Diverse clinical manifestations of X-linked adrenoleukodystrophy in a Chinese family with identical multisite variants of ABCD1 gene

Zhang, Lin; Zhao, Sijia; Wang, Zhi Hong

doi:10.1097/ypg.0000000000000292

Cited by 1 publication

(1 citation statement)

References 26 publications

(49 reference statements)

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“…Most cases occurred in newborns and adolescents and appeared as cerebral ALD (CALD) phenotype (17,18). Though this mutation is comparatively rarely reported in patients with late-onset spastic paraplegia as the first symptom, our results are consistent with the existing reports on AMN (19,20). Patient 2 with c.160_170delACGCAGGAGGC suffered from behavioral and personality changes, visual impairment, and auditory processing problems within a short course of clinical onset, except for rapidly progressive spinal cord symptoms.…”

Section: Discussionsupporting

confidence: 92%

Novel mutations in the ABCD1 gene caused adrenomyeloneuropathy in the Chinese population

Zhang²,

Huang³

et al. 2023

Front. Neurol.

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BackgroundAs a rare genetic disease, adrenomyeloneuropathy (AMN) is the most common adult phenotype of X-linked adrenoleukodystrophy (X-ALD). Mutations in the ABCD1 gene have been identified to cause AMN.MethodsWe applied clinical evaluation, laboratory tests, and neuroimaging on three patients with progressive spastic paraparesis. In genetic analysis, we investigated ABCD1 gene mutations by whole-exome sequencing and Sanger sequencing. Bioinformatics tools were used to predict the effects of identified ABCD1 mutations on the protein.ResultsAll three patients were men with adult-onset disease, mainly characterized by progressive spastic paraparesis. Among them, two patients had peripheral neuropathy and one patient had signs of adrenal insufficiency. All three patients showed cerebral involvement on brain MRI, while two patients were found with diffuse cord atrophy on spinal MRI. High-VLCFA levels in plasma, as well as C24:0/C22:0 and C26:0/C22:0 ratios, were found in all three patients. In addition, three different ABCD1 mutations were identified in three unrelated Chinese families, including one known mutation (c.1415_1416delAG) and two novel mutations (c.217C>T and c.160_170delACGCAGGAGGC). Based on the clinical assessment, radiographic, biochemical, and genetic testing, the final diagnosis was AMN in these patients with spastic paraparesis.ConclusionThis study reported three patients with AMN and identified two novel mutations in the ABCD1 in the Chinese population. Our finding emphasized that X-ALD is an important cause of adult-onset spastic paraplegia. Thus, neuroimaging, VLCFA testing, and especially the detection of the ABCD1 gene have important implications for the etiological diagnosis of adult patients with spastic paraplegia.

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Section: Discussionsupporting

confidence: 92%