X-LINKED DOMINANT ICHTHYOSIS WITH PEROXISOMAL DEFICIENCY - AN ULTRASTRUCTURAL AND ULTRACYTOCHEMICAL STUDY OF THE CONRADI-HUNERMANN SYNDROME AND ITS MURINE HOMOLOG, THE BARE PATCHES MOUSE

Background and Design: The bare patches (Bpa) mouse expresses an X-dominant disorder that may be homologous to the Conradi-Hunermann (CH) syndrome in man; ie, both express ichthyosis, cataracts, and skeletal defects. To confirm their homology, we compared the light and electron microscopy of involved (1) vs uninvolved (U) skin from an infant with CH syndrome to Bpa mice during and after resolution of the scaling disorder. The peroxisomal content of Bpa and CH skin was evaluated by diaminobenzidine (DAB) ultracytochemistry (Bpa only) and by assessment of catalase (Bpa only) and dihydroxyacetone phosphate-acyltransferase (DHAP-AT) activities in cultured I vs U fibroblasts. Results: Both CH and Bpa I epidermis exhibited psoriasiform features. In addition, ultrastructurally both exhibited the following: (1) vacuolated lamellar bodies (2) dilatation of intercellular spaces by vesicular structures and amorphous debris, and (3) abnormal mitochondria. Stratum corneum interstices were filled with vesicular structures, and no lamellar unit structures were evident using ruthenium tetroxide postfixation. Peroxisomes were poorly stained by DAB in I Bpa epidermis and dermis during the eruptive phase. Moreover, catalase and DHAP-AT activities in cultured I Bpa fibroblasts were decreased to 40% and 30% of U Bpa levels, respectively; DHAP-AT activity in cultured I CH fibroblasts was also reduced (60% of U CH). With resolution of the scaling disorder, the ultrastructural and ultracytochemical features of I and U Bpa skin became indistinguishable. Conclusions: These studies provide evidence for a self-resolving defect involving multiple organelles, including lamellar bodies, peroxisomes, and mitochondria in the I skin of CH syndrome and the Bpa mouse.