What is NGLY1 Deficiency?
NGLY1 Deficiency is an ultra rare genetic disorder caused by mutations in the NGLY1 gene. This disease causes issues in multiple body systems, which range from neurological impairments to issues with motor function . As of April 2025, there have only been 150 confirmed cases of NGLY1 Deficiency around the world.
Grace Science Foundation is working to fund research and find a cure for NGLY1 Deficiency and connect patient families to the NGLY1 Family Community.
NGLY1 Gene
Genes are like individual instruction manuals for proteins and components in cells that make up our bodies, directing our cells how to work. Humans have over 20,000 known genes with important roles that range from telling your cells how to digest food and grow into muscle tissue, to sending chemical signals in your brain. When a gene is mutated, this causes written errors in the instruction manual and can prevent cells from operating correctly.
The NGLY1 gene provides instructions for making a protein called NGLY1 (short for N-glycanase 1), which plays an important role in breaking down sugar-proteins in our cells for their removal – like taking out garbage in a cell. When NGLY1 doesn’t function properly, this can lead to the accumulation of cellular waste and cause serious problems.
NGLY1 Deficiency
NGLY1 Deficiency (also called congenital disorder of glycosylation; CDDG) is an ultra-rare genetic disorder caused by mutations in the NGLY1 gene. It is an autosomal recessive disorder, which means a child must inherit two mutated NGLY1 genes (one from each parent) to have NGLY1 Deficiency. Parents that are carriers have one normal and one mutated NGLY1 gene and do not have the disease or show symptoms of the disease.
When someone has NGLY1 Deficiency, their body is unable to make enough of the NGLY1 protein properly and cellular waste is not properly degraded. This causes a buildup of improperly processed proteins in the body, which can affect different organs and systems, leading to a range of symptoms and shortened life expectancy.
Core symptoms include:
- Global developmental delay
- Intellectual disability
- Hypotonia ("floppy body")
- Hypo(alacrima) ("lack of tears")
- Hyperkinetic ("jerky") movements
Other symptoms may include:
- Absent speech
- Seizures
- Liver Issues
- Ataxia (uncoordinated movement)
- Brain wave abnormalities
- Microcephaly (small head)
- Tremors
- Eye Issues
- Chronic constipation
- Sleeping difficulties
- And more...
Diagnosis
The first diagnosed case of NGLY1 Deficiency was in 2012. Since then, the Grace Science Foundation has identified over 120 patients diagnosed with NGLY1 Deficiency from around the world. Like most rare-diseases, the journey to an accurate diagnosis can be long. The average time it takes to receive an NGLY1 Deficiency diagnosis is 6 years. Many patients are undiagnosed or misdiagnosed for years due to its rarity and broad range of symptoms.
A diagnosis of NGLY1 Deficiency can be made through genetic testing that confirms two mutated copies of the NGLY1 gene. Common genetic tests include whole exome sequencing (WES), whole genome sequencing (WGS), or a sequencing panel that includes NGLY1. Ask your doctor for an NGLY1 genetic test if you believe your child may have NGLY1 Deficiency.
If a genetic test cannot determine a diagnosis, a test for the NGLY1 Deficiency biomarker GNA can be used to support a diagnosis. The Grace Science Foundation can help facilitate this test to confirm a diagnosis. Contact our email info@gracescience.org for more information.
HOPE FOR A CURE
There is work being done to find a cure. Hundreds of researchers, scientistics, and patients are coming together to push the needle forward on NGLY1 research and develop potential therapeutics. This is the mission of the Grace Science Foundation. We are working non-stop to advance scientific and medical knowledge of NGLY1 Deficiency. By working to find a cure, we hope to gain knowledge that can help treat countless other diseases.
We thank all of our patient families that have devoted time and energy to advancing knowledge of NGLY1 Deficiency. It is your dedication to your children and the NGLY1 Deficiency patient community that makes finding a cure possible.
Interested in participation in NGLY1 clinical trials?
List of current clinical trials (currently enrolling):
Patient Resources
- Download our NGLY1 Deficiency Handbook (2023)
- Download our NGLY1 Patient Flyer (2023)
- Download our NGLY1 Clinician Flyer (2023)
- Download our GNA Biomarker Handout (2024)
NGLY1 Research Papers
- Ocular Features of NGLY1 Deficiency (Levy 2023)
- NGLY1 Deficiency: a Prospective Natural History Study (Tong 2023)
- AAV9-NGLY1 Gene Therapy in NGLY1 Deficiency Rat Model (Zhu, 2022)
- GNA is a Biomarker for NGLY1 Deficiency (Mueller 2022)
- Delineating the Epilepsy Phenotype of NGLY1 Deficiency (Levy 2022)
- NGLY1 Deficiency: Incidence, Features, & Genotypic spectrum (Stanclift, 2022)
- Orthopedic Phenotyping of NGLY1 Deficiency (Cahan 2019)
- Prospective Phenotyping of NGLY1 Deficiency (Lam 2017)
- Additional NGLY1 Research Papers