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Abstract：
BACKGROUND: Addison\'s disease and X-linked adrenoleukodystrophy (X-ALD) (Addison\'s-only) are two diseases that need to be identified. Addison\'s disease is easy to diagnose clinically when only skin and mucosal pigmentation symptoms are present. However, X-ALD (Addison\'s-only) caused by ABCD1 gene variation is ignored, thus losing the opportunity for early treatment. This study described two patients with initial clinical diagnosis of Addison\'s disease. However, they rapidly developed neurological symptoms triggered by infection. After further genetic testing, the two patients were diagnosed with X-ALD.
METHODS: We retrospectively analyzed X-ALD patients admitted to our hospital. Clinical features, laboratory test results, and imaging data were collected. Whole-exome sequencing was used in molecular genetics.
RESULTS: Two patients were included in this study. Both of them had significantly increased adrenocorticotropic hormone level and skin and mucosal pigmentation. They were initially clinically diagnosed with Addison\'s disease and received hydrocortisone treatment. However, both patients developed progressive neurological symptoms following infectious disease. Further brain magnetic resonance imaging was completed, and the results suggested demyelinating lesions. Molecular genetics suggested variations in the ABCD1 gene, which were c.109_110insGCCA (p.C39Pfs*156), c.1394-2 A > C (NM_000033), respectively. Therefore, the two patients were finally diagnosed with X-ALD, whose classification had progressed from X-ALD (Addison\'s-only) to childhood cerebral adrenoleukodystrophy (CCALD). Moreover, the infection exacerbates the demyelinating lesions and accelerates the onset of neurological symptoms. Neither the two variation sites in this study had been previously reported, which extends the ABCD1 variation spectrum.
CONCLUSIONS: Patients with only symptoms of adrenal insufficiency cannot be simply clinically diagnosed with Addison\'s disease. Being alert to the possibility of ABCD1 variation is necessary, and complete genetic testing is needed as soon as possible to identify X-ALD (Addison\'s-only) early to achieve regular monitoring of the disease and receive treatment early. In addition, infection, as a hit factor, may aggravate demyelinating lesions of CCALD. Thus, patients should be protected from external environmental factors to delay the progression of cerebral adrenoleukodystrophy.
METHODS: We retrospectively analyzed X-ALD patients admitted to our hospital. Clinical features, laboratory test results, and imaging data were collected. Whole-exome sequencing was used in molecular genetics.
RESULTS: Two patients were included in this study. Both of them had significantly increased adrenocorticotropic hormone level and skin and mucosal pigmentation. They were initially clinically diagnosed with Addison\'s disease and received hydrocortisone treatment. However, both patients developed progressive neurological symptoms following infectious disease. Further brain magnetic resonance imaging was completed, and the results suggested demyelinating lesions. Molecular genetics suggested variations in the ABCD1 gene, which were c.109_110insGCCA (p.C39Pfs*156), c.1394-2 A > C (NM_000033), respectively. Therefore, the two patients were finally diagnosed with X-ALD, whose classification had progressed from X-ALD (Addison\'s-only) to childhood cerebral adrenoleukodystrophy (CCALD). Moreover, the infection exacerbates the demyelinating lesions and accelerates the onset of neurological symptoms. Neither the two variation sites in this study had been previously reported, which extends the ABCD1 variation spectrum.
CONCLUSIONS: Patients with only symptoms of adrenal insufficiency cannot be simply clinically diagnosed with Addison\'s disease. Being alert to the possibility of ABCD1 variation is necessary, and complete genetic testing is needed as soon as possible to identify X-ALD (Addison\'s-only) early to achieve regular monitoring of the disease and receive treatment early. In addition, infection, as a hit factor, may aggravate demyelinating lesions of CCALD. Thus, patients should be protected from external environmental factors to delay the progression of cerebral adrenoleukodystrophy.
摘要：
背景：Addison病和X连锁肾上腺脑白质营养不良（X-ALD）（仅Addison病）是两种需要鉴定的疾病。当仅存在皮肤和粘膜色素沉着症状时，阿狄森氏病易于临床诊断。然而,X-ALD(Addison\'s-only)引起的ABCD1基因变异被忽略，从而失去了早期治疗的机会。这项研究描述了两名最初临床诊断为Addison病的患者。然而,他们迅速出现由感染引发的神经系统症状。经过进一步的基因检测,两名患者被诊断为X-ALD.
方法：对我院收治的X-ALD患者进行回顾性分析。临床特征,实验室测试结果，并收集影像学资料。全外显子组测序用于分子遗传学。
结果：本研究包括两名患者。两者均显着增加了促肾上腺皮质激素水平和皮肤和粘膜色素沉着。他们最初被临床诊断为患有Addison病，并接受氢化可的松治疗。然而,两名患者在感染性疾病后出现进行性神经系统症状.完成了进一步的脑部磁共振成像，结果提示有脱髓鞘病变。分子遗传学提示ABCD1基因变异，这是c.109_110insGCCA（p。C39Pfs*156),c.1394-2A>C(NM_000033)，分别。因此,这两个病人最终被诊断为X-ALD,其分类已从X-ALD（仅Addison's-only）发展为儿童期脑肾上腺脑白质营养不良（CCALD）。此外，感染加剧了脱髓鞘病变并加速了神经系统症状的发作。这项研究中的两个变异位点以前都没有报道过，扩展了ABCD1变异谱。
结论：仅有肾上腺功能不全症状的患者不能简单地在临床上诊断为Addison病。警惕ABCD1变异的可能性是必要的，并且需要尽快进行完整的基因检测，以便尽早识别X-ALD（仅Addison's-only），以实现对疾病的定期监测并尽早接受治疗。此外,感染,作为一个打击因素，可能加重CCALD的脱髓鞘病变。因此，应保护患者免受外界环境因素的影响，以延缓脑肾上腺脑白质营养不良的进展。
方法：对我院收治的X-ALD患者进行回顾性分析。临床特征,实验室测试结果，并收集影像学资料。全外显子组测序用于分子遗传学。
结果：本研究包括两名患者。两者均显着增加了促肾上腺皮质激素水平和皮肤和粘膜色素沉着。他们最初被临床诊断为患有Addison病，并接受氢化可的松治疗。然而,两名患者在感染性疾病后出现进行性神经系统症状.完成了进一步的脑部磁共振成像，结果提示有脱髓鞘病变。分子遗传学提示ABCD1基因变异，这是c.109_110insGCCA（p。C39Pfs*156),c.1394-2A>C(NM_000033)，分别。因此,这两个病人最终被诊断为X-ALD,其分类已从X-ALD（仅Addison's-only）发展为儿童期脑肾上腺脑白质营养不良（CCALD）。此外，感染加剧了脱髓鞘病变并加速了神经系统症状的发作。这项研究中的两个变异位点以前都没有报道过，扩展了ABCD1变异谱。
结论：仅有肾上腺功能不全症状的患者不能简单地在临床上诊断为Addison病。警惕ABCD1变异的可能性是必要的，并且需要尽快进行完整的基因检测，以便尽早识别X-ALD（仅Addison's-only），以实现对疾病的定期监测并尽早接受治疗。此外,感染,作为一个打击因素，可能加重CCALD的脱髓鞘病变。因此，应保护患者免受外界环境因素的影响，以延缓脑肾上腺脑白质营养不良的进展。
