What are the other Names for this Condition? (Also known as/Synonyms)

• Congenital Disorder of Deglycosylation (CDDG)
• Congenital Disorder of Glycosylation Type IV (CDGIV)
• NGLY1 Deficiency Disorder

What is Deficiency of N-Glycanase 1? (Definition/Background Information)

• Deficiency of N-Glycanase 1 (NGLY1 Deficiency) Disorder is a complex neurological syndrome in which there is a deficiency of an enzyme   known as N-glycanase 1 (NGLY1). This enzyme normally helps the body remove proteins that are not functioning properly
• The typical features of NGLY1 Deficiency Disorder include abnormal tear production, a movement disorder (choreoathetosis), and liver disease. Additional features may include developmental delay, hypotonia (weak muscle tone), peripheral neuropathy, EEG abnormalities, and a small head size (microcephaly)
• The condition is caused by mutations in the N-glycanase 1 gene (NGLY1 gene) and is inherited in an autosomal recessive manner

(Source: Deficiency of N-Glycanase 1; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Deficiency of N-Glycanase 1? (Age and Sex Distribution)

• Deficiency of N-Glycanase 1 is a rare congenital disorder. The presentation of symptoms may occur in the first few months after birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Deficiency of N-Glycanase 1? (Predisposing Factors)

• A positive family history may be an important risk factor, since Deficiency of N-Glycanase 1 can be inherited
• Currently, no other risk factors have been clearly identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Deficiency of N-Glycanase 1? (Etiology)

• Deficiency of N-Glycanase 1 is caused by mutation(s) in the NGLY1 gene, located in the short arm of chromosome 3
  • This gene codes for an enzyme called N-glycanase 1, which removes sugar molecules known as glycans from wrongly folded proteins
  • When the gene is mutated, the abnormal proteins accumulate instead of getting destroyed
• NGLY1 gene mutations resulting in Deficiency of N-Glycanase 1 are inherited in an autosomal recessive manner

Autosomal recessive pattern of inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Deficiency of N-Glycanase 1?

The signs and symptoms of Deficiency of N-Glycanase 1 may include:

• Developmental delay
• Small hands and feet
• Hypotonia (low muscle tone)
• Involuntary movements (choreoathetosis), which may include contractions and twisting movements
• Poor tear production
• Abnormal eye movements
• Microcephaly
• Liver disease
• Peripheral neuropathy
• Seizures that are not completely controlled by medication

How is Deficiency of N-Glycanase 1 Diagnosed?

Deficiency of N-Glycanase 1 is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm NGLY1 gene mutations

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Deficiency of N-Glycanase 1?

The complications of Deficiency of N-Glycanase 1 may include:

• Non-development of speech
• Problems with movement
• Progressive deterioration of liver function
• Encephalopathy
• Risk of injury due to seizures
• Reduced quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Deficiency of N-Glycanase 1 Treated?

There is no cure for Deficiency of N-Glycanase 1, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Deficiency of N-Glycanase 1 be Prevented?

Deficiency of N-Glycanase 1 may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Deficiency of N-Glycanase 1? (Outcomes/Resolutions)

• The prognosis of Deficiency of N-Glycanase 1 is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Deficiency of N-Glycanase 1:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/