Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Am J Med Genet A. 2022 Jul;188(7):2005-2018. doi: 10.1002/ajmg.a.62737. Epub 2022 Mar 26.
Leukocyte adhesion deficiency type II (LAD II, also known as SLC35C1-congenital disorder of glycosylation) is an autosomal recessive disorder characterized by growth and cognitive impairment, peripheral neutrophilia, recurrent infections, and the Bombay blood phenotype. A subset of patients with a milder presentation has been described with short stature and developmental delay but minimal immune and hematologic features. Some patients with LAD II benefit from oral fucose therapy, though this has not been previously studied in patients with milder disease. In this study, we describe two new patients from separate families with the milder variant of LAD II and review the published literature on this rare disorder. We demonstrate improvement in speech and cognition, CD15 expression, and core fucosylation of serum glycoproteins after 27 months of oral fucose supplementation in one patient. These patients further support the stratification of this disorder into distinct subtypes, a classical severe and an attenuated variant, and provide preliminary evidence of benefit of fucose therapy in the latter group.
白细胞黏附缺陷 II 型(LAD II,也称为 SLC35C1-先天性糖基化障碍)是一种常染色体隐性遗传疾病,其特征为生长和认知障碍、外周中性粒细胞增多、反复感染和 Bombay 血型表型。已描述了一组具有较轻表现的患者,其特征为身材矮小和发育迟缓,但免疫和血液学特征最小。一些 LAD II 患者受益于口服岩藻糖治疗,尽管此前尚未在病情较轻的患者中对此进行研究。在这项研究中,我们描述了来自两个不同家庭的两个新患者,他们患有较轻的 LAD II 变异型,并回顾了该罕见疾病的已发表文献。我们证明了在一名患者中接受 27 个月的口服岩藻糖补充后,言语和认知能力、CD15 表达以及血清糖蛋白的核心岩藻糖基化得到改善。这些患者进一步支持将该疾病分为不同亚型,即经典的严重型和减轻型,并且为后者组中岩藻糖治疗的益处提供了初步证据。