Genetic disorder of copper metabolism beginning before
birth. Copper accumulates in excessive amounts in the liver and is deficient
in most other tissues of the body. Structural changes occur in the hair,
brain, bones, liver, and arteries. Other clinical features include spontaneous
hypothermia, severe developmental delay, loss of early development skills,
and seizures. Spontaneous subdural hematoma and/or rupture or thrombosis of
arteries in the brain may occur. Spastic dementia may eventually arise.
Osteoporosis as a result of abnormal copper metabolism can result in
pathologic fractures. The combination of subdural hematoma and bone
fractures may lead to an incorrect diagnosis of child abuse. Emphysema,
bladder abnormalities, degeneration of the retina, and cysts of the iris
have been described.
Kinky Hair Disease; Steely Hair Disease; X-Linked Copper
Neurodegenerative and connective tissue disorder first
described by John H. Menkes, an American neuropediatrician, in 1962.
In the early 1970s, an incidence of 1:35,000 male
births was suggested. However, in the 1980s, this frequency was reviewed at
1:90,000 live births. Finally, most agree that the incidence is estimated at
1:50,000-100,000 live births.
X-linked recessive. Caused by mutation in the
gene encoding the Cu2+-transporting ATPase α-polypeptide.
Gene map locus is X-q12-q13.
Defective coding for an intracellular
copper-transporting protein called the human Menkes protein (MNK or ATP7A), 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.
Resultant free-copper deficiency affects function of copper-dependent
enzymes such as cytochrome oxidase, tyrosinase, and lysyl oxidase, which
results in symptoms and signs of disease.
Menkes syndrome should be considered in any male infant
with unexplained seizures, hypothermia, and mental retardation. Hair changes
(stubby, tangled, sparse, steely, or kinky hair that is easily broken), low
serum copper and ceruloplasmin concentrations, and radiologic findings are
characteristic. Copper levels are elevated in fibroblasts and the placenta.
Carrier status for the abnormal gene can usually be determined by
microscopic examination of multiple hairs from scattered scalp sites for
pili torti (twisted hair). Prenatal diagnosis is available (DNA probe).
In the classic form, the disease starts before
age 3 months by loss of neurologic development (hypotonia progressively
evolving to spasticity), severe seizures, and subdural hematoma. Patients
manifest hypopigmentation, growth failure, skeletal defects, arterial
aneurysms, and progressive cerebral and cerebellar degeneration. Myoclonic
seizures and hypothermia are frequent. Fragile steely depigmented (grayish
or ivory colored) hair is present in the newborn period; they appear as pili
torti at microscopic examination. Typical facies consist of frontal or
occipital bossing, abnormal or absent eyebrows, pudgy cheeks with sagging
jowls, micrognathia, and pallor. Characteristic radiographic changes include
wormian bones in lamboid and sagittal sutures, anterior rib flaring, spur
formation on the femoral and humeral metaphysis, and osteoporosis.
Arteriography shows elongation, tortuosity, narrowing, and dilatation of
cerebral, visceral, and limbs arteries. Gastroesophageal reflux and
recurrent aspiration ...