Acid Sphingomyelinase Deficiency (ASMD), or Niemann-Pick type A/B disease, is a rare lipid storage disorder leading to accumulation of sphingomyelin and its precursors primarily in macrophages. The disease has a broad phenotypic spectrum ranging from a fatal infantile form with severe neurological involvement (the infantile neurovisceral type) to a primarily visceral form with different degrees of pulmonary, liver, spleen and skeletal involvement (the chronic visceral type). With the upcoming possibility of treatment with enzyme replacement therapy, the need for biomarkers that predict or reflect disease progression has increased. Biomarkers should be validated for their use as surrogate markers of clinically relevant endpoints. In this review, clinically important endpoints as well as biochemical and imaging markers of ASMD are discussed and potential new biomarkers are identified. We suggest as the most promising biomarkers that may function as surrogate endpoints in the future: diffusion capacity measured by spirometry, spleen volume, platelet count, low-density lipoprotein cholesterol, liver fibrosis measured with a fibroscan, lysosphingomyelin and walked distance in six minutes. Currently, no biomarkers have been validated. Several plasma markers of lipid-laden cells, fibrosis or inflammation are of high potential as biomarkers and deserve further study. Based upon current guidelines for biomarkers, recommendations for the validation process are provided.

中文翻译：

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酸性鞘磷脂酶缺乏症的生化和成像参数：作为生物标记物的潜在用途。

酸性鞘磷脂酶缺乏症（ASMD）或Niemann-Pick A / B型疾病是一种罕见的脂质储存障碍，导致鞘磷脂及其前体主要在巨噬细胞中蓄积。该疾病具有广泛的表型谱，范围从致命的婴儿形式到严重的神经系统受累（婴儿神经内脏型）到具有不同程度的肺，肝，脾和骨骼受累的主要内脏型（慢性内脏型）。随着即将出现的用酶替代疗法治疗的可能性，对预测或反映疾病进展的生物标志物的需求增加了。应验证生物标志物是否可用作临床相关终点的替代标志物。在这篇评论中 讨论了ASMD的临床重要终点以及生化和成像标记，并确定了潜在的新生物标记。我们建议作为将来可能成为替代终点的最有希望的生物标志物：通过肺活量测定法测定的扩散能力，脾脏体积，血小板计数，低密度脂蛋白胆固醇，通过纤维扫描测定的肝纤维化，溶血鞘磷脂和六分钟的步行距离。目前，尚未验证生物标记。脂质负载细胞，纤维化或炎症的几种血浆标志物作为生物标志物具有很高的潜力，值得进一步研究。根据当前的生物标志物指南，提供了验证过程的建议。我们建议作为将来可能成为替代终点的最有希望的生物标志物：通过肺活量测定法测定的扩散能力，脾脏体积，血小板计数，低密度脂蛋白胆固醇，通过纤维扫描测定的肝纤维化，溶血鞘磷脂和六分钟的步行距离。目前，尚未验证生物标记。脂质负载细胞，纤维化或炎症的几种血浆标志物作为生物标志物具有很高的潜力，值得进一步研究。根据当前的生物标志物指南，提供了验证过程的建议。我们建议作为将来可能成为替代终点的最有希望的生物标志物：通过肺活量测定法测定的扩散能力，脾脏体积，血小板计数，低密度脂蛋白胆固醇，通过纤维扫描测定的肝纤维化，溶血鞘磷脂和六分钟的步行距离。目前，尚未验证生物标记。脂质负载细胞，纤维化或炎症的几种血浆标志物作为生物标志物具有很高的潜力，值得进一步研究。根据当前的生物标志物指南，提供了验证过程的建议。脂质负载细胞，纤维化或炎症的几种血浆标志物作为生物标志物具有很高的潜力，值得进一步研究。根据当前的生物标志物指南，提供了验证过程的建议。脂质负载细胞，纤维化或炎症的几种血浆标志物作为生物标志物具有很高的潜力，值得进一步研究。根据当前的生物标志物指南，提供了有关验证过程的建议。