Menkes Syndrome

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 Malabsorption; Trichopoliodystrophy.

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 ...