At least three specific small bowel enterocyte apical transport proteins appear to be involved in the absorption of amino acids in the diet. In Hartnup Disease, the intestinal and renal absorption of tryptophan is defective. Tryptophan is an essential amino acid and a precursor for nicotinic acid, serotonin, and melatonin. The clinical manifestations of Hartnup disease are primarily due to the malabsorption of tryptophan, resulting in niacin deficiency, because niacin is synthesized from tryptophan.

Most children with Hartnup disease are asymptomatic, but some children experience photosensitivity and pellagra-like skin rashes. Neurologic involvement can occur most commonly leading to ataxia. Neurologic and skin symptoms typically wax and wane during the course of this disease. The main laboratory finding in Hartnup disease is aminoaciduria, restricted to the neutral amino acids (alanine, serine, threonine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, and histidine). The urinary excretion of proline, hydroxyproline, and arginine remains unchanged, and this important finding differentiates Hartnup from other causes of generalized aminoaciduria such as Fanconi syndrome. The treatment with nicotinic acid or nicotinamide and high-protein diet generally results in significant improvements of symptoms.