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Hartnup disease

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Description

Hartnup disease is a condition caused by the body's inability to absorb certain protein building blocks (amino acids) from the diet. As a result, affected individuals are not able to use these amino acids to produce other substances, such as vitamins and proteins. Most people with Hartnup disease are able to get the vitamins and other substances they need with a well-balanced diet.

People with Hartnup disease have high levels of various amino acids in their urine (aminoaciduria). For most affected individuals, this is the only sign of the condition. However, some people with Hartnup disease have episodes during which they exhibit other signs, which can include skin rashes; difficulty coordinating movements (cerebellar ataxia); and psychiatric symptoms, such as depression or psychosis. These episodes are typically temporary and are often triggered by illness, stress, nutrient-poor diet, or fever. These features tend to go away once the trigger is remedied, although the aminoaciduria remains. In affected individuals, signs and symptoms most commonly occur in childhood.

Frequency

Hartnup disease is estimated to affect 1 in 30,000 individuals.

Causes

Hartnup disease is caused by mutations in the SLC6A19 gene. This gene provides instructions for making a protein called B0AT1, which is primarily found embedded in the membrane of intestine and kidney cells. The function of this protein is to transport certain amino acids into cells. In the intestines, amino acids from food are transported into intestinal cells then released into the bloodstream so the body can use them. In the kidneys, amino acids are reabsorbed into the bloodstream instead of being removed from the body in urine. In the body, these amino acids are used in the production of many other substances, including vitamins and proteins. One particular amino acid transported by B0AT1, tryptophan, is needed to produce vitamin B3 (also known as niacin).

SLC6A19 gene mutations result in the production of a B0AT1 protein with reduced activity. As a result, specific amino acids cannot be taken in by cells and are instead removed from the body as waste. Because these amino acids are removed from the body without being used, people with this condition may be lacking (deficient) in certain amino acids and vitamins. However, individuals who are nutrient-deficient due to their diet, illness, stress, or a variety of other reasons, can develop serious signs and symptoms of this condition including rashes, cerebellar ataxia, and psychiatric symptoms. Researchers believe that many of these features are related to a deficiency of tryptophan and niacin, specifically.

Inheritance

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.

Other Names for This Condition

  • Hartnup disorder
  • Hartnup's disease
  • neutral amino acid transport defect

Additional Information & Resources

Genetic and Rare Diseases Information Center

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Azmanov DN, Kowalczuk S, Rodgers H, Auray-Blais C, Giguère R, Rasko JE, Bröer S, Cavanaugh JA. Further evidence for allelic heterogeneity in Hartnup disorder. Hum Mutat. 2008 Oct;29(10):1217-21. doi: 10.1002/humu.20777. Citation on PubMed
  • Azmanov DN, Rodgers H, Auray-Blais C, Giguère R, Bailey C, Bröer S, Rasko JE, Cavanaugh JA. Persistence of the common Hartnup disease D173N allele in populations of European origin. Ann Hum Genet. 2007 Nov;71(Pt 6):755-61. Epub 2007 Jun 7. Citation on PubMed
  • Bröer S. The role of the neutral amino acid transporter B0AT1 (SLC6A19) in Hartnup disorder and protein nutrition. IUBMB Life. 2009 Jun;61(6):591-9. doi: 10.1002/iub.210. Review. Citation on PubMed
  • Camargo SM, Singer D, Makrides V, Huggel K, Pos KM, Wagner CA, Kuba K, Danilczyk U, Skovby F, Kleta R, Penninger JM, Verrey F. Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. Gastroenterology. 2009 Mar;136(3):872-82. doi: 10.1053/j.gastro.2008.10.055. Epub 2008 Oct 29. Citation on PubMed
  • Kleta R, Romeo E, Ristic Z, Ohura T, Stuart C, Arcos-Burgos M, Dave MH, Wagner CA, Camargo SR, Inoue S, Matsuura N, Helip-Wooley A, Bockenhauer D, Warth R, Bernardini I, Visser G, Eggermann T, Lee P, Chairoungdua A, Jutabha P, Babu E, Nilwarangkoon S, Anzai N, Kanai Y, Verrey F, Gahl WA, Koizumi A. Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder. Nat Genet. 2004 Sep;36(9):999-1002. Epub 2004 Aug 1. Citation on PubMed
  • Seow HF, Bröer S, Bröer A, Bailey CG, Potter SJ, Cavanaugh JA, Rasko JE. Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. Nat Genet. 2004 Sep;36(9):1003-7. Epub 2004 Aug 1. Citation on PubMed
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