Low donor chimerism may be sufficient to prevent demyelination in adrenoleukodystrophy.
Low donor chimerism may be sufficient to prevent demyelination in adrenoleukodystrophy.
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DOI：
10.1002/jmd2.12259
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Yamagata T
中科院分区：
文献类型：
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作者：
Ikeda T;Kawahara Y;Miyauchi A;Niijima H;Furukawa R;Shimozawa N;Morimoto A;Osaka H;Yamagata T
肾上腺脑白质营养不良（ALD）是一种过氧化物酶体疾病，其特征是由三磷酸腺苷结合盒亚家族D成员1（ABCD 1）基因突变引起的白色变性，导致极长链脂肪酸（VLCFA）蓄积。造血干细胞移植（HSCT）是最有效的治疗方法;然而，防止脱髓鞘进展所需的供体与受体细胞的比例尚不清楚。根据临床表型、血浆VLCFA水平升高和致病性ABCD 1突变c.293C>T（p.Ser98Leu），先证者在5岁时被诊断为儿童脑型ALD。诊断后不久，他就卧床不起。在1岁时，他的弟弟被发现携带相同的ABCD 1突变;尽管没有症状，但在1岁零9个月时，头部磁共振成像（MRI）显示大脑白色物质中的高信号强度病变。该患者接受了非亲缘脐带血移植（UCBT），采用了减少的预处理方案，导致混合嵌合体。UCBT后7年，外周血和脑脊液中供者嵌合率仍较低（<10%）。然而，即使没有进行第二次HSCT，他的神经系统症状和脑部MRI结果也没有恶化。我们的病例表明，即使是少量的供体细胞也可以防止ALD的脱髓鞘。在考虑第二次HSCT的时机时，这是一个重要的情况。
Adrenoleukodystrophy (ALD) is a peroxisomal disorder characterized by white matter degeneration caused by adenosine triphosphate‐binding cassette subfamily D member 1 (ABCD1) gene mutations, which lead to an accumulation of very‐long‐chain fatty acids (VLCFA). Hematopoietic stem cell transplantation (HSCT) is the most effective treatment; however, the ratio of donor‐to‐recipient cells required to prevent the progression of demyelination is unclear. The proband was diagnosed with the childhood cerebral form of ALD at 5 years of age based on the clinical phenotype, elevated plasma VLCFA levels, and pathogenic ABCD1 mutation c.293C>T (p.Ser98Leu). Soon after the diagnosis, he became bedridden. At 1 year of age, his younger brother was found to carry the same ABCD1 mutation; despite being asymptomatic, at 1 year and 9 months, head magnetic resonance imaging (MRI) showed high‐signal‐intensity lesions in the cerebral white matter. The patient underwent unrelated cord blood transplantation (UCBT) with a reduced conditioning regimen, which resulted in mixed chimerism. For 7 years after UCBT, the donor chimerism remained low (<10%) in peripheral blood and cerebrospinal fluid. However, even though a second HSCT was not performed, his neurological symptoms and brain MRI findings did not deteriorate. Our case suggests that even a small number of donor cells may prevent demyelination in ALD. This is an important case when considering the timing of a second HSCT.