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Case Reports Indian Pediatrics 1999;36: 1262-1264 |
Imerslund-Grasbeck Syndrome |
Guner Karatekin, Betul Sezgin*, Semra Kayaoglu, Asiye Nuhoglu From the Department of Pediatrics, Sisli Etfal Hospital,
Istanbul, Turkey and *Department of Pediatrics, Vakif Gureba Hospital, Istanbul, Turkey |
| The Imerslund-Grasback syndrome (IGS) is a rare autosomal recessive disease characterized by anemia due to selective vitamin B12 intrinsic factor complex in terminal ileum(1-3). This syndrome is usually accompanied by proteinuria and sometimes by steatorrhea and neurodevelopmental dys-function. This disease has been reported in Middle East and Far East countries as well as in Northern Europe(1,2,4,5). This report presents one such case from Istanbul, Turkey. Case Report A 14-month-old boy was brought to our clinic with the complaints of weakness, cough, vomiting, over sleeping, and fever which had been continuing for two months. The family previously had one child who died at 1 year of age with similar clinical findings. Physical examination revealed a pale boy whose height (72 cm) and weight (8 kg) were at the third percentile. Nostril breathing, intercostal and substernal indrawings were present and bilateral crepitations could be auscultated. The liver was palpable 4 cm below the right and spleen was palpable 2 cm below the left costal margin. His neuromuscular development was consistent with his age. He revealed no sign of hypotonia and hyperreflexia. His mental status was also normal. The remaining systemic examination was unremarkable. In his abdominal ultrasonography, no pathological findings were present except diffuse hepatosplenomegaly. His laboratory tests showed hemoglobin level of 7.1 g/dl, white blood cell count of 9000 per cu mm platelets 168,000 per cumm and a high mean corpuscular volume (MCV) of erythrocytes (109.8 fl). In the peripheral blood smear, macrocytosis of red blood cells and hypersegmented polymorphs were present. Megaloblastic changes were also detected by bone marrow aspiration. The serum iron, iron binding capacities and transferrin were 67 g/dl, 198 g/dl and 300 mg/dl, respectively. Hemoglobin electrophoresis was within normal limits. No parasite was found on stool examination. Proteinuria wasn't detected by urine analysis. The serum folic acid level was 9.1 ng/ml (normal 3-17 ng/ml). The serum Vitamin B12 level was 8 pg/ml (normal 200-950 pg/ml) and the Schilling test showed vitamin B12 malabsorption which was not corrected by the addition of an intrinsic factor (by double bound technique urinary excretion was 1% and 1.2%, respectively). The results of these tests supported vitamin B12 deficiency due to malabsorption. Based on these results the patient was diagnosed as IGS and was given intramuscular Vitamin B12 1mg/day for 15 days. On the 5th day of the treatment the number of reticulocytes were found to be 45. On day 20, the MCV was 94 fl and hemoglobin was 11.9 g/dl. The patient was administered 1 mg of vitamin B12 once a month during the first 3 years. His growth during these 3 years has been consistent with his age and his hematological values within normal ranges. A clinical check up consisting of hemogram and urinary tests on his parents and his two siblings, who were 8 and 10 years old, yielded normal results. Discussion The clinical presentation of IGS and nutritional Vitamin B12 deficiency are quite similar, because IGS results also from Vitamin B12 deficiency. However, in IGS Vitamin B12 deficiency arises as a result of problems with Vitamin B12 in intestine which cause insufficient Vitamin B12 absorption. Therefore, it's crucial to make the differntial diagnosis since the treatment of both is different. Uptake of Vitamin B12 (cyanocobalamin) is facilitated by the cobalamin-binder gastric intrinsic factor (IF), which recognizes a 460-kD receptor, cubilin, that is present in the epithelium of intestine and kidney(3). The human cubilin gene was mapped on the short arm of chromosome 10(3). The impaired synthesis, processing or ligand binding of cubilin is the molecular background of this heredi- tary form of megaloblastic anemia. The main test for differential diagnosis is abnormal Schilling test results. In our case, this test was abnormal. IGS has been reported to be of autosomal recessive inheritance and has definite epidemio-logical and geographical distribution. One sister of the index case frequently had infections and she died of complications due to anemia. Her death may have been due to a missed diagnosis of IGS. Proteinuria accompanies this syndrome in 70% of the cases. The pathogenesis of protein-uria has yet to be understood. However, we didn't detect proteinuria in this case. Since Vitamin B12 takes part in myelin synthesis neu-rological symptoms may accompany IGS(6). We didn't observe any neurologic symptoms in this case. The diagnosis of IGS was based on marked macrocytic anemia, very low serum Vitamin B12 levels and abnormal Schilling urinary excretion levels. This case illustrates that in megaloblastic anemia in infancy, the investigation should include a search for IGS as well as nutritional Vitamin B12 deficiency. References 1. Imerslund O. Idiopatik megaloblastic anemia in children. Acta Pediatr 1960; 119 (Suppl): 1-115. 2. Grasbeck R, Gordion R, Kantero I, Kuhlback B. Selective vitamin B12 malabsorption in young people: A syndrome. Acta Med Scan 1960; 167: 289-296. 3. Kozyraki R, Kristiansen M, silahtaroglu A, Hansen C, Jacobsen C, Tommerup N, et al. The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromo-somal mapping of the gene to 10p within the autosomal recessive megaloblatic anemia (MGA1) region. Blood 1998; 91: 3593-3600. 4. Sayli RT, Basak NA, Gumruk F, Gurgey A, Altay C. Imerslund-Grasbeck syndrome coexisting with b-thalassemia trait. Pediatr Hematol Oncol 1994; 11: 223-225. 5. Abdelaal MA, Ahmed AF. Imerslund-Grasbeck Syndrome in a Saudi Family. Acta Pediatr Scand 1991; 80: 1109-1112. 6. Lanzkowsky P. Megaloblastic anemia. in: Hematology and Oncology. Ed. Lanzkowsky P. New York, Churchill Livinstone, 1995; pp 51-61. |
