Hereditary intrinsic factor deficiency in China caused by a novel mutation in the intrinsic factor gene—a case report

Background Hereditary intrinsic factor deficiency is a rare disease characterized by cobalamin deficiency with the lack of gastric intrinsic factor because of gastric intrinsic factor (GIF) mutations. Patients usually present with cobalamin deficiency without gastroscopy abnormality and intrinsic factor antibodies. Case presentation A Chinese patient presented with recurrent severe anemia since age 2 with low cobalamin level and a mild elevation of indirect bilirubin. The hemoglobin level normalized each time after intramuscular vitamin B12 injection. Gene test verified a c.776delA frame shift mutation in exon 6 combined with c.585C > A nonsense early termination mutation in exon 5 of GIF which result in the dysfunction of gastric intrinsic factor protein. The hereditary intrinsic factor deficiency in literature was further reviewed and the ancestry of different mutation sites were discussed. Conclusions A novel compound heterozygous mutation of GIF in a Chinese patient of hereditary intrinsic factor deficiency was reported. It was the first identified mutation of GIF in East-Asia and may indicate a new ancestry.

Autoimmune Gastritis

Context.— Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia. Autoimmune gastritis is a microscopic disease because patients present with no or vague symptoms, and clinicians rarely find endoscopic changes. Autoimmune gastritis only becomes a clinical disease when pathologists diagnose it in gastric biopsies performed for a variety of clinical indications. Unfamiliarity with this disease can result in misdiagnosis of patients, and thus inadequate patient management. Objective.— To review the pathogenesis, clinical features, diagnostic criteria, differential diagnoses, sequelae, and surveillance recommendations for AG. Data Sources.— The sources of the study include a review of the pertinent literature for AG. Conclusions.— Autoimmune gastritis is an important disease characterized by a loss of oxyntic mucosa and presence of metaplastic epithelium and enterochromaffin-like cell hyperplasia. Awareness and proper diagnosis are critical to prevent mismanagement of patients.

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

Background: Current tests for evaluation of vitamin B12 absorption are problematic because they involve the use of radioactively labeled vitamin B12. We describe a vitamin B12 absorption test that circumvents this problem.Methods: We measured cobalamin or transcobalamin saturated with cobalamin (holo-TC) 24 h after three 9-μg doses of vitamin B12 given orally at 6-h intervals. We studied 17 patients with inherited malabsorption of vitamin B12 attributable to Imerslund–Grasbeck syndrome (n = 13) or intrinsic factor deficiency (n = 4), their obligate heterozygous biological parents (n = 19), and healthy controls (n = 44).Results: In the patients, the median (range) change of holo-TC after the B12 load was not significant [1 (−42 to 5) pmol/L], nor was the change of cobalamin [−3 (−32 to 22) pmol/L], consistent with a lack of measurable active or passive absorption. In controls, however, the median (range) increases of holo-TC and cobalamin were 26 (−6 to 63) pmol/L and 41 (−37 to 109) pmol/L, respectively. Similarly, the parents showed increases of 23 (−2 to 47) pmol/L and 27 (−15 to 94) pmol/L. The mean areas under the ROC curves (95% confidence intervals) were 0.97 (0.93–1.0) for holo-TC and 0.87 (0.79–0.94) for cobalamin, distinguishing patients from controls. At a cutoff of 6 pmol/L for holo-TC, the diagnostic sensitivity (95% confidence interval) was 100 (81–100)%, and the diagnostic specificity was 92 (82–97)%.Conclusion: Measurement of holo-TC after administration of vitamin B12 is a promising approach for evaluating vitamin B12 absorption.

Identification of a 4-base deletion in the gene in inherited intrinsic factor deficiency

A 4-base deletion has been identified in the coding region of the gene for gastric intrinsic factor (IF) in an 11-year-old girl with severe anemia and cobalamin (Cbl) deficiency. The bone marrow showed frank megaloblastic morphology, and the Schilling test indicated a failure to absorb Cbl that was corrected by coadministration of IF. Pentagastrin administration induced acid secretion, but the gastric juice lacked IF as determined by CbI binding, by fractionation of protein-bound CbI, and by immunoprecipitation with anti-IF antiserum. Individual exons were amplified by the polymerase chain reaction by using primers to the flanking intronic regions, and the nucleotide sequence analysis identified a 4-base deletion (c183_186delGAAT) spanning positions 104 to 107 in exon 2, resulting in premature termination of translation. This mutation also eliminates a site for Bst XI endonuclease and introduces a site for BsaBI for identifying this deletion in hereditary IF deficiency.