Inherited metabolic disorder with clinical expression
in males only. Caused by defective intestinal copper absorption that results
in severe mental retardation, failure to thrive, sparse hair, and
Menkes Disease; Menkes
Syndrome; Steely Hair Syndrome.
Worldwide the incidence is estimated at 1:300,000 in the general
population, however, in Australia the condition occurs in 1:35,000 in the general
X-linked recessive; caused by a mutation in the
gene encoding Cu2+-transporting ATPase, alpha polypeptide (gene map
locus is Xq12-q13).
Defective coding for an intracellular
copper-transporting protein called MNK, which travels between the Golgi
apparatus and the cell membrane, transporting copper to the exterior of the
cell. Defective MNK prevents proper intestinal absorption of copper.
The resultant free-copper deficiency affects the function of copper-dependent
enzymes such as cytochrome oxidase, tyrosinase, and lysyl oxidase, which
results in symptoms and signs of disease.
Should be considered in any male infant with unexplained
seizures, hypothermia, and mental retardation. Serum copper and
ceruloplasmin concentrations are low. The copper levels are elevated in
fibroblasts and the placenta. Carrier status for the abnormal gene usually
can be determined by microscopic examination of multiple hairs from
scattered scalp sites for pili torti (twisted hair). Prenatal diagnosis is
available (DNA probe).
Intrauterine growth retardation, which persists
after birth. Neurologic deterioration begins approximately 2 months after
birth. Focal cerebral and cerebellar degeneration progress rapidly to
decerebration, with characteristic hypotonia, spasticity, and partial and
Strabismus, myopia and poor visual acuity are common findings.
Abnormal thermoregulation with resultant hypothermia is common.
Microcephaly occurs as a result of gliosis. The hair is sparse, dull,
hypopigmented, brittle, and twisted (pili torti). Hypotonus of the facial
musculature gives a chubby-cheek appearance. Micrognathia may be present.
Typically, the long bones are osteoporotic. Blood vessels (systemic arteries) become long and
tortuous with irregular lumens because of abnormal development of the
elastic lamina and thickening of the intima. Aneurysms subsequently develop that may lead to
subdural, cerebral, and intestinal hemorrhages. Orthostatic
hypotension may develop. The skin is thick and dry and has irregular
pigmentation. These patients may also suffer from gastroesophageal reflux with recurrent
aspiration pneumonias. Chronic diarrhea is common. Death usually occurs
in early childhood (at around two years of age). Parenteral injections of copper-histidine may slow
the disease progression and prevent neurologic signs.
Anticonvulsant therapy should be
assessed and optimized preoperatively and continued throughout the
perioperative period. Consider raised intracranial pressure if previous
intracranial hemorrhage. Repeated aspiration pneumonias plus hypotonia may
compromise respiratory function. A chest radiograph,
arterial blood gases, and other tests may be required. Rule out ongoing pneumonia. Check for
anemia secondary to aneurysmal bleeding. Hypovolemia and/or electrolyte
disturbances may be present if diarrhea is severe. Postural vital signs to
check for orthostatic hypotension.
Pretreatment with H2-antagonists
and/or metoclopramide to reduce the risk of reflux and aspiration. Consider
rapid-sequence induction, although ...