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ALG12-congenital disorder of glycosylation
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

ALG12-congenital disorder of glycosylation

ALG12‑CDG is a rare autosomal‑recessive disorder that impairs protein and lipid glycosylation, leading to multisystem problems such as failure to thrive, developmental delay, hypotonia, and immune deficiency.

Overview

ALG12-congenital disorder of glycosylation (ALG12-CDG, also known as congenital disorder of glycosylation type Ig) is an inherited disorder with varying signs and symptoms that can affect several body systems. Individuals with ALG12-CDG typically develop signs and symptoms of the condition during infancy. They may have problems feeding and difficulty growing and gaining weight at the expected rate (failure to thrive). In addition, affected individuals often have intellectual disability, delayed development, and weak muscle tone (hypotonia), and some develop seizures.

Symptoms

  • Feeding difficulties and failure to thrive
  • Intellectual disability and delayed developmental milestones
  • Weak muscle tone (hypotonia)
  • Seizures
  • Microcephaly (small head size)
  • Facial dysmorphism: epicanthal folds, prominent nasal bridge, abnormally shaped ears
  • Male genital anomalies: micropenis, undescended testes
  • Reduced immunoglobulin G (IgG) levels (hypogammaglobulinemia)
  • Cardiomyopathy (weakened heart muscle) – less common
  • Skeletal abnormalities due to poor bone development – less common

Causes & Risk Factors

Mutations in the ALG12 gene cause ALG12-CDG. This gene provides instructions for making an enzyme that is involved in a process called glycosylation. During this process, complex chains of sugar molecules (oligosaccharides) are added to proteins and fats (lipids). Glycosylation modifies proteins and lipids so they can fully perform their functions. The enzyme produced from the ALG12 gene transfers a simple sugar called mannose to growing oligosaccharides at a particular step in the formation of the sugar chain. Once the correct number of sugar molecules are linked together, the oligosaccharide is attached to a protein or lipid.

ALG12 gene mutations lead to the production of an abnormal enzyme with reduced activity. Without a properly functioning enzyme, mannose cannot be added to the chain efficiently, and the resulting oligosaccharides are often incomplete. Although the short oligosaccharides can be transferred to proteins and fats, the process is not as efficient as with the full‑length oligosaccharide. As a result, glycosylation is reduced. The wide variety of signs and symptoms in ALG12-CDG are likely due to impaired glycosylation of proteins and lipids that are needed for normal function of many organs and tissues, including the brain.

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

  • ALG12‑CDG
  • CDG Ig
  • CDG1G
  • Congenital disorder of glycosylation type 1G
  • Congenital disorder of glycosylation type Ig

Additional Information & Resources

Genetic Testing Information

  • Genetic Testing Registry: ALG12-congenital disorder of glycosylation

Genetic and Rare Diseases Information Center

  • ALG12‑CDG
  • Congenital disorder of glycosylation

Patient Support and Advocacy Resources

  • National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

  • CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ig; CDG1G

Scientific Articles on PubMed

  • PubMed

References

  • Chantret I, Dupre T, Delenda C, Bucher S, Dancourt J, Barnier A, Charollais A, Heron D, Bader‑Meunier B, Danos O, Seta N, Durand G, Oriol R, Codogno P, Moore SE. Congenital disorders of glycosylation type Ig is defined by a deficiency in dolichyl‑P‑mannose:Man7GlcNAc2‑PP‑dolichyl mannosyltransferase. J Biol Chem. 2002 Jul 12;277(28):25815‑22. doi: 10.1074/jbc.M203285200.
  • Grubenmann CE, Frank CG, Kjaergaard S, Berger EG, Aebi M, Hennet T. ALG12 mannosyltransferase defect in congenital disorder of glycosylation type Ig. Hum Mol Genet. 2002 Sep 15;11(19):2331‑9. doi: 10.1093/hmg/11.19.2331.
  • Kranz C, Basinger AA, Gucsavas‑Calikoglu M, Sun L, Powell CM, Henderson FW, Aylsworth AS, Freeze HH. Expanding spectrum of congenital disorder of glycosylation Ig (CDG‑Ig): sibs with a unique skeletal dysplasia, hypogammaglobulinemia, cardiomyopathy, genital malformations, and early lethality. Am J Med Genet A. 2007 Jun 15;143A(12):1371‑8. doi: 10.1002/ajmg.a.31791.
  • Murali C, Lu JT, Jain M, Liu DS, Lachman R, Gibbs RA, Lee BH, Cohn D, Campeau PM. Diagnosis of ALG12‑CDG by exome sequencing in a case of severe skeletal dysplasia. Mol Genet Metab Rep. 2014;1:213‑219. doi: 10.1016/j.ymgmr.2014.04.004.
  • Thiel C, Schwarz M, Hasilik M, Grieben U, Hanefeld F, Lehle L, von Figura K, Korner C. Deficiency of dolichyl‑P‑Man:Man7GlcNAc2‑PP‑dolichyl mannosyltransferase causes congenital disorder of glycosylation type Ig. Biochem J. 2002 Oct 1;367(Pt 1):195‑201. doi: 10.1042/BJ20020794.

Frequently Asked Questions

Parents might notice significant feeding difficulties, a failure to gain weight or grow at the expected rate (failure to thrive), and generalized weak muscle tone (hypotonia), making the baby seem "floppy." Developmental delays, such as not reaching milestones like sitting or rolling over on time, and sometimes seizures, can also be early indicators of ALG12-CDG.
The long-term prognosis for individuals with ALG12-CDG varies, but many face lifelong challenges with intellectual disability, developmental delays, and muscle weakness. Ongoing care requires a multidisciplinary team, including neurologists, gastroenterologists, immunologists, cardiologists, and developmental therapists. Regular monitoring for complications like seizures, infections, and heart problems is essential to optimize quality of life and manage symptoms as they evolve.
Diagnosis often begins with observing the characteristic clinical symptoms. Initial screening tests may include a blood test called transferrin isoelectric focusing (TIEF), which can detect abnormal glycosylation patterns. A definitive diagnosis is confirmed through genetic testing, which analyzes the ALG12 gene for specific mutations known to cause the disorder.
Treatment for ALG12-CDG is primarily supportive and symptomatic, as there is no cure. This includes nutritional support to address failure to thrive, often with specialized feeding plans or tubes. Physical, occupational, and speech therapies are crucial for developmental delays and hypotonia. Seizures are managed with anti-epileptic medications, and individuals with reduced immunoglobulin G (IgG) levels may receive immunoglobulin replacement therapy to bolster their immune system. Regular monitoring for heart and skeletal issues is also part of comprehensive care.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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