Lysosomal alpha-N-acetylgalactosaminidase deficiency, the enzymatic defect in angiokeratoma corporis diffusum with glycopeptiduria.
Lysosomal alpha-N-acetylgalactosaminidase deficiency, the enzymatic defect in angiokeratoma corporis diffusum with glycopeptiduria.
复制标题
溶酶体α-N-乙酰半乳糖胺酶缺乏症，弥漫性体质血管角化瘤伴糖肽尿的酶缺陷。
DOI：
10.1172/jci115357
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Desnick,RJ
中科院分区：
文献类型：
--
作者：
Kanzaki,T;Wang,AM;Desnick,RJ
最近，我们报道了一例46岁的日本女性的血管角化瘤伴糖氨基酸尿。通过酶分析消除了皮肤表现的已知原因，进一步表征尿中积累的o型唾液肽，揭示了由于溶酶体α - n -乙酰半乳糖胺酶缺乏症导致的婴儿神经轴突营养不良患者排泄的唾液肽的特性。先证患者的α - n -乙酰半乳糖胺酶活性和蛋白质的调查显示，其活性低于正常的2%，且缺乏可检测到的免疫反应酶蛋白，其结果与婴儿神经轴突营养不良和α - n -乙酰半乳糖胺酶缺乏症的患者相似。此外，先证未受影响的后代α -n -乙酰半乳糖胺酶活性为正常水平的一半，这与酶缺乏是常染色体隐性性状的主要代谢缺陷相一致。成人先证者皮肤和血细胞的超微结构检查显示存在明显的溶酶体内含物，内含弥漫性无定形和丝状物质。相反，这些形态学上的发现在婴儿神经轴突营养不良和α - n -乙酰半乳糖胺酶缺乏症患者的非神经组织中没有观察到。这些研究记录了两种形式的α - n -乙酰半乳糖胺酶缺乏症和唾液肽血症的发生，一种是严重的婴儿发病形式的神经轴突营养不良，没有血管角化瘤或内脏溶酶体包涵体，另一种是成人发病形式，其特征是血管角化瘤，广泛的唾液糖肽溶酶体积聚，没有可检测到的神经系统受累。图片
Recently a novel case of angiokeratoma corporis diffusum with glycoaminoaciduria was described in a 46-yr-old Japanese woman. Known causes of the cutaneous manifestation were eliminated by enzyme analyses, and further characterization of the accumulated urinary O-linked sialopeptides revealed identity to those excreted by patients with an infantile neuroaxonal dystrophy due to lysosomal alpha-N-acetylgalactosaminidase deficiency. Investigation of the alpha-N-acetylgalactosaminidase activity and protein in the proband revealed less than 2% of normal activity and the absence of detectable immunoreactive enzyme protein, findings comparable to those in the patients with infantile neuroaxonal dystrophy and alpha-N-acetylgalactosaminidase deficiency. In addition, the proband's unaffected offspring had half-normal levels of alpha-N-acetylgalactosaminidase activity, consistent with this enzymatic deficiency being the primary metabolic defect in this autosomal recessive trait. Ultrastructural examination of skin and blood cells from the adult proband revealed the presence of prominent lysosomal inclusions containing diffuse amorphous and filamentous material. In contrast, these morphologic findings were not observed in the nonneural tissues from patients with infantile neuroaxonal dystrophy and alpha-N-acetylgalactosaminidase deficiency. These studies document the occurrence of two forms of alpha-N-acetylgalactosaminidase deficiency and sialopeptiduria, a severe infantile-onset form of neuroaxonal dystrophy without angiokeratoma or visceral lysosomal inclusions and an adult-onset form characterized by angiokeratoma, extensive lysosomal accumulation of sialoglycopeptides and the absence of detectable neurologic involvement.Images