In Hartnup disease, the transport of amino acids (the building blocks of proteins) in the intestine and kidneys is disordered. Hartnup disease occurs when a person inherits two copies of the abnormal gene for the disorder, one from each parent (see Figure: Non–X-Linked (Autosomal) Recessive Disorders). The defective gene controls the absorption of certain amino acids from the intestine and the reabsorption of those amino acids in the kidneys. Consequently, a person with Hartnup disease cannot absorb amino acids properly from the intestine and cannot reabsorb them properly from tubules in the kidneys.
Excessive amounts of amino acids, such as tryptophan, are excreted in the urine. The body is thus left with inadequate amounts of amino acids. With too little tryptophan in the blood, the body is unable to make a sufficient amount of the B-complex vitamin niacin, particularly under stress when more vitamins are needed.
Symptoms
The intestines and kidneys function normally, aside from the problem transporting amino acids, and the effects of the disease occur mainly in the brain and skin. Although the disorder is present at birth, symptoms of Hartnup disease may begin in infancy or childhood, but sometimes they begin as late as early adulthood. Symptoms may be triggered by sunlight, fever, drugs, or emotional or physical stress.
A period of poor nutrition nearly always precedes an attack. Most symptoms occur sporadically and are caused by a deficiency of niacin. The symptoms resemble those caused by a dietary deficiency of niacin (pellagra), particularly the rash that develops on parts of the body exposed to the sun. Intellectual disability, short stature, headaches, an unsteady gait, and collapsing or fainting are common. Psychologic problems (such as anxiety, rapid mood changes, delusions, and hallucinations) may also result.
Diagnosis
Prognosis
Treatment
People with Hartnup disease can reduce the number and severity of attacks by maintaining good nutrition and eating enough protein and supplementing their diet with niacinamide or niacin (a B-complex vitamin very similar to niacinamide).
People may take nicotinamide to treat attacks.
People who have Hartnup disease also should avoid sun exposure as well as antibiotics that contain sulfonamides.
