Congenital disorders of glycosylation (CDG) encompass a group of conditions affecting glycosylation, a critical process diversifying protein functions in the body. CDG-Ic impacts multiple body systems, particularly the nervous system, leading to common symptoms like low muscle tone, developmental delays, and intellectual disabilities.
Brain malformations, coordination difficulties, and seizures are prevalent. Many affected individuals experience growth problems, behavioral issues, and distinct physical and skeletal abnormalities. These physical traits include deep-set eyes, a narrowed forehead, a broad nasal bridge, a shortened upper lip area, and widely spaced eyes. Skeletal issues involve finger and toe shortening, restricted joint movement, short arms, and scoliosis. Although less common, additional symptoms like deep vein thrombosis, enlarged liver and spleen, enlarged heart, intestinal protein loss, or pubertal irregularities may also occur. Up to 25% of people with CDG-Ic die in infancy or early childhood. Most individuals that live into adulthood will require a wheelchair.
CDG-Ic is caused by pathogenic (disease-causing) variants in the ALG6 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a 1 in 1671 chance to be a carrier.
Other names for this condition are carbohydrate-deficient glycoprotein syndrome type Ic, carbohydrate-deficient glycoprotein syndrome type V, and glucosyltransferase 1 deficiency.