Ngly1 is a genetic disorder of the endoplasmic reticulum-associated degradation pathway caused by a deficiency of a cytosolic enzyme N-glycanase 1 (encoded by the gene Ngly1), which is required for cleaving N-linked glycans from misfolded glycoproteins prior to degradation. Lacking N-glycanase leaves the body with an impaired capacity to degrade misfolded glycoproteins, which accumulate in the cells of patients.
Ngly1-deficient patients have a striking clinical triad consisting of abnormal tear production, choreoathetosis, liver disease, global developmental delay, acquired microcephaly, hypotonia, EEG abnormalities with or without overt seizures, brain imaging abnormalities, peripheral neuropathy, and constipation.
To date, 30 patients were diagnosed with Ngly1 deficiency. Efforts are ongoing to identify many more who may have been misdiagnosed with diseases of similar physical characteristics.
There are currently no FDA approved treatments specific to Ngly1 deficiency. Supportive care is aimed at treating symptoms and sequelae.
Together with the Grace Wilsey Foundation, Glycomine is working on the development of Ngly1 enzyme replacement therapy intended to replace the deficient enzyme to restore the process of misfolded glycoprotein degradation.