COMPARISON OF TRACE-ELEMENT DISTRIBUTIONS IN OCCIPITAL HORN SYNDROME AND MENKES DISEASE WITH NORMAL SUBJECTS BY NEUTRON-ACTIVATION ANALYSIS

The concentrations of copper, arsenic, selenium, and manganese in auto psy samples of 19 different organs and tissue from a patient with occi pital horn syndrome (OHS) were determined in order to compare the trac e element distributions with those found in normal subjects. OHS is a mild, allelic form of Menkes disease, an X-linked recessive disturbanc e of the copper metabolism. It is clinically characterized by marked c onnective tissue features and specific skeletal abnormalities, includi ng cranial occipital horns. The diagnosis was confirmed by an increase d incorporation of radioactive copper into cultured fibroblasts, as we ll as a decreased activity of lysyl oxidase. All autopsy samples were analyzed by neutron activation analysis with radiochemical separation, and results were compared with those obtained by the same method from children with Menkes disease and from normal persons. The OHS patient showed significantly reduced arsenic concentrations in all tissues, w hereas the levels and distribution of Se and Mn were normal. The distr ibution of copper was distinctly abnormal, and very similar to that fo und in Menkes disease. Levels of Cu were low in spleen, brain, and liv er whereas accumulation in kidney and lung was evident. It was conclud ed that the genetic relationship between OHS and Menkes disease was cl early reflected in the trace element distributions in spite of the dif ference in lifespan of the patients. (C) 1996 Wiley-Liss, Inc.