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Hereditary folate malabsorption
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Hereditary folate malabsorption

Hereditary folate malabsorption is a rare disorder that prevents the body from absorbing essential B vitamins called folates, leading to severe health complications if left untreated.

Overview

Hereditary folate malabsorption is a disorder that interferes with the body's ability to use certain vitamins from food. During digestion, the body cannot take in (absorb) certain B vitamins called folates, which are important for cell growth, function, and blood cell formation.

Infants with this condition are born with normal folate levels due to placental transfer before birth. Signs and symptoms typically appear within the first few months of life as they become unable to use folates from food.

Symptoms

  • Feeding difficulties
  • Diarrhea
  • Oral mucositis (swelling or irritation on the inside of the mouth)
  • Failure to thrive (not gaining weight or growing at the expected rate)
  • Megaloblastic anemia (a condition characterized by a low number of red blood cells that are larger than normal)
  • Leukopenia (fewer white blood cells, increasing susceptibility to infections)
  • Thrombocytopenia (fewer platelets, leading to easy bruising)

Without treatment, individuals may develop neurological problems, including developmental delays, intellectual disabilities, seizures, and ataxia (difficulty coordinating movements). Abnormal deposits of calcium (calcification) in the brain may also occur.

Pregnant women with this condition who receive treatment for the vitamin deficiency do not appear to have an increased risk of having children with birth defects caused by folate deficiency, such as spina bifida or anencephaly.

Frequency

The prevalence of hereditary folate malabsorption is unknown, with about 60 affected individuals reported worldwide. Researchers believe the disorder may be underdiagnosed in areas where advanced medical care is not available.

Causes

Hereditary folate malabsorption is caused by variants in the SLC46A1 gene. This gene provides instructions for making a protein called the proton-coupled folate transporter (PCFT). This protein is found in the membrane of cells, primarily in the small intestine, where it helps transport folate into the cell. PCFT is also found in the brain, where it is involved in transporting folates between the brain and the surrounding fluid.

Variants in the SLC46A1 gene result in a PCFT protein that has little or no activity. Without functional PCFT, cells in the small intestine cannot absorb folates from food, and cells in the brain cannot transport folate to the cerebrospinal fluid.

Gene Associated with Hereditary Folate Malabsorption

  • SLC46A1

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell must have a variant to cause the disorder. Parents of an affected individual each carry one copy of the altered gene but typically do not show signs or symptoms.

Other Names for This Condition

  • Congenital defect of folate absorption
  • Congenital folate malabsorption
  • Folic acid transport defect

Frequently Asked Questions

Diagnosis usually starts with a complete blood count showing megaloblastic anemia, low serum folate, and elevated homocysteine. Confirmation is obtained by genetic testing for pathogenic variants in the SLC46A1 gene. Some centers also perform a folate absorption test using oral versus intravenous folate to demonstrate impaired uptake.
The mainstay of therapy is high‑dose oral or intravenous folinic acid (5‑10 mg/kg/day divided 2–3 times). Dosing is individualized based on age, weight, and serum folate levels, with regular monitoring every 1–3 months. Intravenous administration is used initially if the child cannot tolerate oral intake or has severe anemia.
New or worsening neurological symptoms such as seizures, ataxia, developmental regression, or irritability are red‑flags and require urgent evaluation. Sudden drops in hemoglobin, platelets, or white blood cells, or signs of infection (fever, oral ulcers) also merit prompt care.
During pregnancy and the first few weeks of life the infant receives folate via the placenta and breast milk, which may temporarily maintain normal levels. However, breast milk folate is insufficient once intestinal absorption fails, so treatment with folinic acid should be initiated as soon as the diagnosis is suspected, typically within the first month of life.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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