Which Vitamin is Deficient in Hartnup Disease?

January 7, 2026 •

4 min read

Hartnup disease is a rare inherited disorder of amino acid metabolism that directly impacts the body's nutrient processing, which answers the question: which vitamin is deficient in Hartnup disease? The condition is caused by a genetic defect that impairs the absorption and reabsorption of neutral amino acids, especially tryptophan.

Quick Summary

Hartnup disease is a genetic disorder affecting tryptophan absorption, hindering the body's synthesis of niacin, also known as vitamin B3. This defect can lead to pellagra-like symptoms.

Key Points

Niacin (Vitamin B3) Deficiency: Hartnup disease leads to a deficiency of vitamin B3, specifically niacin, because the body cannot effectively absorb its amino acid precursor, tryptophan.
Genetic Defect: The core issue is a mutation in the SLC6A19 gene, which affects a transporter protein responsible for moving neutral amino acids across intestinal and kidney cell membranes.
Tryptophan Malabsorption: The defect causes impaired absorption of tryptophan from the small intestine and its increased excretion by the kidneys, reducing the body's supply.
Pellagra-like Symptoms: The resulting niacin deficiency causes symptoms similar to pellagra, including a photosensitive skin rash (dermatitis), neurological problems (ataxia), and mood changes.
Symptom Triggers: Attacks are often precipitated by factors that increase nutrient demand or reduce nutrient intake, such as poor nutrition, illness, or sun exposure.
Management: Treatment involves a high-protein diet to provide alternate sources of amino acids and supplementing with niacin or niacinamide to prevent symptoms.

Understanding the Genetic Basis of Hartnup Disease

Hartnup disease is a rare autosomal recessive metabolic disorder, meaning an individual must inherit a copy of the mutated gene from each parent to be affected. The root cause lies in a defective gene known as SLC6A19, located on chromosome 5. This gene provides instructions for creating a specific amino acid transporter protein, B0AT1, that is crucial for the absorption and reabsorption of neutral amino acids in the small intestine and kidneys.

When this transporter protein is faulty, neutral amino acids—including tryptophan, phenylalanine, and methionine—are not properly absorbed from the gut into the bloodstream. Instead, they pass through and are excreted, while those in the kidneys are not properly reabsorbed and are also lost in the urine. This defective transport is the central problem that triggers a cascade of nutritional consequences.

The Critical Link to Vitamin B3 (Niacin)

The connection between Hartnup disease and vitamin deficiency is directly related to the malabsorption of tryptophan. Tryptophan is not just an amino acid; it serves as a critical precursor for the body's synthesis of nicotinamide (niacinamide), a form of vitamin B3. While niacin can also be obtained from the diet, the body's ability to produce its own supply from tryptophan is vital, particularly during times of stress or inadequate protein intake.

Because the SLC6A19 gene mutation significantly reduces the amount of tryptophan available to the body, the internal production of niacin becomes severely impaired. It is this secondary, but critical, deficiency of vitamin B3 (niacin) that causes the hallmark pellagra-like symptoms observed in patients with Hartnup disease. The condition essentially mimics the effects of dietary niacin deficiency, but its origins are genetic rather than solely nutritional.

Symptoms Resembling Pellagra

The signs and symptoms of Hartnup disease are essentially those of pellagra, the classic niacin deficiency disease. These symptoms are often intermittent and triggered by factors such as sunlight exposure, fever, psychological stress, and poor nutrition. The characteristic features are sometimes referred to as the “three D's” of pellagra:

Dermatitis: A scaly, red skin rash appears on areas of the body exposed to sunlight, resembling a sunburn. The pattern can be distinct, such as Casal's necklace around the neck.
Diarrhea: Gastrointestinal distress and digestive issues can occur due to niacin's role in maintaining the health of the digestive tract.
Dementia and other neurological issues: Niacin is essential for nervous system function. Deficiency can lead to a variety of neurological and psychiatric symptoms, including ataxia (unsteady gait), mood changes, psychosis, and intellectual disability.

Diagnosis, Management, and Prognosis

Diagnosis

Diagnosing Hartnup disease typically involves a urine analysis to detect the excessive excretion of neutral amino acids, a condition known as neutral aminoaciduria. This test provides a definitive diagnosis by confirming the presence of the defective amino acid transport. It also helps differentiate it from other generalized aminoacidurias.

Management

Managing the condition focuses on preventing symptomatic episodes by ensuring adequate nutrient levels and avoiding triggers. The main strategies include:

High-Protein Diet: Consuming a diet rich in protein provides more raw material for nutrient absorption via peptide transport, a pathway that is unaffected by Hartnup disease. This can help offset the loss of amino acids.
Niacin Supplementation: Supplementing with niacin or niacinamide is crucial for preventing and treating symptomatic attacks. The dosage can be adjusted based on the severity of symptoms.
Trigger Avoidance: Patients are advised to minimize sun exposure, wear protective clothing, and use sunscreen to prevent the photosensitive rash. Avoiding sulfonamide medications is also recommended.

Comparison: Hartnup Disease vs. Nutritional Pellagra


Feature	Hartnup Disease	Nutritional Pellagra
Cause	Genetic mutation in the SLC6A19 gene affecting tryptophan transport.	Inadequate dietary intake of niacin.
Tryptophan Availability	Systemic deficiency due to malabsorption and loss in urine.	Typically normal, assuming dietary intake is adequate.
Symptom Triggers	Poor nutrition, sunlight exposure, stress, certain medications.	Primarily poor nutrition and inadequate niacin intake.
Inheritance	Autosomal recessive.	Not inherited; purely environmental/dietary.
Diagnosis	Confirmed by finding neutral aminoaciduria via urine analysis.	Based on clinical symptoms and dietary history; responds to niacin supplementation.

Conclusion

Hartnup disease is a prime example of how a seemingly straightforward nutrient deficiency can have a complex genetic origin. The condition ultimately results in a deficiency of vitamin B3 (niacin) because of a defect in the transport of its amino acid precursor, tryptophan. While the symptoms closely mimic those of nutritional pellagra, the underlying cause is an inherited metabolic error. Thankfully, with proper diagnosis, dietary management, and vitamin supplementation, affected individuals can often lead normal lives, and the frequency and severity of symptomatic attacks tend to decrease with age.

For more in-depth information, you can consult the reliable resource from MedlinePlus: Hartnup disease: MedlinePlus Genetics.

Frequently Asked Questions

The primary cause of symptoms in Hartnup disease is a deficiency of vitamin B3, or niacin, which occurs because a genetic defect prevents the body from properly absorbing the amino acid tryptophan needed for its synthesis.

Hartnup disease is typically diagnosed through a urine test that reveals excessive amounts of neutral amino acids, a condition known as neutral aminoaciduria.

Yes, a high-protein diet is a cornerstone of managing Hartnup disease. It provides alternative sources of amino acids and supports nutrient absorption via unaffected pathways, helping to prevent symptomatic episodes.

Hartnup disease is a lifelong genetic condition and is not curable. However, it is manageable with proper diet, supplementation with niacin, and avoidance of triggers to minimize the frequency and severity of symptoms.

The skin rash, a form of dermatitis, is a symptom of the niacin deficiency that results from Hartnup disease. This rash is photosensitive, meaning it appears on sun-exposed areas of the skin, a classic sign of pellagra.

Tryptophan is an amino acid and a precursor for niacin synthesis. In Hartnup disease, defective transport in the intestines and kidneys leads to malabsorption and loss of tryptophan, which directly results in a deficiency of niacin.

Yes, Hartnup disease is inherited in an autosomal recessive pattern. This means a child must inherit a mutated copy of the responsible gene, SLC6A19, from both parents to be affected.

No, many individuals with Hartnup disease remain asymptomatic throughout their lives, especially if they maintain a good diet. Symptoms are often intermittent and triggered by stressors or poor nutrition.