Menkes disease

Menkes disease, also known as trichopoliodystrophy or kinky hair kinky vessel syndrome, is an X-linked recessive disorder that results in a derangement in copper handling. It results in low copper levels and subsequently, deficiency in copper-dependent mitochondrial enzymes. 

Epidemiology

Menkes disease is rare, occurring in 1 case per 300,000 population.

Clinical presentation

Signs and symptoms typically appear in infancy. Hair may be fine, silvery and brittle (kinky hair) and connective tissue disturbances lead to loose skin.

There is progressive neurologic deterioration: seizures usually begin in the first few days or months of life with progressive hypotonia and developmental delay in the first year of life.

Other features include pectus excavatum, failure to thrive/gain weight, and urinary bladder diverticula ⁸. 

Pathology

Genetics

Menkes disease is a multisystem disorder with an X-linked recessive inheritance, caused by mutation of the gene ATP7A located on Xq13.3. This gene encodes a copper-transporting ATPase that transports copper into cells. The mutated gene cannot encode this transporter protein, leading to copper deficiency in the body. Since mitochondrial enzymes (such as cytochrome c oxydaze) contain copper ions, lack of copper leads to mitochondrial dysfunction. Two-thirds of patients have a positive family history, while the other one-third of patients have spontaneous mutations.

Radiographic features

Musculoskeletal manifestations

• metaphyseal widening of the femur and ribs

• tibial and femoral spurs

• Wormian bones

CNS manifestations

Brain manifestations of Menkes syndrome are progressive cerebral and cerebellar atrophy, elongated and tortuous intracranial vessels as well as bilateral subdural collections or bleeds.

MRI

At birth, the brain often appears normal on MR images.

During the course of the disease, however, rapidly developing cerebral and cerebellar atrophy and prominent white matter changes can occur ⁴.

• T1: can show hyperintensity of the basal ganglia similar to that of chronic hepatic encephalopathy

• MRA: cerebral vessels usually are tortuous and elongated on MR angiograms ^4-6

Chronic bilateral subdural haematomas also may be visualised.

Treatment and prognosis

The condition is lethal and affected males typically die by age 2-3 years. Pneumonia or respiratory infection is the usual cause of death. Treatment is mainly supportive.

History and etymology

Menkes disease is named after the American physician John H Menkes (1928-2008) ⁷.

Differential diagnosis

Menkes disease may mimic non-accidental injury (NAI) with retinal haemorrhage and bilateral subdural haematomas. Hence, prudence is advised in always ruling out NAI, particularly when other intracranial signs of Menkes disease are not seen. In a similar manner, the differential diagnosis also includes glutaric aciduria.

See also

• occipital horn syndrome