosis were 2.5 months and 2 year 9 months, respectively. No significant complications were observed with B6 therapy. CONCLUSION: Chance of identifying PDS is not low in a subpopulation of children with intractable early onset cryptogenic epilepsy using the criteria proposed by Baxter, which warrants a therapeutic trial with B6 in them.     

Homocystinuria (cystathionine synthase deficiency). Results of treatment in late-diagnosed patients

The clinical outcome in 12 late-diagnosed patients with homocystinuria is reported. Three children died: all were mentally damaged and were never treated effectively. Eight children have been treated with pyridoxine—or with a low-methionine diet with supplemental l-cystine—for 2 to 9 years. Follow-up of these patients shows a striking improvement in behaviour and intellectual development in close correlation to the biochemical normalisation. No thromboembolic episodes occurred in adequately treated patients. However, in one child thrombosis of the retinal artery developed during dietary failure. In another patient the characteristic symptoms of an endangiitis obliterans completely disappeared. Both the reversibility and the improvement of some of the main sequelae in homocystinuria emphasize the need to treat all patients, regardless of their age at diagnosis.     

Early diagnosis of pyridoxine-dependent epilepsy: Video-EEG monitoring and biochemical and genetic investigation

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive metabolic disease. A delay of treatment may affect outcome and early initiation of pyridoxine based on effective diagnosis is crucial to ensure good cognitive outcome in neonates. A consensus for the diagnosis of PDE is based on refractive seizures and responsiveness to pyridoxine, however, a growing body of evidence suggests that additional elements should be considered which include biochemical data, genetic screening, and EEG monitoring. We present a case study of a neonate with PDE, who presented with misleading clinical presentation and a novel mutation in the antiquitin (ALDH7A1) gene (A294V), and highlight important aspects in order to consider the definition of diagnosis and management of PDE in the light of more recent data.     

Novel therapy for pyridoxine dependent epilepsy due to ALDH7A1 genetic defect: l-arginine supplementation alternative to lysine-restricted diet

Background and hypothesisPyridoxine dependent epilepsy (PDE) due to mutations in the ALDH7A1 gene (PDE-ALDH7A1) is caused by α-aminoadipic-semialdehyde-dehydrogenase enzyme deficiency in the lysine pathway resulting in the accumulation of α-aminoadipic acid semialdehyde (α-AASA). Classical presentation is neonatal intractable seizures with a dramatic response to pyridoxine. Pyridoxine therapy does not prevent developmental delays in the majority of the patients. We hypothesized that l-arginine supplementation will decrease accumulation of α-AASA by competitive inhibition of lysine transport into the central nervous system and improve neurodevelopmental and neurocognitive functions in PDE-ALDH7A1.MethodsA 12-year-old male with PDE-ALDH7A1 was treated with l-arginine supplementation as an innovative therapy. Treatment outcome was monitored by cerebral-spinal-fluid (CSF) α-AASA measurements at baseline, 6th and 12th months of therapy. Neuropsychological assessments were performed at baseline and 12th months of therapy.Resultsl-arginine therapy was well tolerated without side effects. CSF α-AASA was decreased 57% at 12th months of therapy. Neuropsychological assessments revealed improvements in general abilities index from 108 to 116 and improvements in verbal and motor functioning at 12th months of therapy.ConclusionThe short-term treatment outcome of this novel l-arginine supplementation therapy for PDE-ALDH7A1 was successful for biochemical and neurocognitive improvements.     

Hypophosphatasia as a rare cause of neonatal seizures

Severe forms of hypophosphatasia due to loss-of-function in the ALPL gene may present with diverse neurological problems including pyridoxine-responsive seizures. We present a short report of pyridoxine-responsive neonatal seizures. Due to severe osteopenia with unmeasurable levels of alkaline phosphatase, targeted genetic screening was performed and two pathogenic variants in the gene for the nonspecific alkaline phosphatase confirmed the diagnosis of hypophosphatasia. We would like to emphasize the importance of considering infantile hypophosphatasia in the differential diagnosis of pyridoxine-responsive seizures with concomitant low alkaline phosphatase level and bone pathology, especially with the new treatments becoming available in the future.