About

NGLY1 deficiency (or N-glycanase deficiency) is an extremely rare genetic disorder.  It falls within the family of Congenital Disorders of Glycosylation (CDG).

In this disorder, the cells of the body cannot synthesize the enzyme N-glycanase.

N-glycanase 1 (encoded by the gene NGLY1) is responsible for cleaving N-linked glycans from misfolded glycoproteins, so that the body can recycle them.

Lacking N-glycanase leaves the body with an impaired capacity to recycle misfolded glycoproteins, which appear to accumulate in the cells of patients and which may cause harm.

N-glycanase deficiency is recessive: when parents are carriers, they have a 25% chance of producing a child with the disorder for each pregnancy.

What are the symptoms / features?

• Global developmental delay
• Movement disorder
• A lack of tears (alacrima or hypolacrima): While patients have some moisture in their eyes, they have difficulty producing tear drops when crying.
• Liver dysfunction: Patients present with elevated liver transaminases such as AST, ALT and sometimes AFP. Liver values may trend toward the normal range over time.
• A smaller head (microcephaly): Patients tend to have a smaller head circumference, this may be relative to body size and/or acquired over time.
• Diminished reflexes: Some patients do not respond at all or barely respond to reflex tests.
• (As-yet) unidentified material stored in liver cells: There appears to be something stored in the cytoplasm of liver cells.
• Seizures: About half of all patients have observable seizures, but many of them are not recognizable to non-experts as seizures. Common seizure types include sudden jerks or startles (myoclonic), drops (atonic) and staring spells (absence). Patient EEGs are often described as "abnormal."
• Hypotonia
• Peripheral neuropathy

The Grace Wilsey Foundation has created a video explaining NGLY1:

 

What is NGLY1.org?

NGLY1.org is a patient-run, non-profit organization registered as the NGLY1 Foundation with the mission to eliminate the challenges of N-glycanase deficiency through research, awareness, and support.  NGLY1.org has the following goals:

1. to fund and conduct the science to understand, treat and cure NGLY1 deficiency;
2. to educate clinicians, researchers, decision-makers, and the public on NGLY1 deficiency; and
3. to identify NGLY1 patients and foster a supportive community.