Schiffmann R, Dwyer N K, Lubensky I A, Tsokos M, Sutliff V E, Latimer J S, Frei K P, Brady R O, Barton N W, Blanchette-Mackie E J, Goldin E
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1207-12. doi: 10.1073/pnas.95.3.1207.
Mucolipidosis type IV is an autosomal recessive lysosomal storage disease of unknown etiology that causes severe neurological and ophthalmological abnormalities. In an attempt to obtain insight into the nature of the metabolic abnormality in this disorder, we prospectively evaluated 15 consecutive patients, aged 2 to 23 years, over a period of 22 months. The finding of iron deficiency in some of the patients led us to the discovery that all patients but one had markedly elevated blood gastrin levels. None had vitamin B12 deficiency. Gastroscopy in three patients showed normal gross appearance of the mucosa in two patients, 4 and 7 years old, and mucosal atrophy in a 22-year-old. Parietal cells were present in normal numbers and contained large cytoplasmic inclusions that were confirmed immunohistochemically to be lysosomal in nature. Other gastric epithelial cells appeared normal. Parietal cells contained very few tubulovesicular membranes, suggesting cellular activation, whereas apical canaliculi appeared relatively nonactivated. Both subunits of the parietal cell H+/K+-ATPase were present, and both partially colocalized with f-actin at the apical membrane. We conclude that patients with mucolipidosis type IV are constitutively achlorhydric and have partially activated parietal cells. We hypothesize that the defective protein in this disease is closely associated with the final stages of parietal cell activation and is critical for a specific type of cellular vacuolar trafficking between the cytoplasm and the apical membrane domain.
IV型黏脂贮积症是一种常染色体隐性溶酶体贮积病，病因不明，可导致严重的神经和眼科异常。为了深入了解这种疾病代谢异常的本质，我们对15例年龄在2至23岁之间的连续患者进行了为期22个月的前瞻性评估。部分患者缺铁的发现使我们发现，除1例患者外，所有患者的血胃泌素水平均显著升高。无一例患者存在维生素B12缺乏。对3例患者进行的胃镜检查显示，2例年龄分别为4岁和7岁的患者黏膜外观正常，1例22岁患者出现黏膜萎缩。壁细胞数量正常，含有大的细胞质内含物，免疫组织化学证实其本质上为溶酶体。其他胃上皮细胞外观正常。壁细胞含有极少的微管泡膜，提示细胞活化，而顶端小管相对未活化。壁细胞H+/K+-ATP酶的两个亚基均存在，且均在顶端膜处与丝状肌动蛋白部分共定位。我们得出结论，IV型黏脂贮积症患者持续性胃酸缺乏，壁细胞部分活化。我们推测，这种疾病中存在缺陷的蛋白质与壁细胞活化的最后阶段密切相关，并且对于细胞质与顶端膜区域之间特定类型的细胞空泡运输至关重要。
