How can I tell if my child’s rash is caused by Hartnup disease rather than a common skin condition?

Hartnup‑related rash typically appears as a symmetric, red‑brown, scaly eruption on sun‑exposed areas (face, neck, arms) and may worsen after a fever or illness. It often resembles pellagra‑type dermatitis and is accompanied by other signs such as ataxia or mood changes. A dermatologist can perform a skin biopsy, but the definitive clue is the presence of neutral aminoaciduria on urine testing.

What dietary changes can reduce the frequency of neurological episodes in Hartnup disease?

diet rich in protein (especially foods high in neutral amino acids like tryptophan) and fortified with niacin (vitamin B3) helps compensate for the absorption defect. Regular meals that include meat, dairy, legumes, and whole grains, plus a daily niacin supplement of 30‑50 mg, can lower the risk of rash, ataxia, and mood disturbances. Avoid prolonged fasting or very low‑protein diets, which can precipitate episodes.

Should I avoid any medications or supplements because they might worsen aminoaciduria?

Most common drugs do not affect the transport defect, but high‑dose vitamin B6 (pyridoxine) can increase urinary loss of neutral amino acids and should be used cautiously. Non‑steroidal anti‑inflammatory drugs (NSAIDs) and certain diuretics may increase renal excretion of amino acids, so discuss any new medication with your metabolic specialist.

How is Hartnup disease diagnosed and what tests are needed for family screening?

Diagnosis relies on a urine amino‑acid analysis showing markedly elevated neutral amino acids (especially tryptophan) with normal plasma levels. Genetic testing for pathogenic variants in SLC6A19 confirms the diagnosis. Once a pathogenic mutation is identified, targeted carrier testing or prenatal testing can be offered to siblings and future offspring.

Hartnup disease

Hartnup disease is an autosomal recessive disorder that impairs absorption of neutral amino acids, resulting in aminoaciduria and occasional skin, neurological, or psychiatric episodes.

Overview

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 experience episodes that can include skin rashes; difficulty coordinating movements; 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. The features tend to resolve once the trigger is remedied, although the aminoaciduria remains. Signs and symptoms most commonly occur in childhood.

Frequency

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

Causes & Risk Factors

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 intestinal and renal 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 instead of being removed from the body in urine. One particular amino acid transported by B0AT1, tryptophan, is needed to produce vitamin B3 (niacin).

SLC6A19 gene mutations result in a B0AT1 protein with reduced activity. Consequently, specific amino acids cannot be taken up by cells and are instead excreted in urine. Because these amino acids are removed without being used, individuals may become deficient in certain amino acids and vitamins, especially tryptophan and niacin, which is believed to underlie many of the skin and neuropsychiatric manifestations.

Gene involved

SLC6A19

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

Hartnup disorder
Hartnup's disease
Neutral amino acid transport defect

Additional Information & Resources

Genetic Testing Information

Genetic Testing Registry: Neutral 1 amino acid transport defect

Genetic and Rare Diseases Information Center

Hartnup disease

Patient Support and Advocacy Resources

National Organization for Rare Disorders (NORD)

Clinical Trials

ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

HARTNUP DISORDER; HND

Scientific Articles on PubMed

Azmanov DN, Kowalczuk S, Rodgers H, Auray-Blais C, Giguere R, Rasko JE, Broer S, Cavanaugh JA. Further evidence for allelic heterogeneity in Hartnup disorder. Hum Mutat. 2008 Oct;29(10):1217-21. doi: 10.1002/humu.20777.
Azmanov DN, Rodgers H, Auray-Blais C, Giguere R, Bailey C, Broer 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. doi: 10.1111/j.1469-1809.2007.00375.x.
Broer 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.
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.
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. doi: 10.1038/ng1405.
Seow HF, Broer S, Broer 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. doi: 10.1038/ng1406.

Medical Encyclopedia

Aminoaciduria
Genetics
Hartnup disorder

Understanding Genetics

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How can gene variants affect health and development?
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What are the different ways a genetic condition can be inherited?
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