Hartnup Disease Overview

Serotonin and Hartnup Disease

• Tryptophan is converted to serotonin by argentaffin cells in the intestine
• Serotonin is carried through the body primarily by platelets
• Degradation product of serotonin is 5-Hydroxyindoleacetic Acid (5-HIAA) and is excreted in the urine
• Elevated levels of 5-HIAA in urine can indicate Argentaffin cell tumors
• Dietary restrictions are necessary as serotonin is found in foods like bananas, pineapples, and tomatoes
• Certain medications like phenothiazines and acetanilids should be withheld for 72 hours prior to specimen collection

Cystine Disorders

• There are two distinct disorders of cystine metabolism: Cystinuria and Cystinosis
• Both disorders are inherited and may have a noticeable odor of sulfur in the urine
• Cystinuria is marked by elevated amounts of cystine in the urine due to a defect in renal tubular transport

Cystinuria

• Inability of renal tubules to reabsorb cystine leads to formation of renal calculi
• Two modes of inheritance:
  • Cystine, lysine, arginine, and ornithine are not reabsorbed
  • Inheritance pattern is autosomal recessive
  • 65% of individuals can be expected to produce calculi early in life
• Diagnosis involves using culture media containing beta-2-thienylalanine and Bacillus subtilis

Tyrosyluria

• Urine may contain excess tyrosine or its degradation products, phydroxyphenylpyruvic acid and p-hydroxyphenyllactic acid
• Three types of Tyrosyluria:
  • Type 1: Deficiency in fumarylacetoacetate hydrolase (FAH) leading to generalized renal tubular disorder and liver failure
  • Type 2: Lack of tyrosine aminotransferase leading to corneal erosion and lesions on palms, fingers, and soles
  • Type 3: Lack of p-hydroxyphenylpyruvic acid dioxygenase leading to mental retardation
• Nitroso-naphthol test produces an orange-red color

Melanuria

• Indicates the overproliferation of melanocytes producing a metastatic malignant melanoma
• Darkening appears after the urine is exposed to air
• Corneal dystrophy and gelatinous drop-like melanuria are associated with Melanuria

Tryptophan Disorders

• Metabolites of tryptophan metabolism include indican and 5-Hydroxyindoleacetic acid (5HIAA)
• Tryptophan metabolism involves:
  • Tryptophan being absorbed in the intestine for protein synthesis or converted to indole by bacterial flora
  • Indole being reabsorbed into the bloodstream and converted to indican in the liver
  • Indican being excreted in the urine, which is colorless until oxidized to indigo blue by exposure to air
• "Blue diaper syndrome" can be an early indicator of Hartnup disease