1. Background

• tryptophan
  • an essential amino acid and precursor for nicotinamide and serotonin
  • tryptophan accumulated in the small intestine is metabolized by the intestinal flora to indican-related metabolic products which are reabsorbed by the gut and then metabolized in the liver and excreted as indican in the urine in large quantities
  • failure to absorb tryptophan results in a tryptophan deficiency -> failure to convert tryptophan to nicotinamide -> nicotinamide deficiency -> pellagra-like rash
• other neutral amino acids:
  • glutamine, histidine, valine, phenylalanine, tryptophan, leucine, asparagine, citrulline, isoleucine, alanine serine, threonine

2. Genetic Defect

• genetic defect -> defect in the transport of neutral amino acids across the proximal renal tubules and the small intestine -> massive aminoaciduria and neutral amino acids in the feces - the transport of nonneutral amino acids is unaffected - highly variable phenotypic expression of this disease may be due to environmental factors such as nutritional state as many cases are asymptomatic (but become symptomatic if the plasma concentration of amino acids decreases drastically)
• genetic heterogeneity probably exists as the renal and intestinal defects may occur separately or together
• maternal Hartnup Disease is likely benign to the fetus

1. Episodic

• triggered by stress, infections, exposure to sunlight, sulfonamides, diarrhea, low-protein diet
• progress over several days and last from 1-4 weeks before spontaneous remission
• may be characterized by long periods of remission
• vary in intensity but tend to be less severe with age
• each episode may be characterized by neurological and/or cutaneous manifestations
• neurological manifestations may precede cutaneous features by years

2. Neurological Manifestations

3. Ocular Manifestations

• double vision
• nystagmus
• photophobia
• strabismus

4. Cutaneous Manifestations

1. Urine Chromatography

• excessive levels of neutral amino acids and indican in the urine in the presence of normal levels in the serum is diagnostic for
• Hartnup Disease

2. Jejunal Biopsy

• transport defect may be identified in vitro

1. Medical

• Nicotinic Acid (25mg/d)
• improved dietary intake - high protein diet