Hartnup disease

Page most recently updated 7 September 2026

This page focuses on the reported psychiatric associations, which may be the initial presenting manifestation, and on other clinical features that may assist the psychiatrist or primary care physician in identifying the underlying diagnosis, considered through the lenses of the diagnostic lenses framework.

Hartnup disease is a rare genetic neurometabolic disorder of neutral amino acid transport, resulting in impaired intestinal and renal reabsorption of neutral amino acids. It occurs as an inherited autosomal recessive genetic condition; absence of a relevant family history does not exclude the diagnosis because the parents of an affected individual are typically unaffected carriers. A distinctive presentation may include the combination of photosensitive dermatitis, episodic neurologic symptoms, and psychiatric manifestations.

It can present with psychiatric features such as anxiety, depression, irritability, emotional lability, behavioural changes, confusion, and psychosis. Psychiatric manifestations may become apparent or clinically significant during adolescence or adulthood and may occur episodically, particularly during periods of nutritional deficiency, illness, fever, or other metabolic stress.

Other characteristic features include episodic cerebellar ataxia, gait disturbance, tremor, nystagmus, headaches, dizziness, and other neurologic symptoms resembling pellagra. Some individuals remain asymptomatic or have only mild manifestations. The neurologic and psychiatric manifestations may fluctuate and can improve with nutritional treatment.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

  • Renal/electrolytes: increased urinary loss of neutral amino acids and other renal aminoaciduria may occur; renal function is generally preserved.

  • Gastrointestinal: impaired intestinal absorption of neutral amino acids contributes to the disorder and may become clinically important during periods of nutritional stress.

  • Dermatologic: photosensitive pellagra-like dermatitis, particularly affecting sun-exposed areas, may occur and can include erythema, scaling, hyperpigmentation, and skin thickening.

Early diagnosis is important to recognize a potentially treatable cause of episodic neurologic and psychiatric symptoms, prevent recurrent manifestations through adequate nutritional support and avoidance of precipitating metabolic stressors, distinguish Hartnup disease from primary psychiatric or neurologic disorders, and reduce the risk of persistent neurologic or dermatologic complications.

Selected references and further reading — Multisystemic lens

Cardinal RN, Bullmore ET. The diagnosis of psychosis. Cambridge: Cambridge University Press; 2011.

Sachdev PS, Keshavan MS, editors. Secondary schizophrenia. Cambridge: Cambridge University Press; 2010.

Levenson JL, editor. The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. 3rd ed. Washington (DC): American Psychiatric Association Publishing; 2019.

Stern TA, Beach SR, Smith FA, Freudenreich O, Vranceau AM, Fava M, editors. Massachusetts General Hospital handbook of general hospital psychiatry. 8th ed. Philadelphia: Elsevier; 2025.

Arciniegas DB, Yudofsky SC, Hales RE, editors. The American Psychiatric Association Publishing textbook of neuropsychiatry and clinical neurosciences. 6th ed. Washington (DC): American Psychiatric Association Publishing; 2018.

Agrawal N, Faruqui R, Bodani M, editors. Oxford textbook of neuropsychiatry. Oxford: Oxford University Press; 2020.

Boland R, Verduin M, editors. Kaplan and Sadock's comprehensive textbook of psychiatry. 11th ed. Philadelphia: Wolters Kluwer; 2024.

Loscalzo J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 22nd ed. New York: McGraw Hill; 2025.