hereditary intrinsic factor deficiency

Hereditary intrinsic factor deficiency is a rare inherited condition that disrupts the absorption of vitamin B12, leading to megaloblastic anemia and a range of neurological abnormalities. It results from mutations in the CBLIF gene, which is essential for the production of intrinsic factor, a key protein in vitamin B12 uptake. Most individuals present in childhood with symptoms related to anemia and subsequent neurological complications. In terms of prevalence, this disorder is very rare, affecting fewer than 1 in 1,000,000 people.

The clinical features of hereditary intrinsic factor deficiency are marked by consistent laboratory abnormalities. Patients invariably exhibit megaloblastic anemia, which is reflected by increased red blood cell distribution width, elevated lactate dehydrogenase, reduced haptoglobin levels, and , an absence of intrinsic factor. In addition, malabsorption of vitamin B12 and reduced circulating vitamin B12 concentrations are characteristic findings that lead to symptomatic anemia and fatigue. A subset of individuals, in approximately 30-79% of cases, may experience neurocognitive challenges such as specific learning disabilities, hyperhomocystinemia, and even dementia. Other features, including recurrent infections, headache, spinal cord atrophy, peripheral neuropathy, methylmalonic acidemia, and growth delay, occur less frequently. Not all individuals experience all features, and severity varies considerably.

Hereditary intrinsic factor deficiency is caused by pathogenic variants in the CBLIF gene, which plays a critical role in producing intrinsic factor necessary for vitamin B12 absorption. The disruption of this gene's normal function results in the inability to effectively absorb cobalamin, leading to megaloblastic anemia and related neurologic issues. This condition is inherited in an autosomal recessive pattern, meaning that an affected individual has inherited two copies of the mutated gene, one from each parent. Because autosomal recessive conditions are more common when parents share a common ancestor, carrier testing may be particularly relevant for families with shared ancestry.

Currently, management focuses on supportive care and symptom management because there are no FDA-approved or foundational therapies specifically available for hereditary intrinsic factor deficiency. The mainstay of treatment is vitamin B12 supplementation to help correct the megaloblastic anemia and alleviate neurologic symptoms. In addition, patients benefit from a multidisciplinary approach where specialists such as hematologists, neurologists, and nutritionists collaborate to tailor treatment to the individual’s needs. Regular surveillance is an essential component of long-term care, as ongoing monitoring helps detect complications early and ensures that management strategies remain effective. Patients should discuss all treatment options with their healthcare team, and genetic counseling is recommended to help families understand both the condition and its implications for family planning.

The outlook for individuals with hereditary intrinsic factor deficiency can vary considerably depending on symptom severity, age at diagnosis, and access to comprehensive care. Many patients manage their symptoms well through sustained vitamin B12 supplementation and a structured treatment plan guided by specialists. Although the condition poses ongoing challenges due to impaired vitamin B12 absorption, outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with genetic counselors and specialists familiar with this condition to better understand management strategies and to monitor for any emerging complications.

Clinical trials exploring new treatment approaches for hereditary intrinsic factor deficiency are currently underway. Although no investigational therapies have been formally approved, several trials are investigating methods to optimize vitamin B12 absorption and improve overall patient outcomes. Individuals interested in participating in or learning more about these studies can search ClinicalTrials.gov or speak with their healthcare providers about their eligibility.