成人慢性内脏酸性鞘磷脂酶缺乏症的自然病程:制定治疗标准的第一步。

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Inherited Metabolic Disease Pub Date : 2024-08-23 DOI:10.1002/jimd.12789
Eline C B Eskes, Laura van Dussen, Marion M M G Brands, Frédéric M Vaz, Johannes M F G Aerts, André B P van Kuilenburg, Barbara Sjouke, Carla E M Hollak
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引用次数: 0

摘要

酸性鞘磷脂酶缺乏症(ASMD)是一种超罕见的溶酶体贮积病,其表现范围很广,既有严重的神经病变,也有轻微的慢性内脏病变。慢性内脏亚型的表现多种多样,包括不同程度的肝脾肿大、肺部疾病和血脂异常。本研究旨在深入了解慢性内脏型成人患者的自然病程。在此基础上,我们提出了酶替代疗法(ERT)启动和随访的暂定标准。我们在一项前瞻性研究中收集了 23 名成年患者的数据。我们收集了临床、遗传和人口统计学数据、血浆测量、腹部成像、肺部成像、肺功能测试和生活质量问卷。根据几种临床、生化和放射学指标(即脾脏体积、血小板水平、肝脏体积、丙氨酸氨基转移酶[ALT]水平、肺部对一氧化碳的弥散能力[DLCO]、壳三糖苷酶活性和溶血磷脂酰肌球蛋白[LSM])评估疾病的稳定性。心血管风险根据性别、年龄、吸烟、收缩压和血脂状况进行估算。生活质量通过 36 项简表健康调查和健康评估问卷进行评估。中位随访时间为 6.1 年(1.3-19.5 年不等)。最常见的表现为脾肿大(100%)、高密度脂蛋白胆固醇(HDL-C)血浆水平下降(83%)、瞬时弹性成像测量的脂肪变性(82%)、血小板减少(64%)、肝肿大(52%)和弥散能力下降(45%)。大多数指标在随访期间保持稳定。有 12 名患者的病情出现进展:脾脏体积 4 例,肝脏体积 2 例,DLCO 3 例,壳三糖苷酶活性 7 例,LSM 3 例。一名患者的四项指标均显示病情恶化,但该患者在最后一次就诊时并未报告任何问题。对心血管风险进行了估算,发现半数 40 岁以上的患者心血管风险增加。患者报告的生活质量与普通人群没有差异,但观察到严重肺部受累患者和无肺部受累患者的 36 项简表健康调查(SF-36)中位数得分存在差异。此外,还提出了开始治疗和治疗效果的暂定标准。总之,慢性内脏亚型 ASMD 患者的病程以稳定为主。我们建议,只有在疾病进展或出现症状时,才应根据个体情况启动 ERT。有必要收集和分析现实世界的数据,以完善未来的开始、停止和随访标准。
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Natural disease course of chronic visceral acid sphingomyelinase deficiency in adults: A first step toward treatment criteria.

Acid sphingomyelinase deficiency (ASMD) is an ultra-rare lysosomal storage disease with a broad spectrum of manifestations ranging from severe neuropathic forms to attenuated, chronic visceral forms. Manifestations of the chronic visceral subtype are variable and encompass different degrees of hepatosplenomegaly, pulmonary disease and dyslipidemia. The aim of this study was to provide insights into the natural course of adult patients with the chronic visceral subtype. Based on these insights, we proposed tentative criteria for initiation and follow-up of enzyme replacement therapy (ERT). The data of 23 adult patients were collected in a prospective study. Clinical, genetic and demographic data, plasma measurements, abdominal imaging, pulmonary imaging, pulmonary function tests and quality of life questionnaires were collected. Stability of disease based on several clinical, biochemical and radiological markers (i.e., spleen volume, platelet levels, liver volume, alanine aminotransferase [ALT] levels, diffusion capacity of the lungs for carbon monoxide [DLCO] chitotriosidase activity and lysosphingomyelin [LSM]) was assessed. Cardiovascular risk was estimated based on sex, age, smoking, systolic blood pressure and lipid profile. Quality of life was evaluated with the 36-Item Short Form Health Survey and the Health Assessment Questionnaire. Median follow-up was 6.1 years (range 1.3-19.5 years). The most common manifestations were splenomegaly (100%), decreased high-density lipoprotein cholesterol (HDL-C) plasma levels (83%), (signs of) steatosis measured with transient elastography (82%), thrombocytopenia (64%), hepatomegaly (52%) and decreased diffusion capacity (45%). The majority of markers remained stable during follow-up. Twelve patients showed progression of disease: four for spleen volume, two for liver volume, three for DLCO, seven for chitotriosidase activity and three for LSM. One patient showed progression of disease based on four markers, although this patient did not report any problems at the last visit. Cardiovascular risk was estimated and was increased in half of the patients older than 40 years. Patient-reported quality of life did not differ from the general population, but differences in median 36-Item Short Form Health Survey (SF-36) scores of patients with severe pulmonary involvement and those of patients without pulmonary involvement were observed. Tentative criteria for initiation and effect of therapy were proposed. In conclusion, the chronic visceral subtype of ASMD showed a predominantly stable disease course in this cohort. We propose that ERT should be initiated on an individual basis and only in case of progression or symptomatic disease. Collection and analysis of real world data are necessary to refine start, stop and follow-up criteria in the future.

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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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