Also known as FUT8 deficiency
A rare, multisystemic, inherited disorder caused by an abnormal enzyme which disrupts N-linked glycosylation. Symptoms manifest in infancy, including frequent seizures, hypotonia (low muscle tone), developmental delay, failure to thrive, skeletal abnormalities, facial dysmorphism (abnormal difference in structure), respiratory and intestinal problems, and brain, heart, kidney, and eye abnormalities.
Symptoms
FUT8-CDG is an extremely rare inherited condition that affects multiple parts of the body. Affected individuals typically develop signs and symptoms of the condition during early infancy. FUT8-CDG is a severe disorder, which primarily leads to neurologic symptoms: Frequent and characteristic symptoms are seizures, decreased muscle tone (hypotonia), developmental delay and intellectual disability. Feeding difficulties can lead to a failure to gain weight, and patients often grow at a slower rate than normal (failure to thrive). The patients show distinct facial features: common are low-set ears, a broad nasal bridge, prominent skin folds of the upper eyelid that cover the inner corner of the eye (epicanthal folds), an arched palate, a broad forehead, bitemporal narrowing of the skull, enlargement of the eyes (buphthalmos), a short nose, a lower jaw that is positioned more to the back (retrognathia), and excessive hair growth in uncommon places (hirsutism). Additionally, all described patients have presented with an abnormally small head (microcephaly), skeletal abnormalities, respiratory symptoms and intestinal abnormalities. Some patients have been described with strabismus, congenital glaucoma and abnormalities of the kidneys and the heart. Brain imaging often shows abnormalities but can also be normal. Some patients are so severely affected by the disorder that they may die in early childhood. Laboratory investigations sometimes show hormonal disturbances, like an underactive thyroid (hypothyroidism) or low blood glucose (hypoglycemia), as well as abnormalities of the components of the blood (hematologic abnormalities).
There are nine individuals with FUT8-CDG published in medical literature.
Diagnosis
The glycosylation of transferrin, which is often used as a screening method for CDG, is normal in FUT8-CDG. However, the analysis of sugar chains attached to proteins in the blood (serum N-glycans) can detect the disorder, which can be done by different methods in blood and fibroblasts. Genetic testing is needed to confirm the diagnosis. Individuals with FUT8-CDG have two faulty copies of the FUT8 gene.
Treatment and Prognosis
To date, there are no FDA-approved treatment options available for FUT8-CDG. Treatment is aimed at the management of symptoms and the prevention of complications. Oral supplementation with the dietary sugar L-fucose has led to clinical improvement in twins with a severe phenotype of FUT8-CDG, however, this has not yet been investigated in formal clinical trials.
Most diagnosed FUT8-CDG patients are still young, which makes long-term prognosis difficult. The oldest individual with FUT8-CDG that has been described in medical literature is 17 years old.