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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 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,
Signs, and Diagnosis
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. Neurologic manifestations include cerebellar ataxia and mental abnormalities. Mental retardation, short stature, headache, and collapsing or fainting are common. 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.
Diagnosis is made by demonstrating the characteristic amino acid excretion pattern in the urine. Indoles and other tryptophan degradation products in the urine provide supplementary evidence of the disease.
Treatment
Prognosis is good, and frequency of attacks usually diminishes with aging. Attacks can be prevented 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 November 2005
Content last modified November 2005
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