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The clinical spectrum of X-linked adrenoleukodystrophy: from Addison’s-only in men to middle-age neurologic manifestations in women

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Abstract

X-linked adrenoleukodystrophy (X-ALD) is caused by a mutation in the ABCD1 gene which encodes for a peroxisomal very long-chain fatty acid (VLCFA) transporter. Clinically, X-ALD can present a wide range of phenotypes, from slowly progressive myelopathy to rapid demyelination of brain white matter (cerebral X-ALD—CALD). Adrenocortical insufficiency (AI) occurs mainly in the pediatric age group, and it can be the first manifestation of the disease. Female carriers may also develop manifestations of myelopathy, but later in life. We present two cases of patients who show the heterogeneous clinical manifestations of X-ALD. Case 1 was a man with AI diagnosed at 6 years old and with the first manifestations of myelopathy at 44 years old, which led to the diagnosis of X-ALD. At 47 years, he developed rapidly progressive CALD. Case 2 was a woman with progressive spastic gait disturbance that started at 49 years old. The diagnosis of X-ALD was confirmed at 54 years old after the discovery of a family history of the disease. Mild progression of the neurologic manifestations was noted, but with no signs of AI nor CALD. She is currently 60 years old and under surveillance. We review the current knowledge on X-ALD as concerns its genetic and pathophysiological mechanisms, clinical presentations, diagnosis, treatment, and follow-up. This condition is a real diagnostic challenge. The early detection of AI and CALD, potentially life-threatening complications in men, is very difficult. The surveillance of these complications in female patients still raises controversy.

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Acknowledgements

The authors thank Dr. João Durães (Neurology Department, Centro Hospitalar e Universitário de Coimbra) for his critical review of the manuscript.

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Authors and Affiliations

  1. Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra, EPE, Coimbra, Portugal

    Lúcia Fadiga, Miguel Melo, Joana Saraiva & Isabel Paiva

  2. Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Miguel Melo & Joana Saraiva

Authors
  1. Lúcia Fadiga
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  2. Miguel Melo
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  3. Joana Saraiva
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  4. Isabel Paiva
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Contributions

LF, JS, and MM were involved in the conception and design of the work. LF produced the manuscript drafting and literature review. JS and MM assisted in the production of the manuscript and were also involved in the care of the patients. IP oversaw the creation of the manuscript and was involved in the care of the patients. All the authors approved publication of the final version.

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Correspondence to Lúcia Fadiga.

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The local institute’s committee approved this study.

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Informed consent for publication was obtained from the closest relative of patient 1 and from patient 2.

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The authors declare no competing interests.

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Fadiga, L., Melo, M., Saraiva, J. et al. The clinical spectrum of X-linked adrenoleukodystrophy: from Addison’s-only in men to middle-age neurologic manifestations in women. Hormones 21, 33–40 (2022). https://doi.org/10.1007/s42000-021-00325-y

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  • DOI: https://doi.org/10.1007/s42000-021-00325-y

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