Department of Cardiology, Vaasa Central Hospital, Vaasa, Finland.
Department of Pulmonology, Vaasa Central Hospital, Vaasa, Finland.
Mol Genet Genomic Med. 2022 May;10(5):e1915. doi: 10.1002/mgg3.1915. Epub 2022 Mar 4.
Fabry disease (FD) is caused by a defect in α-galactosidase A gene (GLA) which leads to a progressive accumulation of neutral shingolipids, mainly globotriaosylceramide and its metabolites in several organs. Pulmonary manifestations of FD mimic chronic obstructive pulmonary disease and are disproportionate to smoking status. The effect of enzyme replacement therapy (ERT) on pulmonary function is inconclusive. We studied the effect of ERT on pulmonary function in FD with a mutation p. Arg227Ter (p.R227*) which is one of the most common mutations causing classical FD in Finland and worldwide.
Patients were annually examined by multidisciplinary team. Based on the maximal pulmonary oxygen consumption at the baseline, either cardiopulmonary exercise test or combination of spirometry and 6-minute walking test were performed annually during 5-year follow-up.
Four males and eight females met the criteria for ERT and were included in this study. Three of 12 patients had obstruction by GOLD criterion before ERT, and one had a borderline obstruction. In 5 years, five patients were classified as obstructive, although the real change in FEV1/FVC was unchanged in the whole cohort. Only one patient was an active smoker.
In nonsmokers, pulmonary manifestations in classical FD are mild and might be stabilized by ERT.
法布里病（FD）是由α-半乳糖苷酶 A 基因（GLA）缺陷引起的，导致中性鞘糖脂，主要是神经节苷脂和其代谢物在多个器官中进行性积累。FD 的肺部表现类似于慢性阻塞性肺疾病，与吸烟状况不成比例。酶替代疗法（ERT）对肺功能的影响尚无定论。我们研究了ERT 对芬兰和全球最常见的经典 FD 致病突变 p.Arg227Ter（p.R227*）的 FD 患者肺功能的影响。
患者每年由多学科团队进行检查。根据基线时最大肺氧耗量，在 5 年随访期间，每年进行心肺运动试验或肺量计和 6 分钟步行试验的组合。
符合 ERT 标准的 4 名男性和 8 名女性符合纳入本研究的条件。在 ERT 之前，12 名患者中有 3 名符合 GOLD 标准的阻塞性肺病，1 名有阻塞性肺病边缘。在 5 年内，有 5 名患者被归类为阻塞性肺病，尽管整个队列的 FEV1/FVC 实际变化没有改变。只有 1 名患者是主动吸烟者。
在不吸烟的人群中，经典 FD 的肺部表现较轻，ERT 可能使其稳定。
