congenital disorder of glycosylation with defective fucosylation 2

Congenital disorder of glycosylation with defective fucosylation 2 is a genetic condition affecting multiple organ systems, particularly the central nervous system and musculoskeletal system. It is caused by alterations in the FCSK gene, which produces an enzyme essential for proper glycosylation processes in the body. The condition presents in early childhood with significant neurodevelopmental challenges and physical impairments. While specific prevalence rates are not established, this condition is considered rare.

Individuals with this condition consistently experience severe neurological and physical impairments, including inability to walk, seizures, hypotonia, severe intellectual disability, and global developmental delay. Feeding difficulties, joint contractures, and visual impairment are also always present. Additional features, observed in a significant subset of individuals, include premature birth, abnormalities such as agenesis of the corpus callosum, gastroesophageal reflux, appendicular spasticity, nystagmus, and epileptic encephalopathy. Other variable findings involve delayed central nervous system myelination, cerebellar atrophy, respiratory insufficiency, recurrent respiratory infections, cerebral visual impairment, and periventricular leukomalacia. Not all individuals experience every associated feature, and severity varies considerably.

This condition is linked to pathogenic variants in the FCSK gene, which plays a crucial role in the process of glycosylation by contributing to the addition of fucose residues required for normal cellular function. It is inherited in an autosomal recessive pattern, meaning that an affected individual has inherited two copies of the altered gene, one from each parent. Consequently, parents who share a common ancestor may have an increased likelihood of both being carriers, and there is a 25% chance of recurrence in each pregnancy if both parents carry the variant. Genetic counseling is recommended to help families understand the implications of this inheritance pattern.

Currently, management focuses on supportive care and symptom management, as no treatments have been specifically approved for this condition. Treatment is tailored to each individual and routinely involves a multidisciplinary team that may include neurologists, developmental pediatricians, physical and occupational therapists, and nutrition specialists. Regular surveillance is an essential part of long-term care, helping to identify potential complications early. Genetic counseling is also recommended to provide families with further guidance on the condition and assist in planning for the future.

The course of congenital disorder of glycosylation with defective fucosylation 2 is highly variable, with significant challenges present from early childhood. It is a lifelong neurodevelopmental condition characterized by severe initial impairments, where many children face profound intellectual disability and physical challenges. Outcomes depend on symptom severity, age at diagnosis, and access to specialized, multidisciplinary care, and while medical care has improved over recent decades, the condition may progress, stabilize, or vary considerably among individuals. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with specialists and genetic counselors for ongoing support.