Nutrition Diet and Understanding What is the Defect in Hartnup Disease?

November 7, 2025 •

5 min read

Affecting approximately 1 in 30,000 people, a genetic defect is what is the defect in Hartnup disease, a rare metabolic disorder that hinders the body's ability to absorb neutral amino acids. This defect can lead to nutritional deficiencies and a range of clinical symptoms if not managed with a specialized nutrition diet.

Quick Summary

Hartnup disease is an inherited disorder caused by a mutation in the SLC6A19 gene, resulting in a defective transport protein that causes poor intestinal absorption and excessive renal loss of neutral amino acids. This leads to deficiencies, most notably a lack of niacin, causing various cutaneous and neurological symptoms.

Key Points

Genetic Defect: Hartnup disease is caused by mutations in the SLC6A19 gene, affecting the B0AT1 neutral amino acid transporter.
Impaired Transport: The defect leads to malabsorption of neutral amino acids in the intestines and their excessive loss through the kidneys.
Niacin Deficiency: The malabsorption of tryptophan, a precursor for niacin (vitamin B3), often results in a deficiency of this essential vitamin.
Triggered Symptoms: Clinical episodes, including skin rashes and neurological issues, are frequently triggered by poor nutrition, stress, or sun exposure.
Dietary Management: A high-protein diet is a primary treatment to compensate for amino acid loss.
Niacin Supplementation: Niacin or niacinamide supplements can alleviate symptoms related to the niacin deficiency.
Peptide Absorption: The body can still absorb di- and tripeptides, allowing for the use of protein hydrolysate supplements if necessary.
Asymptomatic Cases: Many individuals with Hartnup disease never experience symptoms if their nutritional intake is adequate.

Hartnup disease is a rare, inherited metabolic disorder that affects the body's ability to absorb and reabsorb neutral amino acids from the diet. While many individuals with this genetic condition remain asymptomatic, nutritional deficiencies or periods of high stress can trigger clinical episodes with severe consequences. Understanding the specific defect and its impact on nutrition is crucial for effective management through a targeted diet.

The Genetic Basis: What is the Defect in Hartnup Disease?

The root cause of Hartnup disease lies in a genetic mutation. The condition is inherited in an autosomal recessive pattern, meaning an affected individual inherits a mutated copy of a specific gene from each parent. This key defect involves the SLC6A19 gene, which provides instructions for making the neutral amino acid transporter known as B0AT1.

Gene: SLC6A19, located on chromosome 5.
Protein: B0AT1, a sodium-dependent transporter.

This defective B0AT1 protein fails to function correctly in two critical locations: the small intestine and the proximal tubules of the kidneys. This dual-location defect creates a two-pronged problem for the body's amino acid balance.

The Defective Transport Mechanism

The non-functional B0AT1 protein impairs the body's transport system in two ways:

Intestinal Malabsorption: In the small intestine, the B0AT1 transporter normally helps absorb neutral amino acids from digested food and move them into the bloodstream. In Hartnup disease, this process is impaired, causing many amino acids to pass through the digestive system unabsorbed.
Renal Wasting: In the kidneys, the transporter reabsorbs amino acids from the filtered blood back into the body. The defective transporter leads to a failure in this reabsorption process, causing an excessive loss of neutral amino acids in the urine, a condition known as aminoaciduria.

This inefficient transport system leads to a systemic deficiency of several neutral amino acids, with tryptophan being of particular clinical importance due to its role in producing vital compounds.

Nutritional Consequences of the Defect

The impaired absorption and excessive loss of neutral amino acids, especially tryptophan, result in significant nutritional fallout. The body is unable to acquire sufficient amounts of these protein building blocks, which are used to produce other substances, including vitamins and proteins.

Niacin Deficiency: Tryptophan is an essential amino acid and a key precursor for the synthesis of niacin (vitamin B3). With inadequate tryptophan absorption, the body's ability to produce niacin is compromised, leading to symptoms that mimic pellagra, a condition caused by dietary niacin deficiency.
Reduced Serotonin Synthesis: Tryptophan is also a precursor for the neurotransmitter serotonin. Low levels of tryptophan can disrupt serotonin synthesis, which may contribute to the neurological and psychiatric symptoms seen in some patients.
Gut Bacterial Metabolism: The unabsorbed amino acids accumulate in the large intestine where they are metabolized by gut bacteria. Some by-products of this process, such as indolic compounds, are absorbed and may be toxic to the nervous system, potentially exacerbating neurological symptoms.

Managing Hartnup Disease with a Specialized Diet

Dietary management is the cornerstone of preventing and treating the symptoms of Hartnup disease. By maintaining adequate nutrition, particularly with a high-protein diet, many individuals can remain asymptomatic. A high-protein diet increases the pool of available amino acids, compensating for the transport defect.

Key Dietary and Supplementation Strategies

High-Protein Diet: Increasing protein intake ensures a higher concentration of amino acids, allowing the body to absorb enough despite the transporter deficiency. This is especially important during periods of illness or stress, which can trigger symptomatic episodes.
Niacin/Niacinamide Supplements: Supplementation with niacin or niacinamide (a form of vitamin B3) is a crucial intervention, especially for symptomatic patients. Daily doses can reduce the number and severity of attacks by addressing the underlying niacin deficiency.
Dietary Sources of Niacin: Including foods naturally rich in niacin can support overall health. These include lean red meat, poultry, fish, peanuts, and fortified grains.
Leveraging Di-/Tripeptide Absorption: Interestingly, the absorption of di- and tripeptides remains intact in Hartnup disease. Protein hydrolysates, which contain these smaller peptide chains, can be a beneficial dietary supplement.

Comparing Nutritional Management Strategies


Feature	High-Protein Diet	Niacin/Niacinamide Supplementation	Protein Hydrolysates
Mechanism	Increases the overall pool of amino acids to overcome malabsorption and wasting.	Directly addresses the deficiency of niacin, which is caused by the lack of tryptophan.	Provides amino acids in the form of di- and tripeptides, which are absorbed via a different, unaffected pathway.
Effectiveness	Highly effective for preventing symptomatic episodes in most patients, particularly those with a normal diet.	Proven to ameliorate skin eruptions and neurological symptoms during symptomatic attacks.	Can be beneficial for supplementing amino acid intake, especially for those who struggle with high-protein foods.
Application	Long-term, foundational dietary approach for daily management.	Used both for prevention and active treatment of symptomatic episodes.	Can be a complementary strategy, particularly in cases of severe nutritional deficiency or poor oral intake.

Common Triggers and Symptoms of Hartnup Episodes

Although the aminoaciduria is constant, the clinical symptoms of Hartnup disease are often intermittent and reversible. They are frequently triggered by factors that increase the body's nutritional demands or reduce amino acid availability.

Common Triggers:

Poor nutrition or low protein intake
Illness or fever
Physical or emotional stress
Sunlight exposure
Certain medications, including sulfonamides

Key Symptoms During Episodes:

Cutaneous Manifestations: A photosensitive, pellagra-like skin rash on sun-exposed areas.
Neurological Disturbances: This can include cerebellar ataxia (uncoordinated gait), tremors, and headaches.
Psychiatric Symptoms: Emotional lability, depression, delusions, and psychosis can occur.

Conclusion: Living with Hartnup Disease

Understanding what is the defect in Hartnup disease is the first step toward effective management and a normal life expectancy. The genetic mutation in the SLC6A19 gene leads to impaired neutral amino acid transport, causing deficiencies, particularly in niacin. However, most affected individuals can control their condition by maintaining a nutritious diet rich in protein, supplementing with niacin or niacinamide, and avoiding known triggers like excessive sun exposure. The prognosis for those with Hartnup disease who receive proper dietary and medical management is generally good, with the frequency and severity of episodes often diminishing with age. The ongoing study of this rare disorder continues to provide new insights into amino acid transport and its role in overall health.

For more detailed information on Hartnup disease, you can consult reliable sources such as the National Organization for Rare Disorders (NORD).

Frequently Asked Questions

The defect in Hartnup disease is a mutation in the SLC6A19 gene, which disrupts the function of the B0AT1 neutral amino acid transporter protein. This leads to impaired absorption of neutral amino acids in the intestines and their excessive excretion by the kidneys.

The defect prevents the body from properly absorbing certain amino acids, especially tryptophan, from food. This can lead to nutritional deficiencies, particularly a lack of niacin (vitamin B3), which must be managed with a high-protein diet and supplements.

Yes, with proper management, most individuals with Hartnup disease can lead healthy lives. Maintaining a good nutrition diet, taking supplements, and avoiding triggers are key to preventing symptomatic episodes.

The most common symptoms, which appear intermittently, include a photosensitive skin rash similar to pellagra, cerebellar ataxia (uncoordinated movements), headaches, and psychiatric issues like mood changes.

The amino acid tryptophan is a metabolic precursor for the synthesis of niacin. In Hartnup disease, the body's inability to properly absorb tryptophan leads to a secondary niacin deficiency, which is responsible for many of the clinical symptoms.

Symptomatic attacks are often precipitated by factors that increase nutritional demands or stress the body, such as periods of poor nutrition, fever, illness, emotional stress, and exposure to sunlight.

Pellagra is a condition caused by a dietary deficiency of niacin. Hartnup disease is a genetic disorder that causes a functional niacin deficiency due to impaired tryptophan absorption. The symptoms of Hartnup disease resemble pellagra but have a different underlying cause.