Table_1_Broadening the Spectrum of Adulthood X-Linked Adrenoleukodystrophy: A Report of Two Atypical Cases.docx

X-linked adrenoleukodystrophy (x-ALD) is a rare genetic disorder caused by a mutation in the ABCD1 gene, which encodes for a peroxisomal very long chain fatty acid transporter. Clinically, x-ALD can present a wide spectrum of different phenotypes: asymptomatic carriers, Addison only, cerebral x-ALD, and myelopathy with/without evidence of peripheral axonopathy (Adrenomyeloneuropathy). We report on two cases of adult x-ALD, with atypical phenotypes: (Case 1) A 37-years-old male with a 2-years-long history of spastic paraparesis, urinary urgency, and subclinical adrenocortical insufficiency. As an atypical finding, the MRI showed multiple congenital brain development defects. (Case 2) A 63-years-old male with a previous diagnosis of Addison disease, with a 6-years-long history of spastic paraparesis. Two years later, he complained of severe and disabling burning pain in his feet. A nerve conduction study was normal, but a skin biopsy revealed autonomic and somatic small fiber neuropathy. In both cases, genetic testing disclosed hemizygous mutation in ABCD1 associated with x-ALD: c.1394-2A > G and p.(Thr254Met), respectively. While case 1 supports the key role of peroxisome functions in brain development, case 2 points to a possible selective and clinically relevant peripheral small fiber degeneration in x-ALD myelopathy.

X连锁肾上腺脑白质营养不良（X-linked adrenoleukodystrophy, X-ALD）是一种罕见遗传性疾病，由ABCD1基因发生突变引发，该基因编码过氧化物酶体极长链脂肪酸转运蛋白。临床上，X-ALD可呈现广泛的表型谱系：无症状携带者、单纯艾迪生病（Addison disease）、脑型X-ALD，以及伴或不伴周围轴索病证据的脊髓病（肾上腺脊髓神经病，Adrenomyeloneuropathy）。本研究报道2例成人X-ALD患者，均表现为非典型表型：（病例1）37岁男性，病程2年，出现痉挛性轻截瘫、尿急及亚临床肾上腺皮质功能不全，其头颅MRI可见多发先天性脑发育异常，此为非典型影像学表现。（病例2）63岁男性，既往确诊艾迪生病，病程6年，表现为痉挛性轻截瘫；2年后患者主诉足部出现严重且致残性灼痛。神经传导检测结果正常，但皮肤活检提示存在自主神经与躯体性小纤维神经病。两例患者的基因检测均发现与X-ALD相关的ABCD1基因半合子突变，分别为c.1394-2A>G及p.(Thr254Met)。病例1佐证了过氧化物酶体功能在脑发育中的关键作用，而病例2则提示，在X-ALD相关性脊髓病中可能存在具有临床意义的选择性周围小纤维变性。