Brain-sparing cord blood transplantation for the borderline stage of adrenoleukodystrophy

Yutaro Yada; Michiko Torio; Yuhki Koga; Fumiya Yamashita; Takuya Ichimura; Katsuhide Eguchi; Masataka Ishimura; Yuichi Mushimoto; Akio Hiwatashi; Momoko Sasazuki; Ryutaro Kira; Yasunari Sakai; Shouichi Ohga

doi:10.1016/j.ymgmr.2021.100778

Brain-sparing cord blood transplantation for the borderline stage of adrenoleukodystrophy

Mol Genet Metab Rep. 2021 Jun 24:28:100778. doi: 10.1016/j.ymgmr.2021.100778. eCollection 2021 Sep.

Authors

Affiliations

¹ Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
² Department of Pediatric Neurology, Fukuoka Children's Hospital, Fukuoka 813-0017, Japan.
³ Department of Pediatrics, Yamaguchi University, Ube 755-8505, Japan.
⁴ Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Abstract

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.

Keywords: ALD, Adrenoleukodystrophy; ASD, autism spectrum disorder; Adrenoleukodystrophy; Brain-sparing irradiation; CBT, cord blood transplantation; GVHD, graft failure and graft-versus-host disease; HCT, hematopoietic cell transplantation; HDC, hydrocortisone; HLA, human leukocyte antigen; Hematopoietic cell transplantation; Loes score; Reduced-intensity conditioning; VLCFA, very long-chain saturated fatty acids.

Publication types

Case Reports