Why you should know about Menkes Disease?

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About Menkes disease

Menkes disease (MNK) is one of the rarest medical conditions that originally reported in 1962 by John Hans Menkes et al. It is a medical disorder that interferes with the adequate distribution of copper in the system thus contributing to copper deficiency. It is an x-linked, autosomal recessive condition that commonly affects males whereas the females can also develop due to the presence of 2 defective alleles. Menkes disease also occurs in milder variants such as occipital horn syndrome which is also referred to as a type-9 Ehlers Danlos syndrome or X-linked cutis laxa.

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Define Menkes disease.

Menkes disease, also referred to as kinky hair disease, is an X-linked recessive disorder that causes copper deficiency in the body. It is a neurodegenerative disorder that impairs the copper transportation thus resulting in an abnormal copper metabolism in the body. It is called as kinky hair syndrome as its features are analogous to that of an Australian sheep's brittle wool that is usually raised in regions with copper deficient soil. According to the medical tests, the condition basically presents with abnormally low serum copper and ceruloplasmin levels in the body.

What are the other names for the Menkes disease?

The other names for Menkes disease (MNK) include: Menkes syndrome, steely hair disease, copper transport disease, Menkes kinky hair syndrome or kinky hair disease.

What causes Menkes disease?

In general, Menkes syndrome is an inherited condition that follows an X-linked recessive trait. Menkes disease is basically caused by a genetic mutation of the ATP7A gene that is situated on the chromosome Xq12-q13. This results in the poor copper distribution to the body cells and abnormal copper accumulation in various organs and tissues. Kidneys and small intestine present with high copper accumulation whereas the brain including other tissues display abnormally low copper levels. Thus, abnormally low copper levels can directly impair the normal function of various copper containing enzymes (like lysyl oxidase) that play a significant role in maintaining the normal function and structure of various tissues such as skin, bone, blood vessels, hair, and the nervous system.

What are the Signs and Symptoms of Menkes disease?

Menkes disease is mainly characterized by growth failure, degenerated nervous system, hair that is sparse and coarse. The early onset of the disorder is basically during infancy. Some of the common signs and symptoms of MNK disorder includes sagging facial features, weak muscle tone (hypotonia), mental retardation, seizures, and delayed development. The affected patient develops weak bones (osteoporosis) thus resulting in fracture.

The patient presents with coarse, brittle hair and widened metaphysis. Rarely, MNK symptoms can be less severe when developed during late childhood. MNK affected newborns are premature, with the early onset of symptoms. Affected infants experience an abnormal copper absorption in the intestines thus leading to a secondary deficiency in especially, the mitochondrial enzymes that are copper dependent. Initially, the growth phase may be normal or slightly slowed for a duration ranging from 2 to 3 months, followed by a severe growth delay accompanied with early impaired neurological skills.

An affected patient can also develop seizures, subnormal body temperature, failure to thrive, and strikingly peculiar hair features that appear colorless or steel-colored, kinky, and can break easily. The gray matter of the brain is affected by an extensive neuro-degeneration. The blood vessels of brain can be twisted with the broken and frayed inner walls often resulting in the arterial rupture or blockage.

Some of the common physical findings caused by the Menkes disease include:

Abnormal looking eyebrows, eyelashes and a characteristic kinky hair

An infant with classic Menkes disease has a lusterless, de-pigmented hair with pili torti and the eczema affected skin looks pale.

The hair looks short, coarse, sparser, twisted both at the back and sides, often with abnormal or light pigmentation that appears either silver, white, or gray (it can also grow along with black hair or can be brown or blonde depending upon the ethnic race)

Some of the abnormal facial features of menkes disease include:

Sunken or depressed nasal bridge

Sagging cheeks and ears with Jowly

High arched palate

Delayed eruption of teeth

Some of the abnormalities associated with progressive cerebral degeneration include:

Seizures

Loss of growth milestones

Instability to temperature

Profound truncal hypotonia accompanied with appendicular hypertonia

Some of the ocular manifestations include:

Visual imbalance

Ptosis (drooping of the upper eyelid)

Diminished pupillary response to light with pallor of the optic disc

Iris hypopigmentation and hypoplasia

The Connective-tissue manifestations include:

Joint hypermobility

Loose skin over the trunk and nape of the neck

Development of multiple Polypoid masses in the gastrointestinal tract

Bilateral inguinal and umbilical hernias

Diverticulated Bladder with dilated ureters

Emphysema

Vascular manifestations of MNK disease include:

Arterial aneurysms of the lumbar, Brachial, and iliac blood vessels including arterial rupture

Thrombosis

Internal jugular vein aneurysms

Pulmonary artery hypoplasia

Skeletal manifestations include:

Osteoporosis

Multiple congenital deformities and fractures

Short clavicles with characteristic, hammer-shaped distal ends

Metaphyseal widening and spurring

Flared, radial and ulnar metaphyses

Periosteal deformity of the Diaphyses

Scalloping, posterior part of the vertebral bodies

Wormian bones

Pectus excavatum

Renal calculi and

Bleeding diathesis

The MNK patients affected by an occipital horn syndrome can have extensive manifestations of the bone and connective tissues. Occipital horn syndrome is a mild variety of MNK disease that develops during mid-childhood and it is also referred to as Ehlers-Danlos type 9 or X-linked cutis laxa. It is associated with loose skin, deformed joints, coarse hair and calcium calcifications at the skull base.

They present with easily, bruisable and hyperelastic skin; lax skin; hernias; hyperextensible joints; bladder diverticula; and multiple skeletal deformities like occipital horns (exostoses), occipital tendinous with wedge-shaped calcifications especially at the insertion between sternocleidomastoid and trapezius muscles. Although, occipital horns may not develop during early developmental stage, affected patients can present with autonomic dysfunction and mild mental retardation. Unlike MNK disease, these patients develop moderately low levels of serum copper and ceruloplasmin. Cultured fibroblast cells moderately accumulate copper unlike MNK.

Other varieties of mild Menkes disease usually present with mild mental retardation and ataxia.

References: http://en.wikipedia.org/wiki/Menkes_disease

http://emedicine.medscape.com/article/1180460-clinical#a0217

http://rarediseases.about.com/cs/menkesdisease/a/022704.htm

http://www.ninds.nih.gov/disorders/menkes/menkes.htm

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Dr Chaitra S's picture
Author: Dr Chaitra S

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