Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
Pediatric Endocrinology and Metabolism Department, Mofid Children Hospital, Shahid Beheshti, University of Medical Science, Tehran, Iran.
Eur J Med Genet. 2021 Mar;64(3):104146. doi: 10.1016/j.ejmg.2021.104146. Epub 2021 Jan 23.
NGLY1 deficiency is a recently described autosomal recessive disorder, involved in deglycosylation of proteins, and for that reason grouped as the congenital disorders of deglycosylation together with the lysosomal storage disorders. The typical phenotype is characterized by intellectual disability, liver malfunctioning, muscular hypotonia, involuntary movements, and decreased or absent tear production. Liver biopsy demonstrates vacuolar amorphous cytoplasmic storage material. NGLY1 deficiency is caused by bi-allelic variants in NGLY1 which catalyzes protein deglycosylation. We describe five patients from two families with NGLY1 deficiency due to homozygosity for two novel NGLY1 variants, and compare their findings to those of earlier reported patients. The typical features of the disorder are present in a limited way, and there is intra-familial variability. In addition in one of the families the muscle atrophy and posture abnormalities are marked. These can be explained either as variability of the phenotype or as sign of slowly progression of features as the present affected individuals are older than earlier reported patients.
NGLY1 缺乏症是一种新近描述的常染色体隐性疾病，涉及蛋白质的去糖基化，因此与溶酶体贮积症一起被归类为先天性糖基化缺陷。典型表型的特征为智力残疾、肝功能异常、肌肉张力减退、不自主运动以及泪液产生减少或缺失。肝活检显示空泡状无定形细胞质贮存物质。NGLY1 缺乏症是由 NGLY1 的双等位基因突变引起的，该基因催化蛋白质去糖基化。我们描述了来自两个家系的五名 NGLY1 缺乏症患者，他们均为两个新的 NGLY1 变异的纯合子，并将其发现与先前报道的患者进行了比较。该疾病的典型特征表现有限，存在家族内变异性。此外，在其中一个家系中，肌肉萎缩和姿势异常较为明显。这些既可以解释为表型的变异性，也可以解释为随着目前受影响的个体年龄大于先前报道的患者，特征进展缓慢的迹象。
