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Hereditary folate malabsorption

Reviewed May 2009

What is hereditary folate malabsorption?

Hereditary folate malabsorption is a disorder that interferes with the body's ability to absorb certain B vitamins (called folates) from food. Folates are important for many cell functions, including the production of DNA and its chemical cousin, RNA.

Infants with hereditary folate malabsorption are born with normal amounts of folates in their body because they obtain these vitamins from their mother's blood before birth. They generally begin to show signs and symptoms of the disorder within the first few months of life because their ability to absorb folates from food is impaired.

Infants with hereditary folate malabsorption experience feeding difficulties, diarrhea, and failure to gain weight and grow at the expected rate (failure to thrive). Affected individuals usually develop a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, and tingling or numbness in the hands and feet. People with hereditary folate malabsorption may also have a deficiency of white blood cells (leukopenia), leading to increased susceptibility to infections. In addition, they may have a reduction in the amount of platelets (thrombocytopenia), which can result in easy bruising and abnormal bleeding.

Some infants with hereditary folate malabsorption exhibit neurological problems such as developmental delay and seizures. Over time, untreated individuals may develop intellectual disability and difficulty coordinating movements (ataxia).

How common is hereditary folate malabsorption?

The prevalence of hereditary folate malabsorption is unknown. Approximately 15 affected families have been reported worldwide. Researchers believe that some infants with this disorder may not get diagnosed or treated, particularly in areas where advanced medical care is not available.

What genes are related to hereditary folate malabsorption?

The SLC46A1 gene provides instructions for making a protein called the proton-coupled folate transporter (PCFT). PCFT is important for normal functioning of intestinal epithelial cells, which are cells that line the walls of the intestine. These cells have fingerlike projections called microvilli that absorb nutrients from food as it passes through the intestine. Based on their appearance, groups of these microvilli are known collectively as the brush border. PCFT is involved in the process of using energy to move folates across the brush border membrane, a mechanism called active transport. It is also involved in the transport of folates between the brain and the fluid that surrounds it (cerebrospinal fluid).

Mutations in the SLC46A1 gene result in a PCFT protein that has little or no activity. In some cases the mutated protein is not transported to the cell membrane, and so it is unable to perform its function. A lack of functional PCFT impairs the body's ability to absorb folates from food, resulting in the signs and symptoms of hereditary folate malabsorption.

Related Gene(s)

Changes in this gene are associated with hereditary folate malabsorption.

  • SLC46A1

How do people inherit hereditary folate malabsorption?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of hereditary folate malabsorption?

These resources address the diagnosis or management of hereditary folate malabsorption and may include treatment providers.

  • Gene Review: Hereditary Folate Malabsorption (http://www.ncbi.nlm.nih.gov/books/NBK1673)
  • Genetic Testing Registry: Congenital defect of folate absorption (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0342705)
  • MedlinePlus Encyclopedia: Folate (http://www.nlm.nih.gov/medlineplus/ency/article/002408.htm)
  • MedlinePlus Encyclopedia: Folate Deficiency (http://www.nlm.nih.gov/medlineplus/ency/article/000354.htm)
  • MedlinePlus Encyclopedia: Folate-Deficiency Anemia (http://www.nlm.nih.gov/medlineplus/ency/article/000551.htm)
  • MedlinePlus Encyclopedia: Malabsorption (http://www.nlm.nih.gov/medlineplus/ency/article/000299.htm)

You might also find information on the diagnosis or management of hereditary folate malabsorption in Educational resources (http://www.ghr.nlm.nih.gov/condition/hereditary-folate-malabsorption/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/hereditary-folate-malabsorption/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about hereditary folate malabsorption?

You may find the following resources about hereditary folate malabsorption helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for hereditary folate malabsorption?

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

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about hereditary folate malabsorption?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding hereditary folate malabsorption?

anemia ; ataxia ; autosomal ; autosomal recessive ; brush border ; cell ; cell membrane ; congenital ; deficiency ; developmental delay ; disability ; DNA ; epithelial ; failure to thrive ; folate ; gene ; hereditary ; inherited ; intestine ; malabsorption ; megaloblastic anemia ; microvilli ; neurological ; platelets ; prevalence ; protein ; proton ; recessive ; RNA ; susceptibility ; thrombocytopenia ; vitamins ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Andrews NC. When is a heme transporter not a heme transporter? When it's a folate transporter. Cell Metab. 2007 Jan;5(1):5-6. (http://www.ncbi.nlm.nih.gov/pubmed/17189201?dopt=Abstract)
  • Gene Review: Hereditary Folate Malabsorption (http://www.ncbi.nlm.nih.gov/books/NBK1673)
  • Lasry I, Berman B, Straussberg R, Sofer Y, Bessler H, Sharkia M, Glaser F, Jansen G, Drori S, Assaraf YG. A novel loss-of-function mutation in the proton-coupled folate transporter from a patient with hereditary folate malabsorption reveals that Arg 113 is crucial for function. Blood. 2008 Sep 1;112(5):2055-61. doi: 10.1182/blood-2008-04-150276. Epub 2008 Jun 17. (http://www.ncbi.nlm.nih.gov/pubmed/18559978?dopt=Abstract)
  • Min SH, Oh SY, Karp GI, Poncz M, Zhao R, Goldman ID. The clinical course and genetic defect in the PCFT gene in a 27-year-old woman with hereditary folate malabsorption. J Pediatr. 2008 Sep;153(3):435-7. doi: 10.1016/j.jpeds.2008.04.009. (http://www.ncbi.nlm.nih.gov/pubmed/18718264?dopt=Abstract)
  • Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell. 2006 Dec 1;127(5):917-28. (http://www.ncbi.nlm.nih.gov/pubmed/17129779?dopt=Abstract)
  • Wolf G. Identification of proton-coupled high-affinity human intestinal folate transporter mutated in human hereditary familial folate malabsorption. Nutr Rev. 2007 Dec;65(12 Pt 1):554-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18236695?dopt=Abstract)
  • Zhao R, Matherly LH, Goldman ID. Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues. Expert Rev Mol Med. 2009 Jan 28;11:e4. doi: 10.1017/S1462399409000969. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19173758?dopt=Abstract)
  • Zhao R, Min SH, Qiu A, Sakaris A, Goldberg GL, Sandoval C, Malatack JJ, Rosenblatt DS, Goldman ID. The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption. Blood. 2007 Aug 15;110(4):1147-52. Epub 2007 Apr 19. (http://www.ncbi.nlm.nih.gov/pubmed/17446347?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2009
Published: December 22, 2014