Low donor chimerism may be sufficient to prevent demyelination in adrenoleukodystrophy

<jats:title>Abstract</jats:title><jats:p>Adrenoleukodystrophy (ALD) is a peroxisomal disorder characterized by white matter degeneration caused by adenosine triphosphate‐binding cassette subfamily D member 1 (<jats:italic>ABCD1</jats:italic>) 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 <jats:italic>ABCD1</jats:italic> 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 <jats:italic>ABCD1</jats:italic> 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.</jats:p>