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.
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, 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, 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 also occur, including emotional lability and psychosis.
The number and severity of attacks can be reduced by maintaining good nutrition and supplementing the diet with oral niacin or niacinamide 50 to 100 mg 2 times a day.
Attacks may be treated with oral nicotinamide 20 mg once a day.
Prognosis is good, and frequency of attacks usually diminishes with age.
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