Molecular Genetics and Metabolism Reports ( IF 1.9 ) Pub Date : 2021-06-24 , DOI: 10.1016/j.ymgmr.2021.100778 Yutaro Yada 1 , Michiko Torio 1 , Yuhki Koga 1 , Fumiya Yamashita 2 , Takuya Ichimura 1, 3 , Katsuhide Eguchi 1 , Masataka Ishimura 1 , Yuichi Mushimoto 1 , Akio Hiwatashi 4 , Momoko Sasazuki 1 , Ryutaro Kira 2 , Yasunari Sakai 1 , Shouichi Ohga 1
Background
Adrenoleukodystrophy (ALD) is an X-linked disorder characterized by rapidly progressive deterioration of neurocognitive functions and premature death. In addition to the difficulty in identifying the earliest signs of ALD, treatment-associated exacerbation of neurological symptoms has been an obstacle to achieve successful hematopoietic cell transplantation (HCT) for affected children.
Case report
We report a 9-year-boy with ALD. He presented with impairment in social skills compatible to the diagnosis of autism spectrum disorder from 3 years of age. He showed progressive strabismus, slurred speech and dysmetria at 6 years of age. The head MRI showed symmetrical T2-hyperintense lesions in the occipital white matters with a gadolinium enhancement, which extended to the internal capsules. The Loes score was thus calculated as 13. Very-long-chain-fatty-acids were increased to 1.800 (C24:0/C22:0) and 0.077 (C26:0/C22:0) in leukocytes. Sanger sequencing confirmed the pathogenic variant in ABCD1 (NM_000033.4:p.Gly512Ser). After multidisciplinary discussions over the treatment options, we performed a cord blood HCT with a reduced intensity conditioning (fludarabine, melphalan and brain-sparing total body irradiation). He was fully recovered with >90% chimerism of donor leukocytes at 55 days after HCT. He experienced three times of generalized seizures after discharge, that has been well controlled for 2 years without other complications or neurocognitive deteriorations.
Conclusion
For patients with ALD on a borderline indication for HCT, brain-sparing irradiation might be an alternative option in reduced intensity conditioning. Careful decision-making process and tailored conditioning are critical for the successful outcome of HCT for children with ALD.
中文翻译:
肾上腺脑白质营养不良临界期的留脑脐带血移植
背景
肾上腺脑白质营养不良 (ALD) 是一种 X 连锁疾病,其特征是神经认知功能快速进行性恶化和过早死亡。除了难以识别 ALD 的最早迹象外,与治疗相关的神经系统症状恶化一直是受影响儿童成功进行造血细胞移植 (HCT) 的障碍。
案例报告
我们报告一名患有 ALD 的 9 岁男孩。他从 3 岁起就出现与自闭症谱系障碍诊断相符的社交技能障碍。他在 6 岁时表现出进行性斜视、言语不清和视力障碍。头部 MRI 示枕部白质对称性 T2 高信号病灶伴钆强化,并延伸至内囊。因此,Loes 得分计算为 13。白细胞中的超长链脂肪酸增加到 1.800 (C24:0/C22:0) 和 0.077 (C26:0/C22:0)。Sanger测序证实了ABCD1的致病变异(NM_000033.4:p.Gly512Ser)。在对治疗方案进行多学科讨论后,我们进行了脐带血 HCT,并降低了强度调节(氟达拉滨、美法仑和保留大脑的全身照射)。在 HCT 后 55 天,他完全康复,供体白细胞嵌合体 >90%。出院后3次全身性癫痫发作,2年控制良好,无其他并发症或神经认知功能下降。
结论
对于处于 HCT 临界适应症的 ALD 患者,保留脑部照射可能是降低强度调节的替代选择。谨慎的决策过程和量身定制的条件对 ALD 儿童 HCT 的成功结果至关重要。