Early Infantile Krabbe Disease: Results of the World-Wide Krabbe Registry
Early Infantile Krabbe Disease: Results of the World-Wide Krabbe Registry
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DOI：
10.1016/j.pediatrneurol.2011.05.007
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发表时间：
2011-09-01
影响因子：
3.8
通讯作者：
Carter, Randy L.
中科院分区：
文献类型：
--
作者：
Duffner, Patricia K.;Barczykowski, Amy;Carter, Randy L.
纽约州于2006年开始筛查克拉布病，以便在症状出现前识别患有克拉布病的婴儿。由于半乳糖苷酶活性和大多数基因型都不能可靠地预测表型，因此开发了全球登记研究，以确定其他临床/神经诊断数据是否可以预测新生儿筛查人群中的早期婴儿克拉布病。病程，半乳糖苷酶活性，DNA突变，并在67个有症状的儿童早期婴儿克拉伯病的初步神经诊断研究的数据，从父母的问卷调查和医疗记录。最初的体征包括哭泣/易怒、皮质握拳和头部控制不良。半乳糖苷酶活性一致较低。17例中有8例表现出新的突变。92%（n = 25）的患者脑脊液蛋白升高，76%（n = 42）的患者磁共振成像异常，67%（n = 15）的患者计算机断层扫描异常，43%（n = 28）的患者脑电图异常，100%（n = 5）的患者神经传导速度异常，100%（n = 15）的患者神经传导速度异常。脑干诱发电位异常者占83%（n = 6），视觉诱发电位异常者占50%（n = 6）。1年、2年和3年生存率分别为60%、26%和14%。虽然大多数有症状的早期婴儿型患者表现出异常的脑脊液蛋白，磁共振成像，脑干诱发反应和神经传导速度，受影响的儿童的研究可能是正常的。需要其他生物标志物来预测新生儿筛查人群的表型。(C)2011 Elsevier Inc. All rights reserved.
New York State began screening for Krabbe disease in 2006 to identify infants with Krabbe disease before symptom onset. Because neither galactocerebrosidase activity nor most genotypes reliably predict phenotype, the World Wide Registry was developed to determine whether other clinical/neurodiagnostic data could predict early infantile Krabbe disease in the newborn screening population. Data on disease course, galactocerebrosidase activity, DNA mutations, and initial neurodiagnostic studies in 67 symptomatic children with early infantile Krabbe disease were obtained from parent questionnaires and medical records. Initial signs included crying/irritability, cortical fisting, and poor head control. Galactocerebrosidase activity was uniformly low. Eight of 17 manifested novel mutations. Ninety-two percent (n = 25) exhibited elevated cerebrospinal fluid protein; 76% (n = 42) demonstrated abnormal magnetic resonance images; 67% (n = 15) exhibited abnormal computed tomography findings; 43% (n = 28) produced abnormal electroencephalogram findings; 100% (n = 5) demonstrated abnormal nerve conduction velocities; 83% (n = 6) produced abnormal brainstem evoked responses; and 50% (n = 6) exhibited abnormal visual evoked responses. One, 2, and 3 year survivals were 60%, 26%, and 14%, respectively. Although most symptomatic patients with the early infantile phenotype manifested abnormal cerebrospinal fluid protein, magnetic resonance imaging, brainstem evoked responses, and nerve conduction velocities, studies of affected children may be normal. Other biomarkers are needed to predict phenotype in the newborn screening population. (C) 2011 Elsevier Inc. All rights reserved.