Novel features in the evolution of adenylosuccinate lyase deficiency

BackgroundAdenylosuccinate lyase (ADSL) deficiency is an autosomal recessive disorder of the purine synthesis which results in accumulation of succinylpurines (succinyladenosine (S-Ado) and succinylamino-imidazole carboxamide riboside (SAICAr)) in body fluids. Patients present developmental delay, often accompanied by epilepsy and autistic spectrum disorders.ObjectivesTo describe atypical neurological features in the evolution of three novel unrelated cases of ADSL deficiency.PatientsA 9-year-old boy with severe cognitive impairment and autistic behaviour received d-ribose therapy for one year. Drug withdrawal was associated with acute neurological deterioration, severe brain atrophy and demyelination on MRI. The second patient is a 5.5-year-old girl with mild developmental delay who presented a benign course with moderate cognitive impairment as the only feature in her evolution. The final patient is a 14-year-old boy with severe cognitive impairment who developed drug-resistant epilepsy and bathing reflex seizures, progressive spasticity in the lower limbs and thoracic deformity.MethodsSAICAr and S-Ado in urine were analysed by HPLC with diode array detection. Diagnosis was confirmed by molecular analysis of the ADSL gene.ResultsAn elevation of S-Ado and SAICAr excretion in urine was detected in all three patients. The patients were homozygous for the missence change p.I369L and for the novel change p.M389V.ConclusionDrug-resistant epilepsy and specific therapeutic interventions may modify the neurological outcome in ADSL deficiency. d-ribose must be considered with caution as, in our experience, it returns no clinical benefit and drug withdrawal can precipitate status epilepticus and acute neurological deterioration.     

Paediatric Castleman disease: report of seven cases and review of the literature

Castleman disease is a distinct lymphoproliferative disorder of unknown origin. Seven new cases in children are reported here and 76 cases from the paediatric literature are reviewed. The disease has been reported in 46 females and 37 males, their age ranging from 2 months to 17 years. The disease was localized in 72 cases and multicentric in 11 cases. The hyalinovascular type was more frequently encountered (54%) than the plasma cell type (24%). Laboratory abnormalities were more often associated with the plasma cell type and were mainly represented by anaemia and hypergammaglobulinaemia. Treatment of the localized tumour consisted of surgical excision, whereas treatment of the multicentric form was medical, comprising prednisone and other immunosuppressor drugs. The disease in the paediatric population seems to have a more favourable course than in adults. Conclusion The paediatric features of the disease suggest that Castleman disease in this population could represent an earlier form of the pathology or even suggest a benign lymphoproliferative disorder. Received: 14 November 1997 / Accepted in revised form: 9 September 1998     

Malignant mesothelioma in children: report of seven cases and review of the literature

Seven children with malignant mesothelioma have been seen at Memorial Hospital since 1953. In six, the origin was at the pleura and in one at the peritoneum. None of the patients related a history of exposure to asbestos. Two patients lived more than five years. The other five patients died within two years of the diagnosis. Distant metastases were seen in four of the patients, including three who had metastases to brain. Surgery or radiotherapy were not effective in controlling the disease in most of the patients. One patient had a complete response to a combination of Adriamycin, cyclophosphamide, and vincristine and has remained free of disease for 5 1/2 years. The seven cases are reviewed, as are the other 42 cases of malignant mesothelioma in children reported in the literature.     

Magnetic resonance imaging patterns of treatment-related toxicity in the pediatric brain: an update and review of the literature

Treatment-related neurotoxicity is a potentially life-threatening clinical condition that can represent a diagnostic challenge. Differentiating diagnoses between therapy-associated brain injury and recurrent disease can be difficult, and the immediate recognition of neurotoxicity is crucial to providing correct therapeutic management, ensuring damage reversibility. For these purposes, the knowledge of clinical timing and specific treatment protocols is extremely important for interpreting MRI patterns. Neuroradiologic findings are heterogeneous and sometimes overlapping, representing the compounding effect of the different treatments. Moreover, MRI patterns can be acute, subacute or delayed and involve different brain regions, depending on (1) the mechanism of action of the specific medication and (2) which brain regions are selectively vulnerable to specific toxic effects. This review illustrates the most common radiologic appearance of radiotherapy, chemotherapy and medication-associated brain injury in children, with special focus on the application of advanced MRI techniques (diffusion, perfusion and proton spectroscopy) in the diagnosis of the underlying processes leading to brain toxicity.     

Magnetic resonance imaging diagnosis of a cerebral aneurysm in an infant. Case report and review of the literature

A posterior cerebral artery aneurysm presented as a seizure disorder in a 7-week-old infant. A small hemorrhage in the posterior thalamus was seen on CT scan. However, magnetic resonance imaging (MRI study) demonstrated an aneurysm and appropriate therapy was carried out. The incidence, natural history, etiology, and surgical treatment of these lesions are reviewed, and the usefulness of MRI in their diagnosis is emphasized.     

新生儿凝血因子Ⅶ缺乏症2例报告并文献复习

目的 探讨新生儿期发病的遗传性凝血因子Ⅶ缺乏症（FⅦD）的临床特征、诊断和治疗。 方法 对广州市妇女儿童医疗中心确诊的2例新生儿FⅦD的临床表现、诊治过程和基因检测情况进行回顾性分析，并通过复习相关文献，分析和总结有关国内外新生儿FⅦD的文献报道。结果 2例FⅦD患儿均为女性，临床表现为严重消化道和颅内出血，实验室特点为反复、非VitK1依赖的凝血酶原时间（PT)持续延长，部分凝血酶原时间（APTT）正常，凝血因子Ⅶ活性分别为1.5%和3%，分别于31 d和6个月再次发生大面积颅内出血而死亡，基因检测证实均为F基因IVS7+1G＞T剪切位点纯合突变。文献复习共检索到22例新生儿期FⅦD，合并本文2例后共24例。24例均为足月，男女均可发病，多为生后7 d内发病（17/24，70.8%）；首发症状依次为消化道出血9例、神经系统症状（嗜睡、抽搐和反应差等）8例、皮肤苍白7例。颅内出血比例高（23/24）；PT显著延长，Ⅶ因子活性明显下降（≤5%占83.3%）；病死率及致残率高（70.8%）；14例经基因检测确诊。结论 FⅦD在新生儿期发病罕见，一旦发病，易发生致命性出血，预后不良。PT延长且不易纠正，Ⅶ因子活性显著下降即可临床诊断，F基因某些位点突变可导致严重出血，基因诊断有助于产前诊断。     

线粒体乙酰乙酰辅酶A硫解酶缺乏症一家系报告并文献复习

目的探讨线粒体乙酰乙酰辅酶A硫解酶缺乏症(简称T2缺乏症)的诊断及预后。方法回顾性分析一家系中3例T2缺乏症患儿的临床资料,并复习相关文献。结果例1和例2为先证者,男孩,同卵双胞胎,因发热、呕吐、气促入院,血气分析均显示严重的代谢性酸中毒,尿气相色谱质谱均显示3-羟基丁酸、2-甲基-3-羟基丁酸、甲基巴豆酰甘氨酸-1、3-甲基巴豆酰甘氨酸-1明显增高,二羧酸轻微升高;血串联质谱仪分析结果均显示,C5∶1、C5-OH、C4-OH升高。例3,为例1和例2同胞姐姐,5月龄时因严重代谢性酸中毒住院治疗。3例患儿行ACAT1基因检测均为复合杂合突变,c.622 CT(p R208X)和c.653 CT(p S218F)。结论对于以酸中毒为突出表现的患儿,需警惕T2缺乏症,及时行尿气相色谱质谱和血串联质谱分析,以早期诊断和治疗。     

Magnetic resonance imaging in retinoblastoma and retinocytoma: a case report

Magnetic resonance imaging (MRI) is playing a growing role in the evaluation of ocular and orbital tumors. We report the case of a 26-month-old child presenting an undifferentiated retinoblastoma with a differentiated retinocytoma component in his left eye. After the eye was enucleated, we could correlate the clinicopathologic findings with the MRI scans. Both the undifferentiated retinoblastoma and the differentiated retinocytoma components could be determined on magnetic resonance imaging. Because different levels of metabolic activity within a tumor mass may influence largely T1 and T2 parameters, accurate determination of these values may be useful in determining the differentiation of a retinoblastoma, enabling a better therapeutic approach and assessment of the response to treatment.     

己糖激酶缺乏症 1 例报告并文献复习

目的探讨己糖激酶缺乏症的临床特点及基因变化。方法回顾分析1例己糖激酶缺乏症患儿的临床资料,并进行相关文献复习。结果男性患儿,6个月,临床表现为新生儿期高胆红素血症、非球形红细胞溶血性贫血、网织红细胞升高等。基因检查发现HK1存在2个杂合突变位点c.995+5GA(内含子12)和c.2216GC(外显子20);患儿父母均为复合杂合突变,c.995+5GA来自父亲,c.2216GC来自母亲。文献检索已有报道的32例患者,多表现为出生时贫血、新生儿黄疸及肝脾肿大,基因检测以HK1基因外显子和内含子核苷酸点突变为主。结论本例患儿为中国首例经基因检测确诊的已糖激酶缺乏症。临床疑似己糖激酶缺乏症时,应尽早进行基因检测。     

天冬酰胺合成酶缺乏症1例报告并文献复习

目的探讨天冬酰胺合成酶缺乏症(ASNSD)的临床及基因变异特征。方法分析1例ASNSD患儿的临床资料,并复习相关文献。结果患儿女性,5岁3月龄,主要表现为严重的精神运动发育迟缓、反复癫痫发作。头颅磁共振提示幕上脑室扩张,脑萎缩,胼胝体菲薄。全外显子测序显示患儿ASNS基因存在复合杂合变异,分别为源自父亲的整码变异c.1503_1505delAGC,及母亲的错义变异c.776G>C。该变异为首次报道,生物信息学软件(Provean、mutationtaster)均预测其致病。结论基因检测有助于ASNSD诊断,该例患儿扩充了ASNSD的基因变异谱。     

Magnetic resonance imaging of the neonatal brain

Neonatal magnetic resonance (MR) imaging is rapidly becoming the preferred modality for the evaluation of central nervous system disorders in the newborn. Recent literature supports the value of this imaging technique in diagnosing ischemic, hemorrhagic and infectious disease processes in the premature and full-term neonatal brain. Recent data in premature newborns with neurological injury also suggest a role for MR imaging in determining long-term neurodevelopmental outcomes. This review article provides a framework and overview on neonatal MR imaging techniques and examines the literature or radiological disease patterns and prognostic implications in common neurological disorders.     

NBAS 基因缺陷症一家系报告及文献复习

目的探讨NBAS基因缺陷症的发病机制及其诊断和治疗。方法回顾分析一家系2例NBAS基因缺陷症患儿的临床资料。结果先证者为14岁6月龄男性患儿,其妹妹7岁11月龄,2例患儿均有早老面容、视神经萎缩、色盲、身材矮小、肝功能异常等。血涂片均有Pelger-Hu?t细胞。基因检测示2例患儿均存在NBAS基因变异c.5752AC和c.1599+1GC,分别来自其父母。其中c.5752AC变异已有文献报道,c.1599+1GC变异为新剪切突变。随着年龄增长,未经特殊治疗,兄妹的肝功能均有明显好转。结论 NBAS基因缺陷症主要累及视神经、肝脏、骨骼等,确诊需依靠基因检测,目前无特异治疗方法。     

Magnetic resonance imaging of acute cerebellar ataxia: Report of a case with gadolinium enhancement and review of the literature

Abstract A 10-year-old girl exhibited severe cerebellar ataxia following acute enterocolitis, and was diagnosed as having acute cerebellar ataxia (ACA). MR1 of the brain in the acute stage revealed moderate swelling of the cerebellum and abnormal signal intensity enhanced with gadolinium in the cerebellar hemisphere. This is the first report of an ACA case with positive gadolinium enhancement. Cases of ACA with MRI abnormalities are reviewed and the clinical entity of ACA is discussed in association with autoimmune encephalitis,     

Megalourethra: a report of four cases and review of the literature

Megalourethra is a rare congenital anomaly characterized by severe dilatation of the penile urethra. Four cases of congenital megalourethra were seen at Sir Padampat Mother and Child Health Institute, Jaipur, during the last 10 years. Three cases of scaphoid megalourethra had no other associated congenital anomalies and were treated successfully without any complications, while one patient with a fusiform megalourethra had severe associated congenital anomalies and died. These cases are reported with a review of the literature.     

Magnetic resonance imaging of preterm brain injury

Magnetic resonance imaging (MRI) has proved to be a valuable tool for monitoring development and pathology in the preterm brain. This imaging modality is useful for assessing numerous pathologies including periventricular leukomalacia, intraventricular haemorrhage/germinal layer haemorrhage, and periventricular haemorrhagic infarction, and can help to predict outcome in these infants. MRI has also allowed the detection of posterior fossa lesions, which are not easily seen with ultrasound. Additionally, and perhaps most relevant, quantitative MR studies have shown differences between the normal appearing preterm brain at term equivalent age and term born infants, confirming that the brain develops differently in the ex utero environment. Further studies using quantifiable MR techniques will improve our understanding of the effects of the ex utero environment, including aspects of neonatal intensive care on the developing brain.