RICHNER-HANHARTS SYNDROME - ULTRASTRUCTURAL ABNORMALITIES OF EPIDERMAL KERATINIZATION INDICATING A CAUSAL RELATIONSHIP TO HIGH INTRACELLULAR TYROSINE LEVELS

Richner-Hanhart''s syndrome (corneal dystrophies, palmoplantar keratoses and mental retardation) is caused by high levels of L-tyrosine in the blood, probably due to a defect of soluble tyrosine aminotransferase. Biopsies of skin lesions of 3 cases revealed peculiar ultrastructural changes that were not found in controls and have not been recorded before. Thickening of the granular layer and increased synthesis of tonofibrils and keratohyalin occurred in all cases. In the ridged palmar or plantar skin large numbers of microtubules and unusually tight packing of tonofibrillar masses were regularly demonstrable, the latter containing tubular channels of inclusions of microtubules. Increased cohesion and tight packing of tonofilaments could prevent normal spreading of keratohyalin and result in its globular appearance. No crystal formation was observed in epidermal keratinocytes nor was there lysosomal damage. A biochemical model to correlate these ultrastructural findings to known biochemical and clinical features is proposed. Excessive amounts of intracellular tyrosine enhance cross-links between aggregated tonofilaments and modulate the number and stability of microtubules.