Introduction

Menkes disease is a lethal multisystemic disorder of copper metabolism, which is inherited as an X-linked recessive trait. Progressive neurodegeneration and connective tissue manifestations, together with a peculiar ‘kinky’ hair, are the main manifestations. Most of the clinical features can be explained by malfunction of one or more important copper-dependent enzymes. Many patients exhibit a severe clinical course, but variable forms are distinguished; the occipital horn syndrome is the mildest recognized form. The defective gene in Menkes disease (ATP7A) is predicted to encode an energy-dependent copper export pump (ATP7A), which is involved in the delivery of copper to the secreted copper enzymes and in the export of surplus copper from cells. Diagnosis of Menkes disease can be established by copper accumulation studies or by DNA mutation analysis. A cure for the disease does not exist, although early copper–histidine treatment may correct some of the neurological symptoms.

Normal and abnormal copper metabolism in human and other organisms has been the focus of extensive research, and tremendous knowledge has been accumulated in the recent years. Several aspects of Menkes disease and copper homeostasis have been reviewed extensively and the reader is referred to these manuscripts for the original references (Hart, 1983; Horn et al., 1992, 1995; Kaler, 1994; Danks, 1983, 1993, 1995; Tümer & Horn, 1996, 1997, 1999; Pena et al., 1999; Horn & Tümer, 2002).

Clinical manifestations

Menkes disease (MD) is a multisystemic disorder dominated by neurological symptoms and connective tissue disturbances.