What is Congenital Disorder of Glycosylation, ALG6-related? Congenital disorder of glycosylation, ALG6-related, also known as ALG6-CDG, is a condition characterized by developmental delay and low muscle tone. It is caused by harmful genetic changes (variants) in the ALG6 gene. ALG6 plays an important role in adding sugar molecules to the proteins and fats of the cells (a process known as glycosylation). Harmful genetic changes in ALG6 disrupt this process, leading to the symptoms seen with ALG6-CDG. Symptoms of ALG6-CDG typically begin in infancy. The condition affects many systems of the body, particularly the nervous system, resulting in poor muscle tone, developmental delay, behavioral problems, and intellectual disability in almost all cases. Brain abnormalities, impaired ability to coordinate movement, and seizures are also common. Many affected individuals have poor growth, autistic or behavioral problems, unique facial characteristics, and skeletal abnormalities. Skeletal abnormalities include shortening of fingers and toes, limited joint extension, short arms, and scoliosis. Other symptoms, like bleeding problems, enlarged liver and spleen, enlarged heart, protein loss in the intestines, or pubertal abnormalities, may occur but are less typical. How common is Congenital Disorder of Glycosylation, ALG6-related? The exact incidence of ALG6-CDG is unknown. Approximately 100 individuals have been diagnosed worldwide. To date, the majority of reported cases of ALG6-CDG are in individuals of European ancestry. How is Congenital Disorder of Glycosylation, ALG6-related treated? There is no cure for ALG6-CDG. Treatment for the condition is directed at managing the specific symptoms an individual has. Common interventions may include medications to control seizures and nutritional support to help with growth. Some individuals may need a feeding tube. Individuals diagnosed with ALG6-CDG will often benefit from receiving early intervention and other supportive services beginning at a young age. What is the prognosis for an individual with Congenital Disorder of Glycosylation, ALG6-related? Some individuals with ALG6-CDG die in infancy or early childhood, often due to infection, seizures, or protein loss in the intestines. Most individuals who live into adulthood will require a wheelchair. Adults are unlikely to be able to live independently, but most will be able to speak, albeit with some impairment. Other names forcongenital disorder of glycosylation, ALG6-related ALG6-CDG CDG type 1c Carbohydrate-deficient glycoprotein syndrome type 1C (CDGS1c) Carbohydrate-deficient glycoprotein syndrome type Ic Carbohydrate-deficient glycoprotein syndrome type V Congenital disorder of glycosylation 1c (CDG1c) congenital disorder of glycosylation type Ic References Chang et al., 2018, Ann Transl Med, 6(24):477, PMID: 30740408 Francisco et al., 2023, Orphanet J Rare Dis, 18(1):329, PMID: 37858231 Jaeken et al., 2014, Eur J Hum Genet, 23(2), PMID: 25052310 Morava et al., 2016, J Inherit Metab Dis, 39(5):713-23, PMID: 27287710 Piedade et al., 2022, J Rare Dis, 1:3, https://doi.org/10.1007/s44162-022-00003-6 Sparks et al., 2017, https://www.ncbi.nlm.nih.gov/books/NBK1332/