National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Imerslund-Grasbeck syndrome


Other Names:
IGS; Pernicious anemia, juvenile, due to selective intestinal malabsorption of vitamin B12, with proteinuria; Enterocyte cobalamin malabsorption; IGS; Pernicious anemia, juvenile, due to selective intestinal malabsorption of vitamin B12, with proteinuria; Enterocyte cobalamin malabsorption; Defect of enterocyte intrinsic factor receptor; Familial megaloblastic anemia; Selective cobalamin malabsorption with proteinuria; Gräsbeck-Imerslund disease; Megaloblastic anemia 1 See More
Categories:
Imerslund-Grasbeck syndrome (IGS) is a rare condition characterized by vitamin B12 deficiency, often causing megaloblastic anemia. IGS usually appears in childhood. Other features may include failure to thrive, infections, and neurological damage. Mild proteinuria (with no signs of kidney disease) is present in about half of affected individuals. IGS is caused by mutations in either the CUBN or AMN gene and is inherited in an autosomal recessive manner. Treatment includes life-long vitamin B12 injections, with which affected individuals can stay healthy for decades.[1]
Last updated: 1/6/2014
Affected individuals often first experience non-specific health problems, such as failure to thrive and grow, recurrent gastrointestinal or respiratory infections, pallor and fatigue. Individuals often have anemia, and about half of affected individuals also have mild proteinuria but no signs of kidney disease. Individuals may also have mild neurological damage. Congenital (present at birth) abnormalities of the urinary tract were present in some of the original reported cases. The age at diagnosis is usually anywhere from a few months of age to about 14 years of age.[2][3]
Last updated: 1/6/2014

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 10 |
Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance 0000007
Childhood onset
Symptoms begin in childhood
0011463
Confusion
Disorientation
Easily confused
Mental disorientation
[ more ] 		0001289
Dementia
Dementia, progressive
Progressive dementia
[ more ] 		0000726
Malabsorption of Vitamin B12 0200118
Megaloblastic anemia 0001889
Paresthesia
Pins and needles feeling
Tingling
[ more ] 		0003401
Proteinuria
High urine protein levels
Protein in urine
[ more ] 		0000093
Sensory impairment 0003474
Vitamin B12 deficiency 0100502
Showing of 10 |
Last updated: 7/1/2020
The diagnosis of Imerslund-Grasbeck syndrome (IGS) is made after a series of tests are performed. Cobalamin deficiency is typically detected first, followed by showing that cobalamin is poorly absorbed (the main cause of cobalamin deficiency). Other known causes of vitamin B12 malabsorption must then be ruled out. Lastly, it must be shown that after correcting the deficiency, the only nutrient to be poorly absorbed is vitamin B12. The diagnosis can also be confirmed by having genetic testing of the genes that are known to cause the condition. While the presence of proteinuria is strongly suggestive of IGS, not all affected individuals have proteinuria.[2]
Last updated: 1/6/2014

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Imerslund-Grasbeck syndrome. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Imerslund-Grasbeck syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • Is it possible for it to go undiagnosed into adulthood or for symptoms not to start until adulthood - say late 20's? See answer


  1. Grasbeck R. Imerslund-Grasbeck syndrome. Orphanet. May 2006; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=35858. Accessed 7/6/2011.
  2. Ralph Gräsbeck. Imerslund-Gräsbeck syndrome (selective vitamin B12 malabsorption with proteinuria). Orphanet J Rare Dis. May 19, 2006; 1(17):Accessed 1/6/2014.
  3. Ralph Gräsbeck. Gräsbeck-Imerslund disease. Orphanet. May, 2006; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=35858. Accessed 1/6/2014.