X-连锁肾上腺脑白质营养不良(X-linked adrenoleukodystrophy,X-ALD)是一种编码过氧化物酶体跨膜蛋白三磷酸腺苷结合盒亚家族D成员1(adenosine 5′-triphosphate binding cassette subfamily D member 1,ABCD1)基因突变的遗传病,其具有...X-连锁肾上腺脑白质营养不良(X-linked adrenoleukodystrophy,X-ALD)是一种编码过氧化物酶体跨膜蛋白三磷酸腺苷结合盒亚家族D成员1(adenosine 5′-triphosphate binding cassette subfamily D member 1,ABCD1)基因突变的遗传病,其具有多种临床表现,从首发症状到致死性炎性脱髓鞘的进展过程极其快速。因此,识别早期临床症状,早诊断、早治疗能有效阻止该疾病进展。本研究报道1例少见的以“皮肤色素沉着3年”为唯一临床表型的X-ALD患者的实验室检查及影像学特点,并采用高通量测序为患者及其父母进行ABCD1基因测序。实验室检查结果提示患者肾上腺皮质功能减退,血清极长链脂肪酸浓度增高;肾上腺及脑MRI显示未见明显异常信号影。患者基因检测结果显示ABCD1基因外显子1发生c.521A>C半合子突变,其母亲为同位点杂合突变,故诊断为“X-连锁肾上腺脑白质营养不良”。随访过程中,患者肾上腺皮质功能不全症状没有改善,颅脑MRI显示右侧放射冠、左侧顶叶脑白质见少许点状高flair信号影,提示可能出现脑损伤。仅有皮肤表现而无神经系统异常的X-ALD患者极易被忽视,早期诊断并给予早期干预是延缓该疾病进展的重要途径。因此,建议所有的男性儿童患者以皮肤色素沉着为唯一临床表现,继而诊断肾上腺皮质功能减退时,都应该进行基因检测,及早鉴别X-ALD。展开更多
Obiective:To elucidate the phenotype and the genotype-phenotype correlations in Chinese patients with X-linked adrenoleukodystrophy(X-ALD).Methods:Clinical features of 40 Chinese patients with X-ALD were studied and m...Obiective:To elucidate the phenotype and the genotype-phenotype correlations in Chinese patients with X-linked adrenoleukodystrophy(X-ALD).Methods:Clinical features of 40 Chinese patients with X-ALD were studied and mutation spectrums were investigated by polymerase chain reaction (PCR) and sequencing. Results:Among these patients, four were siblings from two unrelated families, the others were unrelated. There were 31 cases with childhood cerebral (CCALD), 8 cases with adolescent cerebral (ACALD) and 1 case with adrenomyeloneuropathy (AMN). Visual impairment, which presented in 12 cases (30%), was the most common initial symptom. Nine (69%) of 13 cases who had hydrocortisone and ACTH measured showed adrenal insufficiency. By follow-up date, 19 cases (47.5%) were dead. The interval from onset to death varied from 1 to 6 years and the average were 3.3 years. The mean age at death was 10.5 years. Eleven cases (27.5%) were in vegetable state. The mean interval from onset to apparently vegetable state was 2.8 years (range from 1 to 6 years). Four cases had progressive neurological disability. Four cases were lost follow-up. One case with CCALD and one case with ACALD progressed slowly. The courses of the disease of these two patients were 5 years and 15 years respectively. Thirty five mutations were identified in 40 cases. Most were located within exon 1-3 (40%, 16/40) and exon 6-8 (42%, 17/40). There is a distinct clustering of missense mutations in exon 6 (17%, 7/40). Five types of mutations were associated with CCALD, three with ACALD and a missense mutation was identified in the patients with AMN. The two patients with long disease courses had a missence mutation c.1559 T>A and a nonsense mutation c.1785 G>A respectively. The siblings with similar manifestations and onset age were observed in two families, whose mutations were c.887 A>G and c.1028 G>T. Conclusion:The phenotypes, disease severity and rate of neurodegeneration could not be predicted by the nature of mutations.展开更多
文摘X-连锁肾上腺脑白质营养不良(X-linked adrenoleukodystrophy,X-ALD)是一种编码过氧化物酶体跨膜蛋白三磷酸腺苷结合盒亚家族D成员1(adenosine 5′-triphosphate binding cassette subfamily D member 1,ABCD1)基因突变的遗传病,其具有多种临床表现,从首发症状到致死性炎性脱髓鞘的进展过程极其快速。因此,识别早期临床症状,早诊断、早治疗能有效阻止该疾病进展。本研究报道1例少见的以“皮肤色素沉着3年”为唯一临床表型的X-ALD患者的实验室检查及影像学特点,并采用高通量测序为患者及其父母进行ABCD1基因测序。实验室检查结果提示患者肾上腺皮质功能减退,血清极长链脂肪酸浓度增高;肾上腺及脑MRI显示未见明显异常信号影。患者基因检测结果显示ABCD1基因外显子1发生c.521A>C半合子突变,其母亲为同位点杂合突变,故诊断为“X-连锁肾上腺脑白质营养不良”。随访过程中,患者肾上腺皮质功能不全症状没有改善,颅脑MRI显示右侧放射冠、左侧顶叶脑白质见少许点状高flair信号影,提示可能出现脑损伤。仅有皮肤表现而无神经系统异常的X-ALD患者极易被忽视,早期诊断并给予早期干预是延缓该疾病进展的重要途径。因此,建议所有的男性儿童患者以皮肤色素沉着为唯一临床表现,继而诊断肾上腺皮质功能减退时,都应该进行基因检测,及早鉴别X-ALD。
文摘Obiective:To elucidate the phenotype and the genotype-phenotype correlations in Chinese patients with X-linked adrenoleukodystrophy(X-ALD).Methods:Clinical features of 40 Chinese patients with X-ALD were studied and mutation spectrums were investigated by polymerase chain reaction (PCR) and sequencing. Results:Among these patients, four were siblings from two unrelated families, the others were unrelated. There were 31 cases with childhood cerebral (CCALD), 8 cases with adolescent cerebral (ACALD) and 1 case with adrenomyeloneuropathy (AMN). Visual impairment, which presented in 12 cases (30%), was the most common initial symptom. Nine (69%) of 13 cases who had hydrocortisone and ACTH measured showed adrenal insufficiency. By follow-up date, 19 cases (47.5%) were dead. The interval from onset to death varied from 1 to 6 years and the average were 3.3 years. The mean age at death was 10.5 years. Eleven cases (27.5%) were in vegetable state. The mean interval from onset to apparently vegetable state was 2.8 years (range from 1 to 6 years). Four cases had progressive neurological disability. Four cases were lost follow-up. One case with CCALD and one case with ACALD progressed slowly. The courses of the disease of these two patients were 5 years and 15 years respectively. Thirty five mutations were identified in 40 cases. Most were located within exon 1-3 (40%, 16/40) and exon 6-8 (42%, 17/40). There is a distinct clustering of missense mutations in exon 6 (17%, 7/40). Five types of mutations were associated with CCALD, three with ACALD and a missense mutation was identified in the patients with AMN. The two patients with long disease courses had a missence mutation c.1559 T>A and a nonsense mutation c.1785 G>A respectively. The siblings with similar manifestations and onset age were observed in two families, whose mutations were c.887 A>G and c.1028 G>T. Conclusion:The phenotypes, disease severity and rate of neurodegeneration could not be predicted by the nature of mutations.
文摘肾上腺脑白质营养不良（adrenoleukodystrophy,ALD）是一组遗传性脂质代谢病,属于过氧化物酶体病范畴,其中X连锁肾上腺脑白质营养不良（Xlinked adrenoleukodystrophy,X-ALD）较为多见,与ATP结合转运子超家族成员D1（ATP binding cassette subfamily D member 1,OMIM：300100）基因突变相关,
