Thursday, April 21, 2016

Special Interview: Justin Hamilton and his life with CEP~ Congenital Erythropoietic Porphyria

Thank you Justin for participating in this interview. (Congenital Erythropoietic Porphyria)  (CEP))
We take a close look at a day in the life of Justin’s Life with CEP, well also learn what it is and just how rare it really is.  http://www.clinuvel.com/en/skin-science/skin-conditions/rare-skin-conditions/congenital-erythropoietic-porphyria-cep
So at what age did you start experiencing problems?  What were they? 
 When I was first born. They noticed in the hospital my urine was a red fluorescent color. They thought it had something to do with my kidneys. 

Did anyone else in your family have a history of CEP? No 

When and how were you diagnosed?  Where?  When I was 6 months old. They did blood test and cultures. I was diagnosed at the McCook, Nebraska Clinic. (Currently 150 or less reported cases)

Did they get your diagnosis right the first time?  
Yes, besides thinking it was my kidneys. Mom then noticed blisters when the sun would be on me. They then did test to find out I had CEP. 

How do you feel about having CEP the ups and downs?  CEP sucks, I wouldn't wish it on my worst enemy if I had one. The ups to CEP there are not really any at all, other than that it gives you a look at life to strive to be positive, making you a fighter for the things that most people take for granted. The downs are endless and new every day. The fact that you are unable to go outside without being all covered up and drenched in sunscreen. The pain and the scarring that happens from any tiny bit of exposure. Not being able to be "normal" like others that can run around outside and soak up the sun. Growing up and living with CEP people staring at you and giving you mean looks because they are not aware of what really is going on. There are times that I’m down and stressful times. Trying to cope with all that is thrown at you is a daily struggle. 

What are your symptoms?  How have you managed your symptoms? Symptoms are any exposure to the sun or certain lights I get blisters, some big some small. All very painful, and then after they pop they take weeks to heal. Then when they do heal they leave scars that limit normal skin growth. Pain becomes a normal thing that I become used too and just pray it helps fast each time. Trying to manage it is just lots of sunscreen and coverage when in the sun. I believe everything happens for a reason. So I just take what the good lord gave me and make the best of it. 

Have you learned anything from having a rare disease?
CEP HSS taught me to take this disease seriously. I wish I would of been more protected when I was younger age and not been so stubborn when putting on sunscreen, long sleeved shirts, hats and so on. I seem to learn something new every day. 


How have your Doctor’s treated you in the past and present?
 They have treated me with antibiotics for infections from my sores. They have had me use steroid creams for my sores. Really that about it. This disease did attack one of my eyes. Which I now don't have much vision left in. Also caused a small hole in that eye. I see an eye specialist regularly. They put glue in the hole and a contact over to keep it stable. My doctors have been supportive and helpful with everything that comes with it. 

What are your future goals?  Hobbies that you enjoy?
My goals in life are to live as long as I can be watching my Kid’s growing up and spending time with my wife. I try to stay as covered as possible. And take each day like it was my last. I enjoy the outdoors which is hard since that is where I get most of my exposure from. But I live raising crops, animals, hunting, and fishing. My love for race cars keeps me going. 

Do you work and what do you do?
In try to keep busy. Working hard is always been a big part of my family's way of life. I try my best to continue to help family and friends with what I am limited too. I try to help at the farm or the family car dealership when I can. 


Are you Married & do you have children & how has this impacted you in any way? 
I am happily married since 2011, since then we have two beautiful children. A boy Brayden who is 2 1/2 and a girl Brylee who is 1 1/2. They are my reason for living. I love then so much. There are some thing that limit me to my husband and father duties. With my hand’s being so small and sore (my hands are ½ the size of a normal persons due to the severe scaring) it’s hard for me to change diapers, simple stuff like that. I can't play with them outside on a nice day for a very long period of time like I would like to be able too. 

If Holly would like to comment, how do you feel about Justin as a husband and father and how does he handle the CEP daily?  He is an amazing husband and an even more amazing dad. There are some things that limit him. But we are aright with that. I understand and try to help him in every way possible to make things easier on him. He has good days and bad days. He does not shoe to anyone else how much pain he might be in. But when it is just the two of us he is able to open up some more. He is a very positive attitude about it all. Some days he may be in enough pain he stays in bed all day. But the next he is ready to go. The kids and I love him so much. 

What encouragement would you give to others that have CEP and why raise awareness?
All I can say is words of encouragement. Don't take life for granted. Take your disease seriously and take the needed precautions no matter how much it sucks. Keep positive and have faith. There will be good and bad days but how you react to it is your choice. So stay positive and live life to the fullest. It is very important to spread awareness so that other’s may understand. The more people and doctors that know more about it they   can understand to make it easier on me and ways to help. 

If the APF has helped you at any given point, how have they helped you?  
The APF has helped out greatly. The thing I like the most is it brings all fellow porphyrian’s together to tell their stories and help one another to make this disease better to live with. In am very thankful and blessed even with CEP. 

Thank you Justin for sharing your life with CEP! Holly Thank you for raising awareness and your support to your husband and to the American Porphyria Foundation.  For a description of CEP please read below also you can learn more information by contact the APF~ 1-866-APF-3635 or visit porphyriafoundation.org




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Here are the facts of: Congenital erythropoietic porphyria, or CEP, is an extremely rare, inherited metabolic disorder.  It is caused by genetic defects which lead to deficiency of the enzyme uroporphyrinogen III cosynthase (UROS).  The disease is characterized by extreme photosensitivity (abnormal cutaneous reaction to sunlight) which can leave severe scarring, blister formation and the loss of digits or other features. Damaged skin can become infected, leading to further necrosis and deformities. The face, hands and arms are the most significantly affected as they are frequently exposed; sometimes presenting as severe disfiguration.

Incidence

The incidence of CEP is not known, but it is exceedingly rare; as of 2006, there were approximately 150 cases reported worldwide. Onset is usually during the early years of life as the genetic defects are present from birth. A milder form with onset in adulthood has been described in a small number of patients; six individuals as of 1990.

Causes

Congenital erythropoietic porphryia belongs to a family of diseases known as porphyrias. These are characterized by the overproduction and accumulation of chemicals, known as porphyrins, in various tissues within the body. The porphyrias come about due to faults or deficiencies in the pathway which leads to the production of heme (a major component of the hemoglobin in red blood cells).  
CEP is caused by a genetic defect, or mutation, in the UROS gene. This gene encodes an enzyme, uroporphyrinogen III cosynthase, which is essential to the step-wise progression of heam synthesis (see Figure 1). The effect of the mutation is that the enzyme is only marginally active. This means that not only is heam synthesis severely impeded, but also that the pathway takes an alternative route, leading to the build of porphyrins. In the case of CEP, the particular porphyrins in excess are uroporphyrin I and coproporphyrin I.

Figure 1. The Heme Biosynthetic Pathway, illustrating the defect in CEP
While the enzyme’s activity is dramatically reduced in CEP patients, it is not entirely absent as this would likely result in the complete absence of red blood cells and therefore death. The porphyrins are partially excreted in the urine and feces, though a large portion enters into circulation and is deposited in bodily tissues; primarily the bone marrow, skin, blood and teeth. Porphyrin accumulation has toxic effects on the cells in these organs. This accounts for many of the symptoms experienced by CEP patients, including their heightened photosensitivity.
CEP’s rarity is partially due to its pattern of inheritance as a recessive trait. This means that an individual need’s to have two copies of the defective gene - one from their mother and one from their father - in order for the condition to be present. An individual with just one defective gene will be a carrier of the disease but will not exhibit any symptoms, since the properly functioning gene is able to produce intermediate levels of the enzyme. There is typically no family history of CEP and both parents are healthy.
A number of mutations in the UROS gene have been discovered in CEP patients, all cause dysfunction of the UROS enzyme. Of the 35 described, the C73R mutation is the most common, present in about a third of all cases. This particular mutation is associated with a severe form of the disease.

Symptoms

Symptoms of CEP are diverse and can range from mild to severe. Along with cutaneous damage due to enhanced photosensitivity, CEP patients commonly suffer anemia due to the breakdown of red blood cells (hemolysis). The following symptoms may be present to differing extents in individual patients:

Skin

·         Blistering and rashes on light-exposed skin
·         Scarring
·         Increased skin fragility
·         Skin destruction and erosion
·         Abnormal hair growth (hypertrichosis/hirsutism)
·         Loss of eyebrows and eyelashes
·         Mutilation of cartilage structures, such as the ears and nose
·         Loss of digits and facial features
·         Bacterial infection of damaged skin, possibly leading to further necrosis and deformation

Blood and other tissues

·         Anemia due to the breakdown of red blood cells
·         Excessive red blood cell production (erythrocyte hyperplasia)
·         Bone loss, fragility or hardening
·         Enlarged spleen (splenomegaly)
·         Brown, pink or red discoloration in urine, due to the presence of porphyrins
·         Teeth stained red (erythrodontia), also due to accumulation of porphyrins
·         Ocular (eye) lesions

Prenatal

·         Brownish color to the amniotic fluid
·         Accumulation of fluid in the fetus whilst still in utero (hydrops fetalis)
In addition to the physical symptoms, CEP patients often suffer poor mental health. This is due to both the level of pain and discomfort experienced and the psychological impacts of their appearance. These individuals can be stigmatized and often avoid interaction with other people.  Many struggle both socially and professionally, thus CEP has an extreme impact upon patient quality of life.

Diagnosis

CEP is the only porphyria that can be diagnosed prenatally. It is indicated by raised levels of uroporphyrin I in the amniotic fluid as early as 16 weeks in utero. More commonly, diagnosis is in infancy or childhood through a combination of the following methods:
·         History of patient symptoms
·         Quantitative screening using spectrophotometry or fluorimetry is considered the most accurate method of diagnosis. When uroporphyrin I and coporphyrin I are present in blood a plasma spectrofluorimetry is seen at 615-620 nm.
·         Measurement of elevated levels of uroporphyrin I and coproporphyrin I in blood, urine or fecal analyses
·         Examination of the eyes or urine using a Wood’s lamp

Treatment

Total avoidance of sunlight and other sources of visible/UV light (i.e. solariums) is vital to preventing skin damage in CEP. Sun-protective clothing and sunscreen containing the light-blocking compounds zinc oxide or titanium dioxide may offer some protection. Plastic window films and window tinting around the home and in the car can reduce damaging wavelengths of light penetrating the skin. In addition, incandescent light bulbs emit less phototoxic wavelengths of light than fluorescent lights. Physicians recommend CEP patients try to avoid physical injury which may worsen fragile or damaged skin.
CEP treatments can be radical and patient response is varied:
Bone marrow transplantation (BMT) - the only therapy to date that presents a potential cure for CEP. It has proved extremely successful in a handful of patients, however the long-term results of BMT are not yet known. This form of therapy also comes with significant risks, including infectious complications and a high mortality rate. In a few children, BMT has resulted in complete remission of CEP. Improvements included normal hemoglobin, considerably reduced uroporphyrin I in the urine and no skin lesions in spite of unrestricted sun exposure; this is evidence of the best case scenario. Stem cell cord blood transplantation has also been reported effective in a few CEP patients.
Blood transfusions - these decrease the production of red blood cells and hence porphyrins in CEP patients. Transfusions have successfully reduced disease symptoms in several patients, however there are complications associated with chronic transfusions (i.e. iron overload).
Splenectomy - a splenectomy is the surgical removal of the spleen. It can increase the lifespan of red blood cells, reducing anemia.
Oral sorbent medications - these include activated charcoal and cholestyramine which act by binding the excess porphyrins and preventing their absorption. In several patients these have reduced porphyrins in the blood and urine, in one case leading to complete remission. In contrast, there are also several reports of no effect and one of exacerbated condition; thus, caution should be exercised. Further, this treatment may be accompanied by the mild complication of poor nutrient absorption.
Oral beta-carotene - may act as a mild photo protectant to reduce the symptoms of photosensitivity, though treatment usually requires unreasonably large doses. It has been trialed in CEP with minimal efficacy.
Oxygen quenchers - these are oral medications, such as ascorbic acid and alpha-tocopherol, which mop up excess reactive oxygen species to lessen porphyrin-induced photo damage; also only marginally effective.

Prognosis

The prognosis for a CEP patient depends on both the clinical severity of the condition and their response to available treatment. Severity is mainly dependent on the amount of residual activity the UROS enzyme has. Into the future, potential therapies may exist in the form of stem cell transplantation and gene therapy to correct the mutation and produce a functional UROS enzyme.
During puberty, a child’s hemoglobin levels increase to that of an adult. Along with an increase in heam comes a rise in porphyrin levels in CEP patients, therefore increase in symptoms or relapse may occur during adolescence. Where treatment is ineffective, the life expectancy of CEP patients is shortened. 

References

·         American Porphyria Foundation, n.d, Congenital Erythropoietic Porphyria (CEP), accessed 23rd August 2010, <http://porphyriafoundation.com/about-porphyria/types-of-porphyria/CEP>.
·         Canadian Association for Porphyria, n.d, Congenital Erythropoietic Porphyria, accessed 23rd August 2010, (no longer online).
·         Hebel, J.L, 2009, Congenital Erythropoietic Porphyria: Treatment & Medication, eMedicine Specialties, accessed 23rd August 2010, <http://emedicine.medscape.com/article/1103274-treatment>.
·         Hift, R.J, Meissner, P.N & Kirsch, R.E, 1993, ‘The effect of oral activated charcoal on the course of congenital erythropoietic porphyria’, The British Journal of Dermatology, 129(1):14-17.
·         National Organization for Rare Disorders, 2008, Porphyria, Congenital Erythropoietic, accessed 22nd December 2015,<https://rarediseases.org/rare-diseases/porphyria-congenital-erythropoietic/>.
·         Singh, D.K & Rai, R, 2008, ‘Congenital Erythropoietic Porphyria’, Indian Pediatrics, 45:865.
·         Wiederholt, T, 2006, ‘Identification of mutations in the uroporphyrinogen III cosynthase gene in German patients with congenital erythropoietic porphyria’, Physiological Research, 55(suppl. 2):S85-S92.

Online associations

·         American Porphyria Foundation

Online resources

·         GeneBennett.net - A working biography of Gene Bennett and his life experiences with CEP
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