Cainelli Francesca, Argandykov Dias, Kaldarbekov Dauren, Mukarov Murat, Tran Thi Phuong Liên, Germain Dominique P
Raffles Medical Group Clinic, Phnom Penh, Cambodia.
Faculty of Medicine, University of Puthisastra, Phnom Penh, Cambodia.
Front Genet. 2021 Apr 27;12:657824. doi: 10.3389/fgene.2021.657824. eCollection 2021.
Fabry disease (FD, OMIM #301500) is a rare, progressive, X-linked inherited, genetic disease due to the functional deficiency of lysosomal α-galactosidase (α-GAL) that leads to the accumulation of glycosphingolipids (mainly globotriaosylceramide or Gb) and its derivative globotriaosylsphingosine or lyso-Gb. Classic FD is a multisystem disorder which initially presents in childhood with neuropathic pain and dermatological, gastrointestinal, ocular, and cochleo-vestibular manifestations. Over time, end-organ damage such as renal failure, cardiac arrhythmia and early stroke may develop leading to reduced life expectancy in the absence of specific treatment. We describe two Kazakh patients who presented in adulthood with a delayed diagnosis. We conducted also a family screening through cascade genotyping. This is the first description of cases of Fabry disease in Central Asia. An extensive family pedigree enabled the identification of ten additional family members. Patients with rare genetic diseases often experience substantial delays in diagnosis due to their rarity and non-specific symptoms, which can negatively impact their management and delay treatment. FD may be difficult to diagnose because of the non-specificity of its early and later-onset symptoms and its X-linked inheritance. Raising awareness of clinicians is important for earlier diagnosis and optimal outcome of specific therapies.
法布里病（FD，OMIM #301500）是一种罕见的、进行性的、X连锁遗传性疾病，由于溶酶体α-半乳糖苷酶（α-GAL）功能缺陷，导致糖鞘脂（主要是三己糖神经酰胺或Gb）及其衍生物三己糖神经鞘氨醇或溶酶体-Gb蓄积。典型的FD是一种多系统疾病，最初在儿童期表现为神经性疼痛以及皮肤、胃肠道、眼部和耳蜗-前庭症状。随着时间的推移，可能会出现终末器官损害，如肾衰竭、心律失常和早期中风，在没有特异性治疗的情况下会导致预期寿命缩短。我们描述了两名成年后才被延迟诊断的哈萨克族患者。我们还通过级联基因分型进行了家族筛查。这是中亚地区法布里病病例的首次描述。一个广泛的家族谱系使我们能够识别出另外10名家庭成员。患有罕见遗传病的患者往往由于疾病罕见和症状不特异而在诊断上出现显著延迟，这可能会对他们的治疗管理产生负面影响并延误治疗。由于FD早期和晚期症状的非特异性以及X连锁遗传，其可能难以诊断。提高临床医生的认识对于早期诊断和特定疗法的最佳疗效至关重要。
