Research Report

JIMD Reports - Case and Research Reports, 2012/4

Volume 7 of the series JIMD Reports pp 13-18

Date:

Hereditary Intrinsic Factor Deficiency in Chaldeans

  • Amy C. SturmAffiliated withHuman Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State UniversityHuman Genetics, Department of Internal Medicine, The Ohio State University
  • , Elizabeth C. BaackAffiliated withHuman Genetics, Department of Internal Medicine, The Ohio State University
  • , Michael B. ArmstrongAffiliated withDivision of Hematology-Oncology, Department of Pediatrics, Duke University
  • , Deborah SchiffAffiliated withDivision of Hematology/Oncology, Rady Children’s Hospital, UCSD School of Medicine
  • , Ayesha ZiaAffiliated withDivision of Hematology/Oncology, Children’s Hospital of Michigan, Wayne State University School of Medicine
  • , Sureyya SavasanAffiliated withDivision of Hematology/Oncology, Children’s Hospital of Michigan, Wayne State University School of Medicine
  • , Albert de la ChapelleAffiliated withHuman Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University
  • , Stephan M. TannerAffiliated withHuman Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University Email author 

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Abstract

Juvenile vitamin B12 or cobalamin (Cbl) deficiency is notoriously difficult to explain due to numerous acquired and inherited causes. The consequences of insufficient Cbl are megaloblastic anemia, nutrient malabsorption, and neurological problems. The treatment is straightforward with parenteral Cbl supplementation that resolves most health issues without an urgent need to clarify their cause. Aside from being clinically unsatisfying, failing to elucidate the basis of Cbl deficiency means important information regarding recurrence risk is not available to the individual if the cause is contagious or inherited. Acquired causes have largely disappeared in the Modern World because they were mostly due to parasites or malnutrition. Today, perhaps the most common causes of juvenile Cbl deficiency are Imerslund-Gräsbeck syndrome and inherited intrinsic factor deficiency (IFD). Three genes are involved and genetic testing is complicated and not widely available. We used self-identified ancestry to accelerate and confirm the genetic diagnosis of IFD in three families of Chaldean origin. A founder mutation limited to Chaldeans from Iraq in the intrinsic factor gene GIF was identified as the cause. World events reshape the genetic structure of populations and inherited diseases in many ways. In this case, all the patients were diagnosed in the USA among recent immigrants from a single region. While IFD itself is not restricted to one kind of people, certain mutations are limited in their range but migrations relocate them along with their host population. As a result, self-identified ancestry as a stratifying characteristic should perhaps be considered in diagnostic strategies for rare genetic disorders.