Congenital disorder of glycosylation with defective fucosylation 1 is a multisystem condition that primarily affects growth and neurodevelopment. The disorder is characterized by abnormal glycosylation processes due to disruptions in fucosylation, with the FUT8 gene being the sole gene implicated in its etiology. Affected children typically present early in life with failure to thrive and significant developmental delays, including intellectual disability and seizures. Although precise prevalence data are not available, the constellation of symptoms indicates a serious impact on multiple organ systems.

The clinical presentation of this condition is broad and involves several interconnected systems. Neurologically, affected children demonstrate severe global developmental delay, intellectual disability, and seizures, highlighting the impact on cognitive function and brain development. In addition, these individuals frequently exhibit signs such as hypotonia, microcephaly, and feeding difficulties, which together contribute to challenges in achieving developmental milestones. From a growth perspective, common features include failure to thrive, limb undergrowth, short stature, and intrauterine growth retardation. Other variable findings observed in a subset of cases include osteopenia, certain craniofacial differences such as a broad or narrow forehead and wide nasal bridge, as well as cardiac issues like a patent ductus arteriosus. Not all individuals experience every symptom, and severity varies considerably between patients, underscoring the complex nature of the disorder.

This condition is caused by pathogenic variants in the FUT8 gene, which plays a critical role in the process of fucosylation, a type of glycosylation important for correct protein function. Disruption in this enzyme’s activity leads to improperly modified proteins, affecting a variety of systems in the body. The disorder is inherited in an autosomal recessive pattern, meaning that an affected individual has received one altered copy of the gene from each parent. In families where both parents carry a variant in FUT8, there is an increased likelihood of having an affected child, and genetic counseling is recommended to discuss recurrence risks and implications for family planning. Associated genes include FUT8.