Hartnup disease is a rare disease due to abnormal absorption and excretion of tryptophan and other amino acids. Symptoms are rash, CNS abnormalities, short stature, headache, and collapsing or fainting. Diagnosis is by high urinary content of tryptophan and other amino acids. Prevention is with niacinamide or niacin, and attacks are treated with nicotinamide.
Hartnup disease is caused by a mutation in the Na-dependent neutral amino acid transporter gene 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 GI 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
Although the disorder is present from birth, symptoms may manifest in infancy, childhood, or early adulthood. Symptoms may be precipitated by sunlight, fever, drugs, or other stresses.
Poor nutritional intake nearly always precedes appearance of symptoms. Symptoms and signs are due to niacinamide deficiency and resemble those of pellagra (see Vitamin Deficiency, Dependency, and Toxicity: Niacin Deficiency), 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.
Diagnosis is made by showing the characteristic amino acid excretion pattern in the urine. Indoles and other tryptophan degradation products in the urine provide supplementary evidence of the disease.
Prognosis is good, and frequency of attacks usually diminishes with aging. The number and severity of attacks can be reduced by maintaining good nutrition and supplementing the diet with niacin or niacinamide 50 to 100 mg po tid. Attacks may be treated with nicotinamide 20 mg po once/day.
Last full review/revision September 2009 by Peter C. Brazy, MD
Content last modified August 2010