Hartnup disease




Hartnup disease is also known as pellagra-like dermatosis.



It is an autosomal recessive metabolic disorder affecting the absorption of nonpolar amino acids 



People with Hartnup disease have a genetic disorder involving the renal, intestinal, and cellular transport processes for several amino acids, including tryptophan. 



The disease interferes with the absorption of tryptophan in the small intestine and increases its loss in the urine via the kidneys.



There is a generalized problem with amino-acid transport, caused by the causative gene, SLC6A19, located on band 5p15.33. 



SLC6A19 is a sodium-dependent and chloride-independent neutral amino acid transporter, expressed predominately in the kidneys and intestine.



As a result, the body has less available tryptophan to convert to niacin.



It particularly affects tryptophan absorption.



Tryptophan can 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 manifests during infancy:  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 Hertnup disorder results in increased amounts of amino acids in the urine. 



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



It is a disease of disordered  of amino acid transport in the intestine and kidneys



The intestine and kidneys function normally otherwise.



Hartnup disease effects occur mainly in the brain and skin. 



Symptom onset may be in infancy or early childhood.



Sometimes symptoms begin as late as early adulthood. 



Hartnup symptoms may be triggered by sunlight, fever, drugs, or emotional or physical stress. 



There is a period of poor nutrition that nearly always precedes an attack. 



With advancing age attacks become progressively less frequent.



Symptoms occur sporadically and the process is  caused by a deficiency of niacinamide. 



A rash develops on parts of the body exposed to the sun. 



It is commonly associated with mental retardation, short stature, headaches, unsteady gait, and fainting and psychiatric problems, such as anxiety, rapid mood changes, delusions, and hallucinations.



It is inherited as an autosomal recessive trait. 



Heterozygotes are normal. 



Consanguinity is common. 



There is increased presence of indoles, the bacterial metabolites of tryptophan, and tryptophan in the urine of patients as part of a generalized aminoaciduria of the disease. 



The excessive loss of tryptophan from malabsorption was the cause of the pellagra like symptoms. 



Its defective gene controls the absorption of certain amino acids from the intestine and the reabsorption of those amino acids in the kidneys. 



With Hartnup disease one 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 therefore excreted in the urine. 



With low tryptophan levels,  the blood, the body is unable to make a sufficient amount of the B-complex vitamin niacinamide, particularly under stress



Urinary excretion of proline, hydroxyproline, and arginine remains unchanged in Hartnup Disease, unlike 


other causes of generalized aminoaciduria, such as Fanconi syndrome. 



In Hartnup Disease increased 


increased levels of neutral amino acids: glutamine, valine, phenylalanine, leucine, asparagine, citrulline, isoleucine, threonine, alanine, serine, histidine, tyrosine, tryptophan and indican are found in the urine. 



A diet of high-protein can overcome the deficient transport of neutral amino acids in most patients with Hartnup disease.



Poor nutrition results in more severe attacks of the disease, which is otherwise asymptomatic. 



Symptomatic patients should use physical and chemical protection from sunlight, avoid excessive exposure to sunlight, wear protective clothing, use chemical sunscreens, and avoid photosensitizing drugs.



In patients with niacin deficiency and symptomatic disease, daily nicotinic acid or nicotinamide supplementation reduces both the number and severity of attacks. 



Neurologic and psychiatric treatment is needed in patients with severe central nervous system involvement.






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