X-连锁肾上腺脑白质营养不良产前诊断探讨

目的探讨X-连锁肾上腺脑白质营养不良(adrenoleukodystrophy,ALD)产前诊断的方法。方法应用气相色谱-质谱联用法对17例ALD高危孕妇进行了18次羊水细胞中极长链脂肪酸(very long chain fatty acids,VLCFAs)水平测定,其中8例胎儿出生后或引产后进行了血浆VLCFAs水平检测。应用PCR和测序方法对8例胎儿羊水细胞或生后外周血细胞DNA进行了基因突变分析(其中4例羊水细胞VLCFAs水平增高,4例VLCFAs正常)。应用Western杂交对同一家系的两例胎儿羊水细胞进行了ALD蛋白(ALD protein,ALDP)的检测(两例胎儿VLCFAs均增高,1例女性,1例男性)。结果18例胎儿中,11例羊水细胞VLCFAs水平正常,7例增高(3例男性,4例女性)。8例胎儿出生后或引产后血浆VLCFAs水平检测,3例增高,5例正常,与产前诊断结果相一致。其中4例羊水细胞VLCFAs水平增高的胎儿,均有ABCD1基因突变,4例羊水细胞VLCFAs水平正常者,均未发现突变。VLCFAs增高的男性胎儿,未检测到ALDP,VLCFAs增高的女性胎儿,可检测到ALDP。结论羊水细胞中VLCFAs水平检测可以准确地进行X-ALD产前诊断,结合基因突变分析及ALDP的测定,可进一步保证产前诊断的准确性。

Prenatal diagnosis of X-linked adrenoleukodystrophy

Objective To make prenatal dignosis of X-linked adrenoleukodystrophy (ALD) for the prevention of the disease. Methods Eighteen amniocenteses were performed on 17 suspected carriers of X-ALD during 18-30 gestation weeks. The very long chain fatty acids (VLCFAs) levels of cultured amniocytes were tested by gas chromatography-mass spectrometry (GC/MS). The plasma VLCFAs levels were measured in 8 of the 18 prenatal diagnosed children when they were born or after abortion. ABCD1 gene mutation analysis was carried out in 8 cases by PCR and sequencing. ALDP of amniocytes was tested by Western blotting in 2 cases from a family, one female, another male, and the VLCFAs of cultured amniocytes were increased in both of them. Results Among the 18 fetuses, 10 were males and 8 were females. The VLCFAs levels of the cultured amniocytes were increased in 3 males and 4 females. The postnatal plasma VLCFAs were normal in 5 cases with normal VLCFAs levels of amniocytes, and increased in 3 cases with high VLCFAs levels of amniocytes. ABCD1 gene mutations were found in 4 cases with high VLCFAs levels of amniocytes, no mutation was found in other 4 cases with normal VLCFAs levels of amniocytes. ALDP of amniocytes could be detected in the female with high VLCFAs levels of amniocytes, and it could not be detected in the male with high VLCFAs levels of amniocytes. Three male fetuses with high VLCFAs levels of amniocytes were aborted. The others who were born were normal clinically so far. Conclusion The prenatal diagnosis is very important for the prevention of ALD. Amniocyte VLCFAs level analysis combined with ABCD1 gene mutation analysis and ALDP test could make a proper prenatal diagnosis.