The majority of patients with Hartnup disease are asymptomatic. The genetic defect is suspected in them only when a routine urinalysis shows the presence of aminoaciduria. Neutral hyper-aminoaciduria is the only consistent feature and so is the diagnostic marker for Hartnup disease . No intervention is indicated in asymptomatic individuals.
In symptomatic patients the initial sign is usually the distinctive pellagra-like skin rash. It occurs in late infancy or early childhood. The rash is identical to the rash in pellagra a disorder resulting from Vitamin B3 (niacin) deficiency . The rash is red and scaly, appearing on face, neck, hands, arms, and dorsal surface of the feet. The rash occurs after exposure to sunlight  .
Patients with Hartnup disease may experience some or all of the following symptoms :
The clinical manifestations are intermittent and inconsistent, and they usually improve spontaneously with age .
Exacerbations may occur after exposure to sunlight, usually in the spring or early summer . Symptoms may also be triggered by fever, drugs, and emotional or physical stress. These episodes develop over several days and last 1 to 4 weeks. Remission occurs spontaneous .
The physical examination of individuals with Hartnup disease should include particular attention to the skin. Skin findings may show :
Imaging studies are not indicated in Hartnup disease.
Differential diagnoses  :
Patients with Hartnup disease who are symptomatic may benefit from:
Treatment for Hartnup disease should include  :
Although Hartnup disease, as an inherited disorder, is always present, the symptoms are intermittent and vary from patient to patient. Many asymptomatic patients have only been diagnosed through routine screening, as aminoaciduria is always present .
Hartnup disease has a varied clinical picture. Most patients remain asymptomatic. The minority of patients with symptoms (skin rashes and photosensitivity, neurological and psychiatric disturbances) may be affected throughout their lives. These symptoms may interfere with their quality of life . Severe Central Nervous System involvement may occur rarely and may lead to death  . Mental retardation and delayed motor development, as well as growth retardation, have been seen in rare cases.
Recurrent exacerbations may occur when amino acid deficiency is increased due to other factors. These exacerbations become less frequent with age . Malnutrition and a low-protein diet are the primary factors causing clinical morbidity . The occurrence of symptoms in Hartnup disease is also affected by emotional stress, chronic illness, and severe diarrhea  .
Hartnup disease was first identified in members of the Hartnup family who had the symptoms of aminoaciduria, distinctive pellagra-like rash, and cerebellar ataxia. Hartnup disease is inherited as an autosomal recessive disorder requiring the defective gene from both parents. Carriers of the trait are asymptomatic .
The disease interferes with the absorption of neutral amino acids, particularly tryptophan, from the intestinal tract and it increases the excretion of them by the renal tubules   . All neutral amino acids are lost in urine and stool to varying degrees. Tryptophan is the most significant .
Individuals with Hartnup disease may be asymptomatic . Those who experience symptoms usually resolve over time. However symptoms may recur. Recurrent episodes most frequently are seen in the spring or early summer as a result of exposure to sunlight. The exacerbations can also be triggered by a febrile illness, poor nutrition, sulfonamides, emotional stress, and increased physical activity  .
The overall incidence of Hartnup disease is approximately 1 case per 30,000 births . Hartnup disease is considered one of the most common amino acid disorders . The disorder has been reported in all ethnic groups and equally in men and women .
The most common onset of symptoms in Hartnup disease is in early childhood (3-9 years of age). However, symptoms may occur as early as 10 days of age or as late as young adulthood  .
Hartnup disease is a metabolic disorder characterized by aminoaciduria due to abnormal renal and gastrointestinal transport of neutral amino acids (tryptophan, alanine, asparagine, glutamine, histidine, leucine, phenylalanine, tyrosine and valine)  . These compounds are necessary for optimal growth and bodyweight regulation and normal neurologic function .
Hartnup disease is an autosomal recessive abnormality . It has been determined that the gene responsible for the disorder is chromosome 5, band 5p15  . This gene mutation interferes with amino acid uptake by the epithelial cells of the intestinal mucosa and the permeability to them in the renal tubules . Approximately 10 separate mutations have been identified. The most common mutation, found in 43% of patients with Hartnup disorder, is c.517G→A, resulting in the amino acid substitution p.D173N  .
Neutral amino acid transport, primarily in the kidney and intestine, is dysfunctional in those who suffer from Hartnup disease. Amino acids from dietary sources, rather than being absorbed remain in the intestine. There they are converted by bacteria into compounds toxic to the central nervous system .
In the renal tubules they are excreted resulting in aminoaciduria  . The combined affect is the overall decrease in the availability of these necessary proteins. Tryptophan deficiency is the primary cause of symptoms. It is the precursor to many metabolites, serotonin in particular. Changes in serotonin metabolism may cause gastrointestinal dysfunction, mood abnormalities, and neurologic dysfunction. The action is not clearly understood  .
Tryptophan deficiency also leads to a decreased availability of this amino acid for the synthesis of niacin. It is believed that the main abnormalities associated with the disease result from niacin deficiency. They include the distinctive skin rash and reversible neurologic dysfunction .
Most patients are asymptomatic. Symptoms seem to occur when environmental, dietary, or constitutional factors further interfere with amino acid absorption . These factors are thought to include: acute diarrhea, malnutrition, and chronic illness .
Hartnup disease is a metabolic, inherited disorder. It is an autosomal recessive disease , meaning that both parents must have the trait in order for an individual to have the disease. It is characterized by an inability to metabolize certain neutral amino acids. Aminoaciduria is the one consistent feature. The symptoms of Hartnup disease result from an irregularity in the neutral amino-acid transport system where these proteins cross the epithelium of the renal tubules and intestine .
Hartnup disease was named for the English family in which the disorder was identified in 1956 .
Individuals with the disease are generally asymptomatic. However, those who are symptomatic may experience a distinctive pellagra-like rash, nervous system abnormalities such as ataxia, and psychiatric symptoms . Symptoms may be transient with occasional exacerbations . Malnutrition and a low-protein diet are the primary factors that contribute to symptomatology  .
What is Hartnup disease?
Hartnup disease is a genetic disorder affecting the absorption of certain amino acids. Individuals with the disease have resulting deficiencies of these proteins necessary for normal growth and nervous system development.
The symptoms of Hartnup disease are usually transient and self-limited. However, reoccurrences may occur. These , too, are limited and usually resolve in 1 to 4 weeks.
What causes Hartnup disease?
Hartnup disease is an autosomal recessive disorder. This means that the defective gene is inherited from both parents, each having the disease or the trait for Hartnup Disorder.
What are the symptoms?
Though most often asymptomatic, individuals with Hartnup disease may experience:
Who gets Hartnup disease?
Although the disease is inherited, not all individuals with the defective gene are symptomatic. Symptoms most commonly present in infancy or early childhood. However, those with the gene may become symptomatic at any age when exposed to certain risk factors. These include:
How is it diagnosed?
Hartnup disease is suspected when the patient presents with the distinctive rash. The disorder may also be suspected when routine lab work shows aminoaciduria (the presence of certain proteins in the urine).
How is Hartnup disease treated?
Hartnup disease is treated symptomatically as there is no cure. Increasing the dietary intake of essential amino acids, avoiding sun exposure, and the replacement of nutritional deficiencies, are the primary treatments for those individuals who are experiencing symptoms.
What are the complications?
The possible complications of Hartnup disease include the following:
What can we do to prevent the complications of Hartnup disease?
Exacerbations of Hartnup disease can be prevented by the following: