Fumarate hydratase deficiency
Fumarate hydratase deficiency
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DOI：
10.1023/a:1005379330187
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发表时间：
1998-06-01
影响因子：
4.2
通讯作者：
Bellini, C
中科院分区：
文献类型：
--
作者：
Bonioli, E;Di Stefano, A;Bellini, C
* 通信：Istituto di Clinica Pediatrica dell $> Universita，Largo G. Gaslini，5，16147热那亚，意大利组织含有线粒体和胞质形式的延胡索酸水合酶人或延胡索酸水合酶（EC 4.2. 1.2）。这两种亚型由位于人类1号染色体上的相同常染色体基因编码，但氨基末端残基不同。大脑是个例外，因为它只含有线粒体同工酶。到目前为止，已在11例患者中描述了脱氢酶（McKusick 136850）的缺失（Narayanan et al 1996和其中的参考文献）。在所有患者中均发现了与大脑相关的临床和病理特征，而面部畸形和肝脏疾病仅在一名患者中描述。神经功能损害的严重程度是相当可变的，临床过程可以是静态的或在生命的前2年内致命的。结果的这种差异与残留酶活性水平或不同的组织受累无关。我们描述了一个新的病人的临床和生化结果与酶缺乏症。先证者在怀孕36周后通过剖腹产出生。无关的父母和一个哥哥（3岁）是健康的。出生体重为2670 g，头围为34.5 cm（均为第50百分位数）。APGAR评分为4/7。出生后5天，全身张力减退明显，深腱反射减退，喉喘鸣明显，患者因吸吮和吞咽困难需要管饲。在1月龄时进行的脑部CT扫描显示大脑室和扩大的蛛网膜下腔。1个月后，MRI证实脑室和蛛网膜下腔扩大，T2加权像显示脑室周围白色物质信号增强。我们在病人4个月大时检查了他。他的体重为4240克，身长为58厘米，头围为36厘米（均低于第3百分位数）。他看起来情况很差，仍然需要管饲。肝脏大小和硬度正常。神经系统检查显示没有头部控制，明显的张力减退和全面的精神发育迟滞。视力和随访均不存在。患者表现为阵挛性运动、肌张力亢进和反张性姿势。脑电图呈典型的高血压样改变。脑干听觉诱发电位严重异常。喉镜检查显示右声带麻痹。
* Correspondence: Istituto di Clinica Pediatrica dellœUniversita, Largo G. Gaslini, 5, 16147 Genova, Italy tissues contain a mitochondrial and a cytosolic form of fumarate hydratase Human or fumarase (EC 4.2. 1.2). The two isoforms are encoded by the same autosomal gene localized on chromosome 1 in humans and di† er in the amino-terminal residue. The brain is an exception since it only contains the mitochondrial isoenzyme. De–ciency of fumarase (McKusick 136850) has so far been described in 11 patients (Narayanan et al 1996 and references therein). Clinical and pathological features related to the brain were found in all patients, while facial dysmorphism and a liver disorder have only been described in one. The severity of neurological impairment is quite variable and the clinical course can be static or fatal within the–rst 2 years of life. This di† erence in outcome has not been correlated with the level of residual enzyme activity or with di† erential tissue involvement. We describe clinical and biochemical–ndings in a new patient with fumarase de–ciency. The propositus was born by caesarean section after 36 weeks of gestation. The unrelated parents and an older brother (3 years of age) were healthy. Birth weight was 2670g and head circumference was 34.5 cm (both at 50th centile). APGAR score was 4/7. Five days after birth, generalized hypotonia was evident, deep tendon re—exes were hypoactive, laryngeal stridor was evident and the patient needed tube feeding because of sucking and swallowing difficulties. Brain CT scan performed at 1 month of age showed large cerebral ventricles and enlarged subarachnoid spaces. One month later, MR imaging con–rmed the enlargement of ventricles and subarachnoid spaces and showed an increased signal intensity in the periventricular white matter on T2-weighted images. We examined the patient at the age of 4 months. His weight was 4240g, length was 58cm and head circumference was 36 cm (all below 3rd centile). He appeared to be in quite poor condition and still needed tube feeding. Liver size and consistency were normal. Neurological examination demonstrated no head control, marked hypotonia and global psychomotor retardation. Both visual–xation and following were absent. The patient presented seizures characterized by clonic movements, hypertonia and opisthotonic posturing. EEG showed a typical hypsarrhythmic pattern. Brainstem auditory evoked potentials were severely abnormal. Laryngoscopic examination demonstrated paralysis of the right vocal cord.