Congenital intrinsic factor deficiency

Congenital intrinsic factor deficiency (also known as hereditary intrinsic factor deficiency or congenital pernicious anemia) is a rare inherited disorder characterized by the absence or dysfunction of gastric intrinsic factor (IF), a glycoprotein produced by parietal cells of the stomach that is essential for the absorption of vitamin B12 (cobalamin) in the terminal ileum. Without functional intrinsic factor, vitamin B12 cannot be adequately absorbed, leading to severe vitamin B12 deficiency despite normal dietary intake. The disease primarily affects the hematologic and nervous systems. Patients typically present in early childhood, usually between the ages of 1 and 5 years, with megaloblastic anemia — characterized by fatigue, pallor, weakness, failure to thrive, and irritability. Neurological manifestations may develop if the condition is left untreated and can include developmental delay, hypotonia, peripheral neuropathy, and subacute combined degeneration of the spinal cord. Unlike autoimmune pernicious anemia seen in adults, congenital intrinsic factor deficiency is not associated with gastric atrophy or anti-intrinsic factor antibodies, and gastric acid secretion remains normal. The condition is caused by pathogenic variants in the GIF gene (encoding gastric intrinsic factor) and follows an autosomal recessive inheritance pattern. Diagnosis is established through laboratory findings of low serum vitamin B12, megaloblastic anemia, normal gastric histology, and absence of anti-intrinsic factor or anti-parietal cell antibodies, confirmed by molecular genetic testing. Treatment consists of lifelong parenteral (intramuscular) vitamin B12 injections, which effectively correct the anemia and prevent neurological complications. With early diagnosis and consistent treatment, patients can expect a normal quality of life.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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