Hartnup disease

Hartnup disease, or Hartnup disorder, is an autosomal recessive metabolic disorder affecting the absorption of neutral amino acids (particularly tryptophan that can be, in turn, converted into Serotonin, Melatonin and Niacin). Niacin is a precursor to nicotinamide, a necessary component of NAD+.

The causative gene, SLC6A19, is located on chromosome 5.

Hartnup disease
Tryptophan

Diagnosis

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, which are the building blocks of proteinches With too little tryptophan in the blood, the body is unable to make a sufficient amount of the B-complex vitamin niacinamide, particularly under stress when more vitamins are needed.

Causes

Hartnup disease is inherited as an autosomal recessive trait. Heterozygotes are normal. Consanguinity is common. In 2004, a causative gene, SLC6A19, was located on band SLC6A19 is a sodium-dependent and chloride-independent neutral amino acid transporter, expressed predominately in the kidneys and intestine.

Symptoms

Hartnup disease manifest during infancy with variable clinical presentation: failure to thrive, photosensitivity, intermittent ataxia, nystagmus and tremor.

Nicotinamide is necessary for neutral amino acid transporter production in the proximal renal tubules found in the kidney, and intestinal mucosal cells found in the small intestine. Therefore, a symptom stemming from this disorder results in increased amounts of amino acids in the urine.

Pellagra is also caused by low nicotinamide; this disorder results in dermatitis, diarrhea and dementia.

Hartnup disease is a disorder of amino acid transport in the intestine and kidneys; otherwise, the intestine and kidneys function normally, and the effects of the disease occur mainly in the brain and skinches Symptoms may begin in infancy or early 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. The attacks usually become progressively less frequent with age. Most symptoms occur sporadically and are caused by a deficiency of niacinamide. A rash develops on parts of the body exposed to the sun. Mental retardation, 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.

Treatment

A high-protein diet can overcome the deficient transport of neutral amino acids in most patients. Poor nutrition leads to more frequent and more severe attacks of the disease, which is otherwise asymptomatic Advise all patients who are symptomatic to use physical and chemical protection from sunlight. Avoiding excessive exposure to sunlight, wearing protective clothing, and using physical and chemical sunscreens are mandatory. Recommend sunscreens with a skin protection factor of 15 or greater. Advise patients to avoid other aggravating factors, such as photosensitizing drugs, as much as possible. In patients with niacin deficiency and symptomatic disease, daily supplementation with nicotinic acid or nicotinamide reduces the number and the severity of attacks. Neurologic and psychiatric treatment is needed in patients with severe CNS involvement.