Menkes Disease

The signs and symptoms of Menkes disease can vary. At birth, cephalohematomas (i.e., blood accumulation underneath the scalp) and spontaneous fractures may occur. Infants may present with jaundice, temperature instability, hypoglycemia, hernias (e.g., umbilical, inguinal), loose and pale skin, and failure to thrive. Connective tissue defects and bone abnormalities (e.g., pectus excavatum, pectus carinatum, frontal bossing, micrognathia, long arched palate) are common, leading to multiple fractures and tortuous blood vessels that cause fluctuating blood supply. Hair is normal at birth but is replaced by fine, sparse, kinky, wiry, or steel wool-like hair (i.e., pili torti) over time. This gives Menkes disease its colloquial name, “kinky hair disease.” 

The less severe form of Menkes disease, occipital horn syndrome, primarily affects connective tissue. In this form, skeletal abnormalities such as kyphosis, scoliosis, pectus excavatum, and pectus carinatum are common. Individuals may also have hypermobility of their joints, vascular abnormalities (e.g., aneurysms, varicose veins, orthostatic hypotension), urogenital abnormalities (e.g., bladder diverticula, urinary tract infections), and low intellectual aptitude. OHS has characteristic facial features including a long, thin face; down-slanting eyes; long philtrum; large ears; and loose skin. Their life expectancy varies from early childhood to 50 years of age.

In the more severe type of Menkes disease, infants may progress through normal psychomotor development for the first 2 to 4 months before neurologic regression begins. They may then experience unrelenting seizures despite treatment, drowsiness, lethargy, spasticity, weakness, and joint hypermobility.  At later stages, vascular abnormalities may occur (e.g., aneurysms, subdural hematoma), as well as anemia, blindness, and respiratory failure. Death typically occurs within the first three years of life due to cerebral hemorrhage or neurodegeneration.

Menkes disease may be suspected after a thorough history and physical examination by a healthcare professional. A physical examination may reveal the characteristic clinical features. Once a clinical assessment has been made, a healthcare professional may order serum copper levels and ceruloplasmin levels, which are typically low in Menkes disease. However, these blood tests may not be accurate in neonates, therefore, plasma catecholamine concentrations may be assessed instead, as copper is essential to their enzymatic processes. High ratios of the initial substrate compared to the end product may indicate reduced enzyme activity. For example, high DOPA (i.e., the initial substrate) to dihydroxyphenylglycol (i.e., the end product) displays low dopamine β-hydroxalase enzyme activity indicative of a disruption in the enzymatic process due to Menkes disease. Genetic testing may also be completed, indicating a mutation to the ATP7A gene.

In addition to diagnosing Menkes disease, it is important to assess for concomitant pathologies. A cystourethrogram may be useful in identifying urogenital abnormalities. Vascular studies can be used to diagnose aneurysms. X-ray or CT imaging studies may show osteoporosis, fractures, or cranial Wormian bones. In OHS, radiographic studies might show occipital bone protrusions that mimic horns. A light microscopy hair analysis can also show characteristics of Menkes disease.

Menkes disease has no definitive, curative treatment, therefore, treatment focuses on symptomatic care and treating coexistent disease processes to improve survival and quality of life. Vascular complications such as aneurysms may be treated with conservative management, and if unstable, clipping or endovascular coiling may be necessary. Physical therapy and pain medication (e.g., acetaminophen, ibuprofen) may be used for skeletal abnormalities.