Adrenoleukodystrophy (ALD) is a peroxisomal metabolic disorder owing to mutations in ABCD1 with a highly complex clinical presentation
Presenting complaints are usually adrenal insufficiency (80% in childhood) or myelopathy (in adulthood)
Cerebral ALD can occur at any age and is most likely defined by the interplay between the primary ABCD1 mutation, a multitude of genetic variants and environmental factors
Haematopoietic stem cell transplantation (HSCT) remains the only therapeutic intervention for cerebral ALD, but the outcome of the procedure is poor unless performed at an early stage of cerebral disease
No treatment is currently available for the progressive myelopathy associated with ALD
Early diagnosis of boys with ALD by screening at birth allows the early detection of adrenal insufficiency to initiate timely adrenal steroid replacement therapy and the early detection of cerebral ALD to offer allogeneic HSCT
X-Linked adrenoleukodystrophy (ALD) is a peroxisomal metabolic disorder with a highly complex clinical presentation. ALD is caused by mutations in the ABCD1 gene, which leads to the accumulation of very long-chain fatty acids in plasma and tissues. Virtually all men with ALD develop adrenal insufficiency and myelopathy. Approximately 60% of men develop progressive cerebral white matter lesions (known as cerebral ALD). However, one cannot identify these individuals until the early changes are seen using brain imaging. Women with ALD also develop myelopathy, but generally at a later age than men and adrenal insufficiency or cerebral ALD are very rare. Owing to the multisystem symptomatology of the disease, patients can be assessed by the paediatrician, general practitioner, endocrinologist or a neurologist. This Review describes current knowledge on the clinical presentation, diagnosis and treatment of ALD, and highlights gaps in our knowledge of the natural history of the disease owing to an absence of large-scale prospective cohort studies. Such studies are necessary for the identification of new prognostic biomarkers to improve care for patients with ALD, which is particularly relevant now that newborn screening for ALD is being introduced.
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Multivariate analysis and model building for classifying patients in the peroxisomal disorders X-linked adrenoleukodystrophy and Zellweger syndrome in Chinese pediatric patients
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The authors are grateful to R. Salzman (The Stop ALD Foundation) for critical review of the manuscript and helpful discussions. Work in the authors' laboratory was supported by a grant from the Netherlands Organization for Scientific Research (VENI-Grant: 016.156.033 awarded to M.E.).
The authors declare no competing financial interests.
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Kemp, S., Huffnagel, I., Linthorst, G. et al. Adrenoleukodystrophy – neuroendocrine pathogenesis and redefinition of natural history. Nat Rev Endocrinol 12, 606–615 (2016). https://doi.org/10.1038/nrendo.2016.90
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