A scoring system predicting the clinical course of CLPB defect based on the foetal and neonatal presentation of 31 patients
A scoring system predicting the clinical course of CLPB defect based on the foetal and neonatal presentation of 31 patients
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DOI：
10.1007/s10545-017-0057-z
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发表时间：
2017-11-01
影响因子：
4.2
通讯作者：
Wortmann, Saskia B.
中科院分区：
文献类型：
--
作者：
Pronicka, Ewa;Ropacka-Lesiak, Mariola;Wortmann, Saskia B.
最近，CLPB缺乏症已被证明可引起遗传综合征，包括白内障、中性粒细胞减少症和3-甲基戊烯二酸尿症。令人惊讶的是，神经系统表现的范围从完全不受影响的患者到几乎没有发育的患者。经常报告肌肉张力过低和张力过高、运动障碍和进行性脑萎缩。我们介绍了31例患者的胎儿、胎儿和新生儿特征，其中5例以前未报道，使用新开发的临床严重程度评分系统对临床、代谢、影像学和其他结果进行评分，并按发病年龄加权。我们的数据通过胎儿和新生儿视频进行说明。患者被分类为具有轻度（n = 4）、中度（n = 13）或重度（n = 14）疾病表型。严重亚型最显著的特征是新生儿缺乏自主运动，并伴有呼吸机依赖和过度兴奋。胎儿和新生儿的表现反映了生存期（轻度组的当前中位年龄为17.5岁，重度组的中位死亡年龄为35天）、严重程度和所有评价结果的发病年龄方面的病程。在无自主运动、呼吸功能不全和吞咽问题的新生儿中应考虑CLPB缺乏症，特别是如果与3-甲基戊烯二酸尿症、中性粒细胞减少症和白内障相关。作为一个重要的鉴别诊断过度kperekplexia（夸张的惊吓反应），我们建议进行尿有机酸分析，血细胞计数和眼科检查，这些患者。CLPB缺乏症的新生儿表现可预测以后的病程，这对咨询极为重要。
Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely unaffected to patients with virtual absence of development. Muscular hypo- and hypertonia, movement disorder and progressive brain atrophy are frequently reported. We present the foetal, peri- and neonatal features of 31 patients, of which five are previously unreported, using a newly developed clinical severity scoring system rating the clinical, metabolic, imaging and other findings weighted by the age of onset. Our data are illustrated by foetal and neonatal videos. The patients were classified as having a mild (n = 4), moderate (n = 13) or severe (n = 14) disease phenotype. The most striking feature of the severe subtype was the neonatal absence of voluntary movements in combination with ventilator dependency and hyperexcitability. The foetal and neonatal presentation mirrored the course of disease with respect to survival (current median age 17.5 years in the mild group, median age of death 35 days in the severe group), severity and age of onset of all findings evaluated. CLPB deficiency should be considered in neonates with absence of voluntary movements, respiratory insufficiency and swallowing problems, especially if associated with 3-methylglutaconic aciduria, neutropenia and cataracts. Being an important differential diagnosis of hyperekplexia (exaggerated startle responses), we advise performing urinary organic acid analysis, blood cell counts and ophthalmological examination in these patients. The neonatal presentation of CLPB deficiency predicts the course of disease in later life, which is extremely important for counselling.