1. Background

• tyrosine aminotransferase (TAT):
  • rate limiting enzyme in tyrosine metabolism
  • found predominantly in the liver
  • transaminates tyrosine to p-OH-phenylpyruvic acid
• disorder first described in 1938 and connection to tyrosine metabolism established in 1973

2. Genetic Defect

• mutation in the gene coding for TAT -> accumulation of tyrosine
• tyrosine levels in the plasma and tissues excede saturation
• formation of long, slender, birefringent tyrosine crystals intracellularly -> accumulate in the eyes and skin -> stimulate an inflammatory response with PMN leukocytes, edema, neovascularization -> ocular and skin lesions
• liver and renal functions are not affected
• in TYROSINEMIA-II, the damage is not done by the build-up of tyrosine but by its metabolites while in TYROSINEMIA-III, the damage is done by tyrosine directly

1. Ocular Manifestations

• appear during the first few months of life:
  • lacrimation, photophobia, redness
  • corneal herpetiform erosins/ulcers
  • dendritic ulcers
  • corneal and conjunctival plaques
  • neovascularization
• long-term complications:
  • cataracts, corneal scarring, exodeviation, glaucoma, nystagmus, opacifications, visual impairment

2. Cutaneous Manifestations

• begin with or after the ocular manifestations
• skin lesions:
  • begin as blisters or erosions -> crust -> hyperkeratotic
  • painful, nonpruritic, sometimes hyperhidrosis
  • limited to palms and soles (particularly tips of digits, thenar and hypothenar eminences)
  • appear linear or subungual

3. Neurological Manifestations

• normal intelligence -> moderate mental retardation
• self-mutilating behaviour
• disturbances of fine coordination

1. Serum

• tyrosinemia is diagnostic (levels higher than in TYROSINEMIA-II)

2. Urine

• tyrosinuria and tyrosyluria
• elevated tyrosine metabolites
• no other amino acids elevated

3. Liver Biopsy

• decreased TAT activity

1. Diet

• low tyrosine and phenylalanine diet
• can correct tyrosinemia
• results in a draumatic and rapid healing of eye and skin lesions and can prevent mental retardation