Hartnup disease is a rare autosomal recessive disease involving malabsorption and increased renal excretion of tryptophan and other amino acids. Also, conversion of tryptophan to niacinamide is impaired. Symptoms are rash, central nervous system abnormalities, short stature, headache, and collapsing or fainting. Diagnosis is by high urinary content of tryptophan
Hartnup disease is caused by a mutation in the sodium-dependent neutral amino acid transporter gene (SLC6A19) that is expressed in kidney and intestinal epithelia. It is inherited as an autosomal recessive trait.
Small-bowel malabsorption of tryptophan, phenylalanine, methionine, and other monoaminomonocarboxylic amino acids occurs. Accumulation of unabsorbed amino acids in the gastrointestinal tract increases their metabolism by bacterial flora. Some tryptophan degradation products, including indoles, kynurenine, and serotonin, are absorbed by the intestine and appear in the urine. Renal amino acid resorption is also defective, causing a generalized aminoaciduria involving all neutral amino acids except proline and hydroxyproline. Conversion of tryptophan to niacinamide is also defective.
Symptoms and Signs of Hartnup Disease
Although the disorder is present from birth, symptoms of Hartnup disease may manifest in infancy, childhood, or early adulthood. Symptoms may be precipitated by sunlight, fever, medications, or other stresses.
Poor nutritional intake nearly always precedes appearance of symptoms. Symptoms and signs are due to niacin deficiency and resemble those of pellagra, particularly the rash on parts of the body exposed to the sun; mucous membrane and neurologic symptoms also occur. Neurologic manifestations include cerebellar ataxia and mental abnormalities. Intellectual disability, short stature, headache, and collapsing or fainting are common. Psychiatric symptoms, including emotional lability and psychosis, also occur.
Diagnosis of Hartnup Disease
Urine testing for amino acids
Diagnosis of Hartnup disease is made by showing the characteristic amino acid excretion pattern in the urine—an increased amount of neutral amino acids except for proline and hydroxyproline. These neutral amino acids include alanine, asparagine, citrulline, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tryptophan, tyrosine, and valine (1).
Indoles and other tryptophan degradation products in the urine provide supplementary evidence of the disease. Molecular genetic testing can be done to confirm the diagnosis of Hartnup disease in some patients.
Diagnosis reference
1. National Organization for Rare Disorders (NORD): Hartnup Disease. Accessed January 18, 2024.
Treatment of Hartnup Disease
Niacin or niacinamide supplements
Nicotinamide for attacks
Attacks may be treated with oral nicotinamide 20 mg once a day.
Patients who have Hartnup disease also should avoid sun exposure as well as antibiotics that contain sulfonamides.
Prognosis for Hartnup disease is good, and frequency of attacks usually diminishes with age.
