Aminoaciduria, Hartnup disease

Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan and other large neutral amino acids. The result is that the intestinal absorption of free tryptophan is impaired, although dipeptide absorption is normal. There is a considerable urinary loss of tryptophan (and other amino acids) as a result of the failure of the normal reabsorption mechanism in the renal tubules - renal aminoaciduria. In addition to neurological signs that can be attributed to a deficit of tryptophan for the synthesis of serotonin in the central nervous system, the patients show clinical signs of pellagra, which respond to the administration of niacin. 

Metabolic studies by Milne et al. (M8) showed that in Hartnup disease the renal aminoaciduria is more constant than the excessive excretion of indican and indolic acids (indoleacetic acid, indolelactic acid, and indoleacetylglutamine). After ingestion of L-tryptophan in this disease there is usually delayed and incomplete absorption from the gut of the amino acid which is partly converted, by intestinal bacteria, to indole... 

The Hartnup disease described in 1956 (B2) under the title hereditary pellagra-like skin rash with temporary cerebellar ataxia, constant renal aminoaciduria, and other bizarre biochemical features evidently belongs to the diseases related to inborn errors of metabolism due to inherited differences. As was pointed out by Harris (H3), very often the detection of urinary amino acid metabolites has represented the starting point of the investigation of different genetic biochemical disorders. A recent study (A8) showed that the excess production of indole by colon bacteria in 15 cases of Hartnup disease was due entirely to an increased amount of tryptophan contained in the large bowel, and not to an abnormality of the bacteria themselves. 

Williams and Sweeley (1964) have given methods for the chromatographic separation of many urinary aromatic acids and have discussed diagnostic applications to (1) secreting tumors, e.g., malignant carcinoid, pheochromocytoma, and neuroblastoma, and (2) inborn errors of metabolism, e.g., tyrosinosis, phenylketonuria, Hartnup disease (involves aminoaciduria), and other inherited diseases. These authors referred to the use of infrared spectroscopy for verification of the identity of fractions of volatile organic anesthetics in blood. Chlorpromazine, pentobarbitone, and amphetamine, are examples of pharmacological substances that have been separated (Scott, 1966). 

Aminoacidurias may be generalized, when there is excessive secretion of several non-related amino acids, or specific, when there is excess excretion of a single amino acid or a related group of them (as in cystinuria or Hartnup disease). 

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