Familial Selective Vitamin B₁₂Malabsorption (Imerslund-Grasbeck Syndrome) in a Pool of Turkish Patients

Abstract

Thirty-six patients with Imerslund-Gräsbeck syndrome are presented. The mean ages at presentation and diagnosis were 4.7 +/- 3.7 years and 7.2 +/- 4.2 years, respectively. The mean hemoglobin level was 5.8 +/- 2.2 g/dL, the mean cell volume was 104.9 +/- 11.6 fL, the white blood cell count was 4479 +/- 2022/mm3, and the serum vitamin B12 level was 96.9 +/- 73 pg/mL. At diagnosis, 5 of the 36 patients, aged 5 to 16 years, had neurologic symptoms. All the patients had severe megaloblastic changes in bone marrow precursor cells. Proteinuria was detected in 78% of them. Patients with proteinuria had a younger age of onset (P < 0.0001) and diagnosis (P < 0.001) compared with those without proteinuria. In all patients, vitamin B12 excretion unbound to intrinsic factor after a flushing dose of vitamin B12 was lower than normal, and there was no appreciable correction in urinary vitamin B12 excretion after binding of intrinsic factor. The impairment of vitamin B12 absorption studies in Schilling tests; however, showed great variation among patients. Serum haptoglobin values were close to zero in all patients, indicating the presence of that intravascular hemolysis in Imerslund-Gräsbeck syndrome. Variations among patients in the age of presentation, degree of impairment of vitamin B12 absorption, and presence or absence of proteinuria suggest a heterogeneity in etiology of Imerslund-Gräsbeck syndrome at the molecular level.

Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7

“…Mild proteinuria is not always present in Imerslund-Gräsbeck disease and patients without proteinuria have a tendency to present cobalamin deficiency symptoms later in life. 17 Up till now, most reported IGS cases were caused by a CUBN founder mutation in Finland and by a founder AMN mutation in Norway, whereas in Middle Eastern countries, mutations were identified on both genes. 7,10,17 In a previous case with English-Israeli parentage and AMN compound mutations, the first mutation was expected to truncate the protein and the second (c.701G>T, C234F) to alter the residual function of cubam.…”

“…17 Up till now, most reported IGS cases were caused by a CUBN founder mutation in Finland and by a founder AMN mutation in Norway, whereas in Middle Eastern countries, mutations were identified on both genes. 7,10,17 In a previous case with English-Israeli parentage and AMN compound mutations, the first mutation was expected to truncate the protein and the second (c.701G>T, C234F) to alter the residual function of cubam. 18 It has been suggested that AMN is a 'moonlighting' protein that fulfils 2 functions, one in embryonic development, proved in mice and the other in Cbl absorption, demonstrated in humans.…”

Genetic heterogeneity of megaloblastic anaemia type 1 in Tunisian patients

“…Patients have decreased levels of serum Vit B12 in the presence of normal levels of intrinsic factor (IF) (Mackenzie et al 1972;Burman et al 1985). Classically, patients present during childhood with pallor, developmental delays and variable neurological symptoms (Campbell et al 1981;Broch et al 1984;Salameh et al 1991;Wulffraat et al 1994;Altay et al 1995;Carmel et al 2003). The therapy consists of periodic parenteral administration of Vit B12 that restores normal metabolism and haematopoiesis.…”

“…The disease is also frequent in several Middle Eastern countries, including Turkey, Kuwait, Saudi Arabia and Israel (Ben-Bassat et al 1969;Yetgin et al 1983;Abdelaal and Ahmed 1991;Salameh et al 1991;Altay et al 1995;Celep et al 1996;Ismail et al 1997;Tanner et al 2004). In Tunisia, 24 cases have been diagnosed, but only some have been published (el Bez et al 1992;Ben Meriem et al 1993;Fitouri et al 2001).…”

Nonradioactive Vitamin B12 Absorption Test Evaluated in Controls and in Patients with Inherited Malabsorption of Vitamin B12

“…An alternative approach is therefore needed for estimation of the absorption of vitamin B 12 . Measurement of vitamin B 12 -saturated transcobalamin (holo-TC) 4 or total cobalamin after oral ingestion of vitamin B 12 may represent such a test.…”