Tyrosinemia II: lessons in molecular pathophysiology

Area of Science:

• Biochemistry
• Genetics
• Dermatology

Background:

• Tyrosinemia II stems from a deficiency in hepatic tyrosine aminotransferase, a key enzyme in tyrosine catabolism.
• This deficiency leads to elevated plasma tyrosine levels and increased urinary tyrosine metabolites.

Observation:

• Increased plasma tyrosine causes crystallization in the cornea, leading to ulcerations and epithelial proliferation.
• In the skin, elevated tyrosine results in erosions, crusting, and hyperkeratosis of the palms and soles.

Findings:

• The human disease is an autosomal recessive genetic disorder, with similar conditions observed in mink and dogs.
• A nutritional model using rats fed a high-tyrosine, low-protein diet replicates the key features of Tyrosinemia II.

Implications:

• This review discusses the features of Tyrosinemia II and its broader implications for understanding other genetic diseases.
• The study highlights the utility of animal models in elucidating the mechanisms of human genetic disorders.