Hartnup

Hartnup disease, also known as Hartnup syndrome, is a rare autosomal recessive metabolic disorder caused by mutations in the SLC6A19 gene, which encodes the neutral amino acid transporter B0AT1 expressed in enterocytes of the small intestine and proximal tubules of the kidney. The defect leads to impaired absorption and reabsorption of neutral amino acids, notably tryptophan, resulting in neutral aminoaciduria and low plasma levels of neutral amino acids.

Because tryptophan is a key precursor for nicotinamide (niacin), deficiency of tryptophan can cause pellagra-like symptoms: photosensitive dermatitis in sun-exposed areas, as well as cerebellar ataxia, dizziness, headaches, and cognitive or psychiatric disturbances. Some individuals are asymptomatic or present with intermittent symptoms, especially during periods of poor nutrition or illness.

Diagnosis is suggested by persistent neutral aminoaciduria with low plasma levels of neutral amino acids, and by improvement on niacin therapy. Genetic testing can identify mutations in SLC6A19.

Treatment focuses on preventing niacin deficiency and supporting amino acid balance: a high-protein diet with adequate calories, nicotinamide (niacin) supplementation, and avoiding sun exposure where dermatitis occurs. Some patients may benefit from targeted tryptophan supplementation, though this is used cautiously.

Prognosis varies; with appropriate nutritional and niacin therapy, many individuals experience symptom improvement, though some neurological signs may persist if treatment is delayed. Hartnup disease remains a lifelong condition requiring ongoing dietary and, when necessary, pharmacological management.