Congenital disorder of glycosylation is an inherited condition involving a disruption in how sugar chains form or attach to proteins. These congenital disorders may affect patients ranging from infancy to adulthood. Researchers have identified 19 separate syndromes, each having distinct genetic abnormalities and different symptoms. Treatment generally involves supportive care, depending on the age of the patient and the symptoms presented.
Glycosylation is the process of building long chain sugars that attach to proteins, forming glycoproteins. Dozens of enzymes are responsible for this process. When enzymes malfunction because of a genetic defect, these chains are not properly completed, attached to proteins, or removed when necessary. The abnormality occurs in the N-linked oligosaccharide, which involves every bodily cell. Symptoms related to congenital disorder of glycosylation depend on what body systems become affected by protein instability and miscommunication within and between cells.
Infants and children suffering from versions of the disorder generally grow and develop more slowly than other children of the same age because of an inability to feed. Children may exhibit hypoglycemia along with gastrointestinal disorders that include liver disease. Pediatric patients may bleed easily and have crossed eyes and poor motor development caused by muscle weakness. Youngsters may develop spastic or tremor-like movements. These patients may develop seizures, stroke-like symptoms, or an appearance of mental impairment.
Adolescents and adults with congenital disorder of glycosylation may experience difficulties with balance, physical movement, and speech that are secondary to muscular impairment. The abnormal glycosylation process may inhibit puberty in young female patients, and patients may develop retinitis pigmentosa or suffer from curvature of the spine that progresses over time.
Individuals experiencing symptoms typically undergo a blood test called the carbohydrate deficient transferrin. This test assesses the glycosylation status of transferrin (TF). Using isoelectric focusing or electrospray ionization-mass spectrometry, lab specialists identify abnormal TF patterns. After receiving a definitive diagnosis of congenital disorder of glycosylation, patients undergo further testing that determines specific type. Typing the disorder generally involves assessing enzyme activity for known defects or analyzing blood samples for specific gene mutations.
Infants and children who exhibit failure to thrive syndromes may require high calorie formulas. When the condition affects the ability to consume food orally, gastric feeding tubes may be required. Patients experiencing hypothyroidism secondary to the disorder generally receive replacement medication. Individuals who develop seizure disorders usually require antiseizure medications, and patients with muscular motor impairment, speech, or visual difficulties typically require occupational and physical therapy.