Menkes Disease is a genetic disorder affecting the metabolism of copper. Patient with this
disease are both physically and mentally retarded. Menkes disease is usually first detected
in the first 2-3 months of life. Infant males born with the disease fail to thrive,
experience hypothermia, have delayed development, and experience seizures. These infants
also have characteristic physical features such as changes of their hair and face. Females
may also have changes in hair and skin color, but rarely have significant medical problems.
Appropriate treatment of Menkes Disease requires that the disease be diagnosed early and
treatment started before irreversible brain damage occurs. The aim of treatment is to
bypass the normal route of absorption of copper through the gastrointestinal tract. Copper
must then be delivered to brain cells and be available for use by enzymes.
Copper histidine is a copper replacement that can be injected directly into the body to
avoid absorption through the gastrointestinal tract. However, studies have shown the
genetic abnormalities causing Menkes disease cannot simply be corrected by copper
The genetic abnormality causing Menkes disease can vary in its severity. Patients with a
genetic abnormality that may still permit some production of the enzymes required to process
copper may receive benefit from early treatment with copper replacement. However, patients
with severe abnormalities of the genes responsible for copper metabolism may receive no
benefit from copper replacement.
The purpose of this study is to continue to evaluate the effects of early copper histidine
in Menkes disease patients and to correlate specific molecular defects with responses to
Menkes disease is an X-linked recessive neurodegenerative disorder caused by defects in a
gene that encodes an evolutionarily conserved copper-transporting ATPase (ATP7A). Several
issues must be addressed in configuring therapeutic strategies for this disorder: (a)
affected infants must be identified and treatment commenced very early in life before
irreparable neurodegeneration occurs, (b) the block in intestinal absorption of copper must
be bypassed, (c) circulating copper must be delivered to the brain, and (d) copper must be
available to enzymes within cells that require it as a cofactor.
Very early, pre-symptomatic therapy with copper injections has been associated with improved
overall survival and, in some patients - based on their molecular defects, with vastly
better neurological outcomes in comparison to the usual natural history of this disorder.
The purpose of this study is to continue to provide early copper treatment to other newborn
infants diagnosed as having Menkes disease. We have established that three years duration of
treatment is adequate for prevention of neurodegeneration in this disorder.
- INCLUSION CRITERIA:
Newborn infants in whom Menkes disease is confirmed on biochemical or molecular grounds
and in whom no neurological symptoms are present are eligible for enrollment in this
Newly identified patients classified as symptomatic at the time of diagnosis, and affected
individuals with mild phenotypes are not currently eligible for this clinical trial.