Harlequin Ichthyosis

By: Dan Hood, Matt Sharbaugh, Brian Monterroso

WARNING!

• THE IMAGES YOU ARE ABOUT TO SEE ARE REAL AND MAY CAUSE SOME TO BECOME QUEASY !

Biological Basis

• Intro:– Harlequin Ichthyosis,

most commonly known as harlequin’s disease or HI is the most sever form of keratinizing disorders.

– The condition is characterized by a profound thickening of the external layer of the skin.

The Condition

• This rare but debilitating condition occurs in 1 in 300,000 births.

• The babies are born with a massive hard shell like covering containing many deep fissures.

• The babies also have problems contracting their eyes, mouths, and appendages.

• They have a hard time moving because where there are folds on a normal baby there are cracks on an HI child.

The Condition Continued

• In most cases the child is born prematurely.• Most of the time the child dies within a few days

because of respiratory disease, bacterial infections, feeding difficulties, and body temperature regulation.

• Respiratory failure can result from restricted movement of the chest muscles, and bacterial infections occur from the lack of a protective outer layer. The bacteria can easily enter the baby through the fissures in the skin. The cracks in the skin allow water and heat to escape.

Surviving HI• With improved neonatal

care more HI children have the chance of survival.

• The few survivors have skin that turns dark red and very scaly.

• The skin will eventually from a scaly layer and dry out so water retention and sun protection are concerns for the survivors.

Detection • One way to notice the

child has abnormalities is through a sonograph during the second trimester.

• The sonograph shows abnormal facial features and small foot size in ratio to the femur.

• A fetal skin biopsy can be done but it is an invasive procedure. From the biopsy, tests can be run on the child’s genes to see if they are abnormal.

Genetics

• HI is caused by a frame shift mutation or a large deletion.

• The gene effected is the ABCA12 in the 2q35 region, which is involved in lipid transport that impacts the development of the epidermis.

Genetics

• The condition is inherited autosomal recessively.• This means an effected individual must have two

copies of the gene on chromosome 2 to have the disorder.

• People with only one copy of the normal ABCA12 gene are not effected by the disorder.

• The disorder does not show prevalence in gender or racial background.

• There have been many cases of HI in southern Iraq where mothers were exposed to uranium oxide during the early stages of pregnancy.

Lipid Transport

• Members of the class of ABCA genes are involved in lipid transport across cell membranes. The proteins the gene produces bind to ATP for active transport of lipids to the stratum corneum, the outer most layer of the skin. These lipids are important for the protection of the skin.

Lipid Transport

Treatment

• The treatment of HI babies is quite extensive.• The vitals of an HI baby must be constantly

monitored.• Their eyes must be constantly kept moist and

shielded from the sun.• The environment they live in must be constantly

kept sterile to protect from infection.• They must have a salt solution applied followed

by a lubricant to facilitate the skin cells to fall off and to keep the cells moist.

• Antibacterial pills and creams are also used to fight infection.

Ryan Gonzalez

• Almost all HI children die in infancy but there are exceptions.

Birth

• He was born with harlequin ichthyosis.

• Dr. Brian Saunders, a neo-natologist, cared for Ryan during the first critical moments of life.

• Ryan’s skin was so tight that it was crushing his lungs.

• Accutane, a vitamin A derivative, was used to keep the skin from hardening.

• His scales became smaller and thinner.

Life of a Harlequin

• He competes in triathlons.• To keep his skin from

hardening, he covers himself in lotion 7 times per day.

• He has to consume 7,500 calories per day.

• He tube feeds himself pure protein every night while he sleeps to help him produce extra skin cells.

The View• The condition was first described in South Carolina by Reverend

Oliver Hart.• "On Thursday, April ye 5, 1750, I went to see a most deplorable

object of a child, born the night before of one Mary Evans in ‘Chas’town. It was surprising to all who beheld it, and I scarcely know how to describe it. The skin was dry and hard and seemed to be cracked in many places, somewhat resembling the scales of a fish. The mouth was large and round and open. It had no external nose, but two holes where the nose should have been. The eyes appeared to be lumps of coagulated blood, turned out, about the bigness of a plum, ghastly to behold. It had no external ears, but holes where the ears should be. The hands and feet appeared to be swollen, were cramped up and felt quite hard. The back part of the head was much open. It made a strange kind of noise, very low, which I cannot describe. It lived about forty-eight hours and was alive when I saw it."

Live or Die?

• Two doctors in the Netherlands have developed a checklist to determine whether a newborn is suffering greatly or not.

• If the doctors find that the child is suffering greatly, they support euthanasia (assisted suicide).– “Our society has gone off the edge in terms of

protecting the vulnerable by forcing them to suffer.”–Glen McGee

References• http://ghr.nlm.nih.gov/condition=harlequinichthyosis#statistics• http://www.asylumeclectica.com/malady/archives/harlequin.htm• http://www.10news.com/health/3919722/detail.html• http://dermatology.wustl.edu/dermsub/caseofmonth/7-2000a.html• http://www.scalyskin.org/content.cfm?ContentID=222&ColumnID=6• http://www.jultrasoundmed.org/cgi/content/full/23/12/1653• http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1199369• http://www.bbc.co.uk/dna/h2g2/A3816830• http://www.jci.org/content/vol115/issue7/images/large/

JCI0525736.f1.jpeg• http://ribosome.med.miyazaki-u.ac.jp/RPDB/Map/RPL37A.gif• http://www.answers.com/topic/harlequin-type-ichthyosis• Chan, Y et. All. “Harlequin Ichthyosis in Association with

Hypothyroidism and Juvenile Rheumatoid Arthritis.” Pediatric Dermatology. Vol 20. No. 5. p. 421-426. 2003.