安德森-法布里病(Anderson-Fabry Disease)同基因遗传:罕见的晚发变异病例

IF 0.5 Q4 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiogenetics Pub Date : 2024-04-07 DOI:10.3390/cardiogenetics14020006
G. Dostálová, Jaroslav Januška, Michaela Veselá, P. Reková, Anna Taborska, Martin Pleva, David Zemanek, Aleš Linhart
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引用次数: 0

摘要

安德森-法布里病(Anderson-Fabry Disease,AFD)是一种罕见的 X 连锁溶酶体贮积症,是由α-半乳糖苷酶 A 基因突变导致α-半乳糖苷酶 A 酶(α-Gal A)缺乏引起的。这种代谢缺陷会导致糖磷脂进行性积累,并使受影响器官的结构和功能受损。由于其遗传模式,男性患者为半合子,疾病表现更为严重,而女性患者大多为杂合子,由于 X 染色体失活不均匀,临床表现延迟且多变。法布里病病例通常是通过在高危人群(如终末期肾病、早发中风或原因不明的心肌病患者)中开展有针对性的筛查计划而发现的。在这里,我们描述了一个独特的病例,该病例是通过一项针对肥厚型心肌病患者的全国性筛查计划发现的同卵双生女性患者。在系统筛查之前,该患者被诊断为肥厚型梗阻性心肌病,并接受了相应的治疗,包括酒精隔消融术以降低梗阻梯度。法布里病的确诊导致在她的几个家庭成员中发现了相同的变异体。已确定的变异体为 c.644A>G,p.Asn215Ser(p.N215S),已知该变异体主要导致心脏受累,发病较晚。这种变异型适合口服小分子伴侣素米加司他治疗,该治疗开始后因患者偏头痛复发而中断,两年后再次启动。在此期间,患者接受了阿加西酶 beta 的酶替代治疗,但静脉通路情况逐渐恶化。我们的病例说明了对有肥厚型心肌病临床证据且常规诊断过程未能发现法布里病的患者进行系统筛查的重要性,尤其是具有晚发心脏表现的变异型患者。许多晚发性变异型可接受米加司他的口服活性疗法,这大大提高了治疗的舒适度。一个大型的国际 "Follow-me "登记处正在对其长期结果进行分析,该登记处旨在验证使用米加司他治疗法布里病的关键试验的有效性。
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Anderson–Fabry Disease Homozygosity: Rare Case of Late-Onset Variant
Anderson–Fabry Disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to the progressive accumulation of glycosphingolipids and the structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who, in most cases, are heterozygous with delayed and variable clinical presentation caused by uneven X-chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke, or unexplained cardiomyopathy. Here, we describe a unique case of a homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly, including with alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease led to the discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (p.N215S), which is known to cause predominant cardiac involvement with late onset of the disease. This variant is amenable to oral therapy with the small-molecule chaperone migalastat, which was started and then interrupted due to the recurrence of the patient’s migraine and then re-initiated again after two years. During this period, the patient received enzyme replacement therapy with agalsidase beta but developed progressively worsening venous access. Our case illustrates the importance of the systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom the routine diagnostic process fails to discover Fabry disease, in particular variants with late-onset cardiac manifestations. Many of the late-onset variants are amenable to orally active therapy with migalastat, which significantly improves the comfort of the treatment. Its long-term results are being analyzed by a large international “Follow-me” registry, which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.
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来源期刊
Cardiogenetics
Cardiogenetics CARDIAC & CARDIOVASCULAR SYSTEMS-
自引率
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发文量
26
审稿时长
11 weeks
期刊最新文献
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