In this issue of the Journal of Human Genetics, Shimozawa et al.1 describe a comprehensive diagnostic and follow-up system for X-linked adrenoleukodystrophy (X-ALD) in Japan. The authors present a number of mutation types in the causative ABCD1 gene in Japanese patients, and propose that the genetic testing should be used not only for diagnosis in patients with symptoms but also for a presymptomatic diagnosis in at-risk individuals, as an effective therapy, namely hematopoietic stem cell transplantation (HSCT), is available for this disease. The system proposed by the authors, which consists of metabolic and genetic testing, genetic counseling, therapy and a longitudinal follow-up, will be a model for a genetic disease with effective therapy.

X-ALD is a neurodegenerative disorder associated with the accumulation of very long-chain saturated fatty acids (VLCFAs), and it has several clinical forms, including childhood cerebral form, adrenomyeloneuropathy and Addison's disease (adrenal insufficiency).2 Patients are usually male, but some carrier females also develop mild neurological manifestations. The diagnosis of X-ALD is made in combination with clinical findings, brain magnetic resonance imaging, plasma concentration of VLCFAs and molecular genetic testing of ABCD1.3 X-ALD is inherited in an X-linked manner: 93% of the X-ALD cases are caused by the ABCD1 mutation inherited from one parent and the remaining 7% are caused by a de novo mutation. Corticosteroid replacement therapy for adrenal insufficiency and HSCT are effective.4, 5

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