Also known as Congenital Disorder of Glycosylation Type Id
A rare, multisystemic disorder beginning in infancy. It is characterized by severe neurological involvement, such as decreased muscle tone, developmental delay, intellectual disability, hearing loss, progressive brain atrophy, seizures, unusual facial features, vision problems, recurrent infections, and musculoskeletal, heart, lung, kidney, and urogenital abnormalities.
ALG3-CDG is a rare autosomal recessive disorder currently reported in 43 cases throughout medical literature. Signs and symptoms typically develop during infancy and affect many body systems throughout life. Individuals have variable degrees of developmental delay and intellectual disability and can have abnormally small heads, which are present at birth or develop during early infancy. Neurological involvement can lead to reduced brain volume, epilepsy, and low muscle tone. Eye abnormalities are common and most often present in the form of unaligned eyes and underdevelopment of the ocular nerve. Variable series of facial features, such as hypertelorism (wide set eyes) or a flat nasal bridge, and gastrointestinal issues similar to other CDGs have often been noted. Immunological involvement resulting in recurrent infections is also common. Musculoskeletal abnormalities such as scoliosis, club feet, and low bone mass have occurred in ALG3-CDG patients. Heart and lung defects are present less often and include widening of the arteries of the heart, thickened heart walls, and underdeveloped lungs. Renal anomalies and other urogenital involvement are seen in a small subset of patients. Sometimes, individuals can present with hormonal abnormalities, hearing loss, and neural tube defects.
Laboratory findings may show elevated levels of the liver protein ALT (indicating hepatopathy), and decreased levels of antithrombin III and factor XI, proteins involved in blood clotting.
Patients are primarily screened by looking at a serum protein called transferrin for abnormal sugar chain patterns on the protein. This often reveals what is known as a type 1 glycosylation pattern. Further analysis of skin cells of patients can reveal an accumulation of shortened sugar chains and a reduction in longer, mature chains on different proteins. Importantly, genetic testing is needed to provide diagnostic certainty by revealing disease causing changes in the ALG3 gene.
Treatment and Prognosis
There are no known treatments for ALG3-CDG. Physical and occupational therapy have been used in patients with skeletal abnormalities. Antiepileptic drugs have been used in conjunction with ketogenic diets to treat epilepsy, however, this has yielded only limited success [2, 4]. Due to the rarity of the disease, there is no clear prognosis. There are ALG3-CDG patients that die soon after birth or are stillbirths, but there are also patients who have lived into their thirties.