Menkes disease (Kodama and Murata 1999). Like Menkes, OHS is recessively inherited and characterized by abnormalities in copper metabolism (Proud et al. 1996). Whereas the prevalence rate of Menkes disease appears to be 1 in 100,000–250,000 births, the prevalence rate of OHS appears to be much less. For example, only a few cases have been reported in Japan (Kodama et al. 1999).

Although Menkes and OHS have a similar abnormality in copper metabolism, the two diseases have different clinical presentations and survival potentials (Das et al. 1995). Because of late and inconsistent onset of symptoms, OHS might escape early recognition. A patient must be at least 2 years of age before a definitive diagnosis of OHS is possible (De Paepe et al. 1999). A prominent protuberance (exostoses) in the occipital bone seen on radiographs defines the condition (Proud et al. 1996). That protuberance is not seen in patients with classical Menkes disease. Additional skeletal abnormalities are short and broad clavicles, osteoporosis, laxity of the skin and joints, and bladder diverticula (Kodama et al. 1999). Serum copper and ceruloplasmin are low in some but not all patients, and cultured skin fibroblasts typically have low lysyl oxidase activity. Although disturbance in electroencephalogram patterns are seldom seen, arrested mental development and late-onset seizures often accompany the disease. Most OHS patients suffer inguinal hernias, recurrent diarrhea, urinary-tract infections, and distorted facial features, such as high foreheads and hooked noses. Radiographs show tortuous cerebral blood vessels with multiple branch occlusions (Proud et al. 1996). Although OHS patients can survive until adulthood, they have borderline intelligence. To date, no published reports have appeared describing parenteral administration of copper to correct, manage, or improve OHS patients (Kodama et al. 1999).

Studies of cells taken from OHS patients have linked MNK gene processing with the development of OHS. The human MNK gene normally has three 98-base pair (bp) tandem repeats in an upstream promoter region (Levinson et al. 1996). Genomic DNA from an OHS patient was found to have only 2 of the 98-bp repeats; no other mutations were found. The 98-bp deletion led to a dramatic decrease in the expression of a CAT reporter gene construct, suggesting that the 98-bp repeats play a role in regulating MNK mRNA expression (Levinson et al. 1996). Northern blot analysis, however, revealed no detectable reduction in MNK mRNA levels in cells derived from the patient. In another patient with OHS, an A–T transversion in intron 10 resulted in a loss of exon 10 by alternative splicing of ATP7A mRNA (Qi and Byers 1998). The mutated gene gave rise to an ATP7A variant that lacked two of the eight transmembrane domains and, for reasons not understood, remained resident in the endoplasmic reticulum and was not transported to the Golgi. To be effective in export,