Low donor chimerism may be sufficient to prevent demyelination in adrenoleukodystrophy. Issue 1 (17th November 2021)

• Record Type: Journal Article
• Authors: Ikeda, Takahiro; Kawahara, Yuta; Miyauchi, Akihiko; Niijima, Hitomi; Furukawa, Rieko; Shimozawa, Nobuyuki; Morimoto, Akira; Osaka, Hitoshi; Yamagata, Takanori
• Is Part Of: JIMD reports. Volume 63:Issue 1(2022)
• Page Start: 19
• Page End: 24
• Publication Date: 2021-11-17
• Subjects: ATP‐binding cassette subfamily D member 1 -- cerebral adrenoleukodystrophy -- cerebrospinal fluid -- hematopoietic stem cell transplantation -- unrelated cord blood transplantation -- very‐long‐chain fatty acids; Metabolism, Inborn errors of -- Periodicals; Metabolism -- Disorders -- Periodicals; 616.39042
• DOI: 10.1002/jmd2.12259
• Languages: English
• ISSNs: 2192-8304

Abstract

Abstract: 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.