Clinical characteristics and phenotype distribution in 10 Chinese patients with X‑linked adrenoleukodystrophy

Jia,Ming‑Rui; Wu,Wen‑Zhen; Li,Chuan‑Ming; Cai,Xiao‑Hui; Zhang,Lin; Yan,Fang; Zhu,Chan; Gu,Ming‑Hong

doi:10.3892/etm.2019.7804

Clinical characteristics and phenotype distribution in 10 Chinese patients with X‑linked adrenoleukodystrophy

Authors:
- Ming‑Rui Jia
- Wen‑Zhen Wu
- Chuan‑Ming Li
- Xiao‑Hui Cai
- Lin Zhang
- Fang Yan
- Chan Zhu
- Ming‑Hong Gu
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Affiliations: Department of Pain Management, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Emergency Internal Medicine, Shanghai Jiading Hospital of Traditional Chinese Medicine, Shanghai 201800, P.R. China, Department of Pain Management, Shanghai Jiading Hospital of Traditional Chinese Medicine, Shanghai 201800, P.R. China, Injury Department of Orthopedics, Shanghai Jiading Hospital of Traditional Chinese Medicine, Shanghai 201800, P.R. China, Department of Intensive Care Unit, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
Published online on: July 24, 2019 https://doi.org/10.3892/etm.2019.7804
Pages: 1945-1952
Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

X‑linked adrenoleukodystrophy (X‑ALD) is the most frequent type of inherited demyelinating peroxisomal disease caused by mutations in the ATP binding cassette subfamily D member 1 (ABCD1) gene. The rate of early recognition and genetic diagnosis of X‑ALD remains low due to its variable clinical manifestations. The present study summarized the clinical features Chinese X‑ALD patients and performed a follow‑up study to further precisely characterize this disease. A total of 10 patients diagnosed with X‑ALD between 1994 and 2016 at Shandong Provincial Hospital Affiliated to Shandong University (Jinan, China) were included in the present study. Through reviewing their medical records and performing telephone follow‑ups, the clinical features, biochemical laboratory data, brain images, treatments and long‑term outcomes were retrospectively summarized. Mutation analysis of the ABCD1 gene was performed in certain patients. Most of the patients (8/10) had the childhood cerebral form of X‑ALD. One patient presented with the olivo‑ponto‑cerebellar form, the rarest form of X‑ALD. In all patients, brain magnetic resonance images revealed abnormalities with typical T2‑weighted hyperintensity. Analysis of very long chain fatty acid revealed high plasma levels of hexacosanoic acid in all patients. Increased adrenocorticotropic hormone, decreased cortisol and neurophysiological manifestations were also observed. Three different mutations of the ABCD1 gene were identified in the 3 patients subjected to genotyping. During the follow‑ups, most patients took neurotrophic drugs and received hydrocortisone replacement when required. One patient received a hematopoietic stem cell transplantation, but died 1 year following the transplantation. Chronic myelopathy and peripheral neuropathy progressed with time, gradually leading to a vegetative state or paralysis within several years of clinical symptom onset. In conclusion, male patients with adrenocortical insufficiency should be further investigated for X‑ALD. Early detection is critical to prevent the progression of X‑ALD with mutation analysis of ABCD1 the most accurate method to confirm diagnosis.

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