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ALG6-congenital disorder of glycosylation

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Description

ALG6-congenital disorder of glycosylation (ALG6-CDG, also known as congenital disorder of glycosylation type Ic) is an inherited condition that affects many parts of the body. The signs and symptoms of ALG6-CDG vary widely among people with the condition.

Individuals with ALG6-CDG typically develop signs and symptoms of the condition during infancy. They may have difficulty gaining weight and growing at the expected rate (failure to thrive). Affected infants often have weak muscle tone (hypotonia) and developmental delay.

People with ALG6-CDG may have seizures, problems with coordination and balance (ataxia), or stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. They may also develop blood clotting disorders. Some individuals with ALG6-CDG have eye abnormalities including eyes that do not look in the same direction (strabismus) and an eye disorder called retinitis pigmentosa, which causes vision loss. Females with ALG6-CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, most females with ALG6-CDG do not go through puberty.

Frequency

The prevalence of ALG6-CDG is unknown, but it is thought to be the second most common type of congenital disorder of glycosylation. More than 30 cases of ALG6-CDG have been described in the scientific literature.

Causes

ALG6-CDG is caused by mutations in the ALG6 gene. This gene provides instructions for making an enzyme that is involved in a process called glycosylation. Glycosylation is the process by which sugar molecules (monosaccharides) and complex chains of sugar molecules (oligosaccharides) are added to proteins and fats. Glycosylation modifies proteins and fats so they can perform a wider variety of functions. The enzyme produced from the ALG6 gene transfers a simple sugar called glucose to the growing oligosaccharide. Once the correct number of sugar molecules are linked together, the oligosaccharide is attached to a protein or fat.

ALG6 gene mutations lead to the production of an abnormal enzyme with reduced or no activity. Without a properly functioning enzyme, glycosylation cannot proceed normally, and oligosaccharides are incomplete. As a result, glycosylation is reduced or absent. The wide variety of signs and symptoms in ALG6-CDG are likely due to impaired glycosylation of proteins and fats that are needed for normal function in many organs and tissues, including the brain, eyes, liver, and hormone-producing (endocrine) system.

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

  • ALG6-CDG
  • carbohydrate-deficient glycoprotein syndrome type Ic
  • carbohydrate-deficient glycoprotein syndrome type V
  • CDG syndrome type Ic
  • CDG1C
  • CDGIc
  • congenital disorder of glycosylation type Ic
  • glucosyltransferase 1 deficiency

Additional Information & Resources

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Research Studies from ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Damen G, de Klerk H, Huijmans J, den Hollander J, Sinaasappel M. Gastrointestinal and other clinical manifestations in 17 children with congenital disorders of glycosylation type Ia, Ib, and Ic. J Pediatr Gastroenterol Nutr. 2004 Mar;38(3):282-7. Citation on PubMed
  • Grünewald S, Imbach T, Huijben K, Rubio-Gozalbo ME, Verrips A, de Klerk JB, Stroink H, de Rijk-van Andel JF, Van Hove JL, Wendel U, Matthijs G, Hennet T, Jaeken J, Wevers RA. Clinical and biochemical characteristics of congenital disorder of glycosylation type Ic, the first recognized endoplasmic reticulum defect in N-glycan synthesis. Ann Neurol. 2000 Jun;47(6):776-81. Citation on PubMed
  • Imbach T, Burda P, Kuhnert P, Wevers RA, Aebi M, Berger EG, Hennet T. A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6982-7. Citation on PubMed or Free article on PubMed Central
  • Imbach T, Grünewald S, Schenk B, Burda P, Schollen E, Wevers RA, Jaeken J, de Klerk JB, Berger EG, Matthijs G, Aebi M, Hennet T. Multi-allelic origin of congenital disorder of glycosylation (CDG)-Ic. Hum Genet. 2000 May;106(5):538-45. Citation on PubMed
  • Sparks SE, Krasnewich DM. Congenital Disorders of N-Linked Glycosylation and Multiple Pathway Overview. 2005 Aug 15 [updated 2017 Jan 12]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1332/ Citation on PubMed
  • Westphal V, Xiao M, Kwok PY, Freeze HH. Identification of a frequent variant in ALG6, the cause of Congenital Disorder of Glycosylation-Ic. Hum Mutat. 2003 Nov;22(5):420-1. Citation on PubMed
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