Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review.
Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review.
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DOI：
10.1111/neup.12230
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Dickson DW
中科院分区：
文献类型：
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作者：
Ogaki K;Koga S;Aoki N;Lin W;Suzuki K;Ross OA;Dickson DW
x -连锁肾上腺脑白质营养不良（X-ALD）是最常见的过氧化物酶体疾病，由ABCD1突变引起。一种主要涉及小脑和脑干的小脑-脑干显性形式在文献综述中进行了总结，尸检证实的病例非常罕见。我们报告一位69岁的白人男性，他被诊断出患有这种罕见的疾病，并描述了神经病理、超微结构和遗传分析。他没有肾上腺功能不全，也没有X-ALD或Addison病的家族史。他最初的症状是34岁时暂时失明。其主要症状为慢性进行性步态障碍、下肢无力、痉挛、自主神经衰竭和小脑共济失调，提示可能存在多系统萎缩（MSA）。他还患有癫痫、听力丧失和感觉障碍。脑MRI未见明显萎缩，脑、脑干、小脑未见明显白质病变。他死于多系统萎缩，享年69岁。镜下分析显示轻度斑片状髓磷脂稀疏，血管周围以小脑和枕叶为主的pas阳性、cd68阳性巨噬细胞簇，但也累及视束和内囊。小脑白质电镜显示，X-ALD典型的巨噬细胞中有裂隙样的三层细胞质内含物，这促使基因分析揭示了一种新的ABCD1突变，p.R163G。鉴于病理表现相对温和，病程较长，观察到的病理可能是缓慢而惰性的疾病过程的结果。我们描述了一位散发性小脑-脑干显性形式的X-ALD患者，临床病程长，病理表现轻微，ABCD1 p.R163G替代。我们也回顾了34例成人发病的小脑-脑干显性形式的X-ALD。虽然罕见，但在MSA的鉴别诊断中应考虑X-ALD。
X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy confirmed cases exceedingly rare. We report a 69-year-old white man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison’s disease. His initial symptom was temporary loss of eyesight at age 34 years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities, and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss, and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69 years with a diagnosis of multiple system atrophy. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be considered in the differential diagnosis of MSA.