[1] Clinically, most affected individuals display developmental delay, lack of tears, elevated liver transaminases and a movement disorder.

Without N-glycanase, N-glycosylated proteins that are misfolded in the endoplasmic reticulum cannot be degraded, and thus accumulate in the cytoplasm of cells.

[3][4] Four common findings have been identified in a majority of patients: developmental delay or intellectual disability of varying degrees, lack of or greatly reduced tears, elevated liver transaminases, and a complex movement disorder.

[2] NGLY1 deficiency can be suspected based on clinical findings, however confirmation of the diagnosis requires the identification of biallelic pathogenic variants in NGLY1 through genetic testing.

Currently, the majority of individuals reported with NGLY1 deficiency are of northern European descent, however this likely reflects an ascertainment bias in these early stages of the disorder.

[1] NGLY1 deficiency has received a large amount of attention, despite its rarity, due to the children of two media-savvy families being afflicted.