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PubMed This is a summary of 9 peer-reviewed journal articles Updated
Dermatology

Symptoms and Triggers: What to Watch For

At a Glance

Hartnup disease is an episodic condition that can cause sun-sensitive skin rashes, poor muscle coordination, and sudden mood changes. Flare-ups are typically triggered by sunlight exposure, illness, a lack of dietary protein, or certain medications that deplete tryptophan and niacin levels.

Hartnup disease is often called an “episodic” condition because symptoms can come and go, frequently triggered by external factors [1][2]. While many people with the genetic markers for Hartnup disease remain completely asymptomatic (showing no symptoms at all), others experience a range of physical and mental changes when their body’s supply of tryptophan and niacin becomes too low [3][4].

Dermatological: The “Pellagra-Like” Rash

The most recognizable sign of Hartnup disease is a skin rash that mimics pellagra (a severe niacin deficiency) [5][6].

  • Photosensitivity: The rash is photosensitive, meaning it is triggered or worsened by exposure to ultraviolet (UV) light from the sun [5][2].
  • Appearance: It typically appears on sun-exposed areas like the face, neck, and hands. It often looks red and scaly (erythematous) and can sometimes resemble eczema [5][6].
  • Flare-ups: These skin issues often appear during the summer months or after a significant increase in sun exposure [5].

Gastrointestinal: The Hidden “D” of Pellagra

Because Hartnup disease shares features with pellagra, patients may also experience the classic “3 Ds” of niacin deficiency (Dermatitis, Diarrhea, and Dementia) [5][1].

  • Diarrhea and Discomfort: During a flare-up, a patient may develop diarrhea, vague abdominal pain, or poor appetite [5].
  • Glossitis: Some patients may experience a red, swollen, or sore tongue (glossitis) which can make eating uncomfortable [5].

Neurological: Coordination and Movement

When the body lacks the building blocks it needs, the nervous system can be affected. These symptoms can be frightening but are often reversible with proper treatment [6][2].

  • Ataxia: This is the most common neurological symptom, appearing as an unsteady gait or a lack of muscle coordination that can make walking or fine motor tasks difficult [1][2].
  • Tremors and Spasticity: Some patients may experience involuntary shaking (tremors) or muscle stiffness and tightness (spasticity) [2][6].
  • Encephalopathy: In rare or severe cases, a person might experience intermittent encephalopathy, which is a general term for altered brain function that can cause confusion or lethargy [4][6].

Neuropsychiatric: Mood and Behavior

The brain relies on tryptophan to produce serotonin, which regulates mood. A deficiency can lead to a variety of emotional and behavioral changes [7][6].

  • Mood Changes: Patients may experience periods of anxiety, depression, or sudden irritability [7][6].
  • Behavioral Problems: Some children may show signs of impulsivity or other behavioral challenges during a flare-up [6].

Common Triggers for Symptoms

Symptoms usually do not appear out of nowhere; they are often “pulled out” by specific triggers that increase the body’s demand for niacin or decrease its supply [1][5].

  • Sunlight: Direct exposure to UV rays is a primary trigger for skin symptoms [5].
  • Poor Diet: A lack of dietary protein (which provides tryptophan) can cause symptoms to emerge [6][2].
  • Illness and Fever: Times of infection or high fever put extra stress on the body’s metabolism, which can trigger an episode [1][2].
  • Medications: Certain medications, such as those used to treat tuberculosis (like isoniazid), can interfere with niacin levels and may trigger symptoms [8][9].

Return to the Home Page or read about The Biology and Genetics of Hartnup Disease.

Common questions in this guide

What are the main symptoms of a Hartnup disease flare-up?
The most recognizable sign is a red, scaly skin rash that mimics pellagra and appears on sun-exposed areas like the face, neck, and hands. Other common symptoms include an unsteady walk, diarrhea, and sudden changes in mood or behavior.
What causes Hartnup disease symptoms to start?
Flare-ups are generally triggered by external stressors that increase the body's demand for niacin. Common triggers include direct exposure to ultraviolet (UV) sunlight, illnesses with high fevers, a diet low in protein, or certain medications.
Does sunlight make Hartnup disease worse?
Yes, sunlight is a primary trigger for the dermatological symptoms of Hartnup disease. Exposure to ultraviolet (UV) rays can cause or worsen a red, scaly skin rash on exposed areas, often leading to flare-ups during the summer months.
Can Hartnup disease cause mental health or behavior changes?
Yes, a deficiency in tryptophan can disrupt serotonin production, which regulates mood. During a flare-up, patients may experience anxiety, depression, sudden irritability, or behavioral challenges such as impulsivity.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Are my child's current symptoms typical for an acute flare-up of Hartnup disease?
  2. 2.What specific SPF rating and type of sunscreen do you recommend for daily recess and outdoor play?
  3. 3.How can we distinguish between a normal mood swing and a neuropsychiatric symptom of the disease?
  4. 4.Should we adjust the protein or niacin intake during times of illness or high stress?
  5. 5.Are there any specific medications, like isoniazid, that we must avoid to prevent triggering symptoms?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (9)
  1. 1

    New aspects for the brain in Hartnup disease based on mining of high-resolution cellular mRNA expression data for SLC6A19.

    Kravetz Z, Schmidt-Kastner R

    IBRO neuroscience reports 2023; (14()):393-397 doi:10.1016/j.ibneur.2023.03.010.

    PMID: 37101820
  2. 2

    Hartnup disease presenting as hereditary spastic paraplegia and severe peripheral neuropathy.

    Wang X, Li XY, Piao Y, et al.

    American journal of medical genetics. Part A 2022; (188(1)):237-242 doi:10.1002/ajmg.a.62475.

    PMID: 34459558
  3. 3

    Excretion of excess nitrogen and increased survival by loss of SLC6A19 in a mouse model of ornithine transcarbamylase deficiency.

    Belanger AJ, Gefteas E, Przybylska M, et al.

    Journal of inherited metabolic disease 2023; (46(1)):55-65 doi:10.1002/jimd.12568.

    PMID: 36220785
  4. 4

    Study of Seizure-Manifested Hartnup Disorder Case Induced By Novel Mutations in SLC6A19.

    Zhu Y, Chen L, He J, et al.

    Open life sciences 2018; (13()):22-27 doi:10.1515/biol-2018-0003.

    PMID: 33817063
  5. 5

    ACE2 and gut amino acid transport.

    Camargo SMR, Vuille-Dit-Bille RN, Meier CF, Verrey F

    Clinical science (London, England : 1979) 2020; (134(21)):2823-2833 doi:10.1042/CS20200477.

    PMID: 33140827
  6. 6

    Adult Neuropsychiatric Manifestation of Hartnup Disease With a Novel SLCA6A19 Variant: A Case Report.

    Bachmann T, Faust H, Abou Jamra R, et al.

    Neurology. Genetics 2024; (10(6)):e200195 doi:10.1212/NXG.0000000000200195.

    PMID: 39611136
  7. 7

    Loss of CLTRN function produces a neuropsychiatric disorder and a biochemical phenotype that mimics Hartnup disease.

    Pillai NR, Yubero D, Shayota BJ, et al.

    American journal of medical genetics. Part A 2019; (179(12)):2459-2468 doi:10.1002/ajmg.a.61357.

    PMID: 31520464
  8. 8

    Protective effect of Bifidobacterium longum BB536 against nausea caused by pirfenidone in a mouse model of pellagra.

    Kuronuma K, Susai N, Kuroita T, et al.

    Bioscience of microbiota, food and health 2023; (42(3)):195-202 doi:10.12938/bmfh.2022-042.

    PMID: 37404569
  9. 9

    Analysis of real-world data and a mouse model indicates that pirfenidone causes pellagra.

    Kuronuma K, Susai N, Kuroita T, et al.

    ERJ open research 2022; (8(4)) doi:10.1183/23120541.00245-2022.

    PMID: 36299372

This page provides educational information about the symptoms and triggers of Hartnup disease. It is not intended as medical advice; always consult your pediatrician or physician if you or your child experience concerning symptoms or skin changes.

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