Isolation and characterization of an abnormal human intrinsic factor

Area of Science:

• Biochemistry
• Genetics
• Gastroenterology

Background:

• A patient presented with vitamin B12 deficiency due to a functionally abnormal intrinsic factor (IF).
• Intrinsic factor is crucial for vitamin B12 absorption in the ileum.

Purpose of the Study:

• To characterize the abnormal intrinsic factor (IF) in a patient with vitamin B12 deficiency.
• To determine the genetic basis and functional consequences of the abnormal IF.

Main Methods:

• Isolation of intrinsic factor (IF) from patient and family members using affinity chromatography.
• Assessing IF-B12 binding affinity and ileal receptor interaction in vitro.
• Performing Schilling tests with patient and family gastric juice to evaluate B12 absorption.

Main Results:

• Patient's IF showed normal binding to B12 but significantly reduced affinity for ileal receptors.
• Family members (mother, father, sister) exhibited intermediate IF-B12 binding and ileal receptor affinity.
• Schilling tests confirmed reduced B12 absorption with patient and family gastric juice compared to normal.

Conclusions:

• The patient is homozygous for a structurally abnormal IF, while parents and sister are heterozygous.
• The abnormal IF has a markedly decreased affinity for ileal vitamin B12 receptors.
• The findings suggest distinct molecular sites for B12 and ileal receptor binding on the IF molecule.