X连锁肾上腺脑白质营养不良新生儿筛查与早期干预的意义、现状与展望

doi:10.12372/jcp.2026.26e0502

Abstract

Abstract:

X-linked adrenoleukodystrophy (X-ALD) is a severe, progressive peroxisomal disorder inherited in an X-linked recessive pattern, characterized by high morbidity, neurologic deterioration, and premature mortality. Early identification and timely initiation of presymptomatic intervention are crucial for improving patient outcomes. Currently, newborn screening for X-ALD has been widely implemented internationally. In recent years, some provinces and cities in China have begun exploring the inclusion of X-ALD in routine newborn screening programs, leveraging advanced mass spectrometry platforms, but a standardized screening protocol has yet to be established. This article systematically reviews the clinical features of X-ALD, early intervention strategies, the value of newborn screening, and international and domestic practices and challenges. It highlights the necessity of X-ALD screening and identifies key issues requiring urgent resolution at this stage, aiming to provide scientific evidence and insights for developing and promoting standardized screening and early intervention protocols tailored to the Chinese population.

Key words: X-linked adrenoleukodystrophy, newborn screening, peroxisomal disorder, practical path

CLC Number:

YANG Xin, CHEN Chi, YANG Rulai. Newborn screening and early intervention for X-linked adrenoleukodystrophy: significance, current status, and future perspectives[J].Journal of Clinical Pediatrics, 2026, 44(8): 675-681.

Figures/Tables 2

Table 1

Table 2

Biomarker screening methods for X-ALD in different countries or regions"

国家/地区	一级筛查			二级筛查			说明
国家/地区	筛查方法	筛查指标	切值	筛查方法	筛查指标	切值	说明
美国纽约州^[13]	MS/MS	C26:0-LPC	未公布	HPLC-MS/MS	C26:0-LPC	未公布
荷兰^[22]	FIA- MS/MS	C26:0-LPC	≥0.32μmol/L	HPLC-MS/MS	C26:0-LPC	≥0.15μmol/L	对一级筛查阳性新生儿进行X染色体数量检测，仅对其中男性新生儿进行二级筛查
中国台湾^[17]	FIA- MS/MS	C26:0-LPC	≥0.3μmol/L	LC-MS/MS	C26:0-LPC	≥0.3μmol/L
日本^[23]	HPLC-MS/MS	C26:0-LPC，C24:0-LPC	未公布	HPLC-MS/MS	C26:0-LPC，C24:0-LPC	未公布	一级筛查阳性重新采集干血斑行二级筛查
意大利^[24]	FIA- MS/MS	C20:0-LPC，C22:0-LPC，C24:0-LPC，C26:0-LPC，C20，C22，C24，C26	C26:0-LPC≥0.5μmol/L （CLIR分析）	UHPLC-MS/MS	C26:0-LPC，C26	C26:0-LPC>0.1μmol/L
美国加利福尼亚州^[25]	FIA- MS/MS	C26:0-LPC	≥0.42μmol/L	LC-MS/MS	C26:0-LPC	≥0.22μmol/L	二级筛查切值起初为≥0.15μM，后调整为≥0.22μM
美国明尼苏达州^[26]	LC-MS/MS	C26:0-LPC	阳性：≥0.3μmol/L；临界值：0.16~0.29μmol/L	LC-MS/MS	C26:0-LPC	≥0.16μmol/L	一级筛查阳性直接召回行诊断性检查，位于临界范围者重新采集干血斑行二级筛查。
美国伊利诺伊州^[27]	LC-MS/MS	C26:0-LPC	阳性：≥0.28μmol/L；临界值：0.18~0.27μmol/L	LC-MS/MS	C26:0-LPC	阳性：≥0.28μM；临界值：0.18~0.27μmol/L	一级筛查阳性原血片复查仍为阳性则直接召回行诊断性检查。位于临界范围者重新采集干血斑行二级筛查。两次检测结果不一致或C24:0-LPC<0.02μM视为无效样本，重新采样。
美国佐治亚州^[28]	FIA- MS/MS	C20:0-LPC，C22:0-LPC，C24:0-LPC，C26:0-LPC及其比值	CLIR分析判定阳性	LC-MS/MS	C26:0-LPC	>0.3μmol/L	一级筛查检测结果利用CLIR结合年龄调整的参考范围和确诊病例数据，生成综合评分，评分高于确诊病例评分分布的1%分位数即为阳性
美国北卡罗来纳州^[29]	LC-MS/MS	C26:0-LPC，C24:0-LPC	C26:0-LPC≥0.08μmol/L或C24:0-LPC≥0.175μmol/L	LC-MS/MS （原血片复查）	C26:0-LPC，C24:0-LPC	C26:0-LPC平均值在0.08-0.15 μmol/L之间伴C24:0-LPC≥0,175 μmol/L或C26:0-LPC平均值≥0,15 μmol/L
美国宾夕法尼亚州、内布拉斯加州^[30-31]	FIA- MS/MS	C26:0-LPC	>0.36μmol/L	LC-MS/MS	C26:0-LPC	>0.15μmol/L	二级筛查阳性重新采集干血斑复查二级检测
中国广东省^[37]	LC-MS/MS	C26:0-LPC	≥0.17μmol/L				初次检测及原血片复查均高于切值即判定为阳性，予以召回行基因检测，未进行二级筛查

Table 2

References 40

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分型	占比/%	发病年龄	主要临床表现
儿童脑型ALD	31~35	3~10岁，高峰期为7岁	进行性行为和认知障碍；运动能力倒退；炎症性脑脱髓鞘病变；绝大多数有PAI表现；进展迅速，通常在发病后2~4年陷入植物状态或死亡
青少年脑型ALD	4~7	11~21岁	与儿童型相似，进展速度相对缓慢
成人脑型ALD	2~5	>21岁	痴呆、行为障碍和局灶性神经功能障碍；病程与儿童型相似
AMN	40~46	20~40岁	进行性痉挛性截瘫、感觉性共济失调、括约肌功能障碍。大部分合并有PAI；大多数情况下进展缓慢；40%~45%患者伴随脑部MRI异常表现
单纯Addison病型	10	2岁~成年，最常见于7.5岁	PAI，无明显的神经系统受累
无症状型	随年龄增长而减少		存在生化和基因异常，但无肾上腺功能不全和神经系统受累表现
杂合子型	—	高度异质性，大多>40岁	指女性携带者；65%的女性携带者60岁后出现AMN症状；脑部受累（2%）和PAI（1%）罕见

Newborn screening and early intervention for X-linked adrenoleukodystrophy: significance, current status, and future perspectives

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