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Year : 2017  |  Volume : 6  |  Issue : 4  |  Page : 228-229

Imerslund-Grasbeck syndrome presenting as pancytopenia: A rare case report

Department of Medicine, Dr. Yashwant Singh Parmar Government Medical College, Nahan, Himachal Pradesh, India

Date of Web Publication12-Dec-2017

Correspondence Address:
Dr. Pravesh Agarwal
H.N. 1652/6, Near S.E.P.W.D, Circle Office, Nahan, District-Sirmour, Himachal Pradesh - 173 001
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijhas.IJHAS_30_17

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Imerslund-Grasbeck syndrome or selective Vitamin B12 malabsorption with proteinuria or megaloblastic anemia 1 is a rare autosomal recessive disorder. The main feature of this condition is megaloblastic anemia due to Vitamin B12 deficiency with or without persistent proteinuria (with no signs of kidney disease). The disease appears from 4 months up to several years after birth. The cause is a defect in the receptor of the Vitamin B12-intrinsic factor complex of the ileal enterocytes. Management includes lifelong parenteral Vitamin B12, and with this, the patients remain healthy for decades. However, the proteinuria persists. We present a 14-year-old male child suffering from this syndrome presenting to us with pancytopenia due to Vitamin B12 deficiency and proteinuria with normal kidneys. There is hardly any case report of this syndrome from North India.

Keywords: Imerslund-Grasbeck syndrome, pancytopenia, proteinuria, Vitamin B12deficiency

How to cite this article:
Agarwal P, Chand S, Pandey D. Imerslund-Grasbeck syndrome presenting as pancytopenia: A rare case report. Int J Health Allied Sci 2017;6:228-9

How to cite this URL:
Agarwal P, Chand S, Pandey D. Imerslund-Grasbeck syndrome presenting as pancytopenia: A rare case report. Int J Health Allied Sci [serial online] 2017 [cited 2024 Feb 24];6:228-9. Available from: https://www.ijhas.in/text.asp?2017/6/4/228/220522

  Introduction Top

Imerslund-Grasbeck syndrome (IGS) is a rare disorder characterized by Vitamin B12 deficiency due to selective malabsorption resulting in megaloblastic anemia appearing in childhood (but not immediately after birth as in transcobalamin deficiency).[1] Prevalence is about 1:200,000 in Finland and Norway where it was first described.[1],[2] About 400 case reports are published worldwide.[2] There is hardly any report of this syndrome presenting as pancytopenia from North India. Hence, we report this rare case of pancytopenia, Vitamin B12 deficiency, and proteinuria with normal kidneys presented in our institute.

  Case Report Top

A 14-year-old male child from Himachal Pradesh (North India) presented to us with a history of easy fatigue ability and shortness of breath on mild exertion for the last 3 months. There was neither any history suggestive of cardiovascular, renal, or hepatic disease nor any history of blood loss. There was no significant family history. On examination, he had gross pallor and mild hepatomegaly with no other relevant findings.

His investigations revealed [Table 1] severe anemia, decreased total leukocyte count, and decreased platelets-pancytopenia. Peripheral smear showed macrocytes, macro-ovalocytes, tear drop cells, few nucleated red blood cells, leukopenia, and reduced platelets. His serum ferritin levels were normal. Vitamin B12 levels were found to be low. Serum folic acid levels were normal. Bone marrow was suggestive of megaloblastic hematopoiesis. His liver function tests showed hemolytic picture. On urine examination, protein was detected and his 24 h urinary proteins were raised. Renal function tests were normal. His abdominal ultrasonography and chest X-ray were normal. Antiparietal cell antibody and anti-intrinsic factor antibody were also not detected ruling out the possibility of pernicious anemia. Hence, we found only pancytopenia, mild hemolysis, proteinuria with normal kidneys, and low levels of Vitamin B12 – a diagnosis of IGS was made. He was treated with daily intramuscular injections of Vitamin B12 for 7 days and then weekly for 6 weeks. He was advised monthly injections thereafter. His hemoglobin level rose, and there was increase in platelets and leukocytes but proteinuria persisted.
Table 1: Investigation reports with reference range

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  Discussion Top

IGS is a rare autosomal recessive disorder, which means that both copies of gene in each cell have mutations. The cause is a defect in the receptor of the Vitamin B12-intrinsic factor complex of the ileal enterocyte. In most cases, there are mutations in one of two genes, cubilin on chromosome 10 or amnionless (amphotericin B) on chromosome 14.[1] Both proteins are components of the intestinal receptor for the Vitamin B12-intrinsic factor complex and the receptor mediating the tubular reabsorption of protein from urine.[1] Patients usually present with megaloblastic anemia due to selective malabsorption of Vitamin B12. Proteinuria is present in about 50%–70% cases.[2],[3] Proteinuria is neither typically glomerular nor tubular.[1],[2],[3] Proteinuria persists over the years, and kidney function remains normal. It is prudent to note that in IGS, there is no deficiency of intrinsic factor or the Vitamin B12-intrinsic factor complex. The defect is in the uptake of the complex by the ileal receptors. This has been proved by classic Schilling's test.[4],[5]

The diagnosis of IGS requires (1) young patient with Vitamin B12 deficiency which is due to malabsorption, (2) with or without proteinuria, with normal kidneys, (3) by showing that the condition is reversed by parenteral Vitamin B12.[2] Most common presentation of Vitamin B12 deficiency is megaloblastic anemia. Hemolysis and pancytopenia can be a part of Vitamin B12 deficiency due to ineffective erythropoiesis.[6] There is hardly any case report of this syndrome presenting as pancytopenia from North India. Hence, we presented this case. Hence, in every young patient with pancytopenia, we must exclude Vitamin B12 deficiency. Once a patient is diagnosed with IGS, lifelong parenteral Vitamin B12 is to be given. Prognosis is excellent with Vitamin B12 supplementation. However, the patient continues to have proteinuria without any renal damage.

Hence, in spite of the absence of genetic tests, taking into account clinical symptoms, laboratory tests, and response to parenteral treatment with cobalamin (Vitamin B12), IGS can be recognized with high probability.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Gräsbeck R. Imerslund-Gräsbeck syndrome (selective Vitamin B(12) malabsorption with proteinuria). Orphanet J Rare Dis 2006;1:17.  Back to cited text no. 1
Shetty Manohar G. Pancytopenia with proteinuria- Imerslund Grasbeck syndrome. Int J Biomed Res 2012;3:56-7.  Back to cited text no. 2
Karatekin G, Sezgin B, Kayaoblu S, Nuhoglu A. Imerlund- Grasbeck syndrome. Indian Paediatr 1999;36:1262-4.  Back to cited text no. 3
Brada N, Gordon MM, Wen J, Alpers DH. Transfer of cobalamin from intrinsic factor to transcobalamin II. J Nutr Biochem 2001;12:200-6.  Back to cited text no. 4
Tanner SM, Li Z, Perko JD, Oner C, Cetin M, Altay C, et al. Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene. Proc Natl Acad Sci U S A 2005;102:4130-3.  Back to cited text no. 5
Cetinkaya F, Yildirmak Y, Kutluk G, Erdem E. Nutritional Vitamin B12 deficiency in hospitalized young children. Pediatr Hematol Oncol 2007;24:15-21.  Back to cited text no. 6


  [Table 1]

This article has been cited by
1 Imerslund-Gräsbeck syndrome: a comprehensive review of reported cases
Sandra D.K. Kingma, Julie Neven, An Bael, Marije E.C. Meuwissen, Machiel van den Akker
Orphanet Journal of Rare Diseases. 2023; 18(1)
[Pubmed] | [DOI]


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