Hartnup Disease

Pathogenesis
  • Hartnup disease is caused by a mutation in the protein responsible for proximal tubule and gastrointestinal transport of neutral amino acids such as tryptophan. The inability of the kidneys and the GI system to transport tryptophan causes two derangements. Firstly, tryptophan remains in the intestinal lumen and is converted by bacteria into compounds that are toxic to the CNS, resulting in cerebellar ataxia. Secondly, renal loss of tryptophan, a metabolic precursor of niacin, can lead to niacin-deficiency and thus pellagra-like manifestations in the skin.
  • Hartnup disease is inherited in an autosomal recessive fashion.