NGLY1
Name of disorder NGLY1 Deficiency [NGLY1-CDDG (congenital disorder of deglycosylation)]
Symptoms

NGLY1-CDDG is an inherited condition that affects many parts of the body. Each child is unique and may or may not have each of the symptoms discussed here. Individuals with NGLY1-CDDG typically develop signs and symptoms of the condition during infancy. Affected infants may have weak muscle tone, a hyperkinetic movement disorder (quivering, twitching or jerking, lack of coordination and accuracy in voluntary movements, head bobbing, or involuntary muscle contractions that force the body into abnormal movements or positions), developmental delay, seizures, dry eyes, and difficulty gaining weight and growing at the expected rate (failure to thrive). Laboratory findings include elevated liver enzymes, abnormal clotting factor activities, and low cholesterol. Hormonal abnormalities, specifically adrenal insufficiency, have also rarely been reported. During childhood, individuals with NGLY1-CDDG often develop reduced sensation and weakness in their arms and legs (peripheral neuropathy), sores on the clear front surface of the eye (corneal ulceration), pigment changes and abnormalities in the cells lining the back of the eye (retinitis pigmentosa and cone dystrophy), eye and eyelid infection or irritation, oral motor difficulties that can affect feeding ability, recurrent interruptions of breathing during sleep (central and obstructive sleep apnea), reduced ability to sweat leading to an increased risk to overheat (hypohydrosis), and an abnormality in the way the brain processes sound (auditory neuropathy). During adolescence they can develop an abnormal curvature of the spine (scoliosis). Young individuals with NGLY1-CDDG who survive infancy may have mild to profound intellectual disability, and many are unable to walk independently. There are less than 100 NGLY1-CDDG patients published in the medical literature.

Diagnosis

The diagnosis of NGLY1-CDDG is established in an individual by the identification of two faulty copies of the NGLY1 gene through genetic testing. Typical blood screening tests for other congenital disorders of glycosylation (i.e., analysis of serum transferrin glycoforms, N and O glycan profiling) will not reliably detect NGLY1-CDDG. Urine oligosaccharides analyzed by a special technique involving mass spectrometry is abnormal in most affected individuals.

Treatment and prognosis

Early death has occurred in a few individuals with NGLY1-CDDG from complications of seizures, adrenal insufficiency, and infection. Life expectancy is unknown at this time. The oldest diagnosed NGLY1-CDDG patient is in her late 20s. There is no curative treatment for NGLY1-CDDG; treatment focuses on the treatment of symptoms and prevention of complications. Several drugs are under investigation in preclinical research studies for the treatment of NGLY1-CDDG.