Friday, October 31, 2014

5 Tips to 'Fall Back' From Daylight Saving Time 2014

5 Tips to 'Fall Back' From Daylight Saving Time 2014

UTO START: ON OFF
What's better than sleeping in on a Sunday? How about dodging the days-long consequences of rolling the clocks back this weekend?
Daylight Saving Time ends this weekend, which means that most residents in the country return to Standard Time at 2 a.m. Sunday. To do so, most people set the clocks back one hour Saturday night, before they hit the hay. This does not apply to you if you live in most of Arizona or Hawaii, where it’s always island time.
Sure, you'll gain an hour when Daylight Saving Time ends at 2 a.m. Sunday. But spending said hour in bed after sunrise will do you few favors in the long run, sleep experts say.
"It will hit you Sunday evening," said Dr. Yosef Krespi, director of the New York Head and Neck Institute's Center for Sleep Disorders. "But if your body clock is tuned to waking up with sunlight, you're going to benefit."
The body clock is a cluster of neurons deep inside the brain that generates the circadian rhythm, also known as the sleep-wake cycle. The cycle spans roughly 24 hours, but it's not precise.
"It needs a signal every day to reset it," said Dr. Alfred Lewy, director of Oregon Health and Science University's Sleep and Mood Disorders Laboratory in Portland.
The signal is sunlight, which shines in through the eyes and "corrects the cycle from approximately 24 hours to precisely 24 hours," said Lewy. But when the sleep-wake and light-dark cycles don't line up, people can feel out-of-sync, tired and grumpy.
With time, the body clock adjusts on its own. But here are a few ways to help it along.
1. Wake Up at a Normal Time Sunday Morning
Many people see the extra hour as an excuse to stay up later and sleep in longer. But sleeping through the Sunday morning sunlight can leave you feeling out of sorts for the start of the week, according to Krespi.
Instead, try to get up at the same time. Use the extra hour to go for a morning walk or make a hearty breakfast.
2. Eat Well and Exercise
Speaking of morning walks and breakfast, an active lifestyle and a healthy diet can work wonders for your sleep, according to Krespi. So grab your partner, your dog or your favorite playlist and get outside some fresh air and exercise. And dig into a breakfast packed with whole grains and protein to keep you energized through the 25-hour day.
3. Get a Good Night's Sleep Sunday Night
Still have extra time to kill Sunday? Use it to turn your bedroom into a full-fledged sleep zone.
"It has to be quiet, it has to be cool and it has to be dark," said Krespi. "Shut down your gadgets and turn away that alarm clock so you don't watch it tick."
Try to hit the sack at your usual bedtime, even though it will be dark one hour earlier.
4. Try a Low Dose of Melatonin
While light synchronizes the body clock in the morning, the hormone melatonin updates it at night. The exact function of the hormone, produced by the pea-size pineal gland in the middle of the brain, is unclear. But it can activate melatonin receptors on the neurons of the body clock, acting as a "chemical signal for darkness," Lewy said.
5. Know That Your Body Will Adjust It might take a few days to feel 100 percent normal, but fear not: Your body will adjust to the new light-dark cycle.
"Some people suffer more, some people less, it all depends," said Krespi, adding that falling back in November tends to be easier than springing forward in March. "On Monday morning, we'll appreciate that we're waking up for work or school with sunlight."
ABC News' Colleen Curry contributed to this report.


"Remember.....Research is the key to your cure!"

History of Porphyria

History of Porphyria


A Little Bit of History
      1841 The term ‘porphyrin comes from the Greek word, porphyus, meaning reddish-purple. It was first thought that the reddish color of blood was from iron. One early scientist performed an experiment to prove that this was not the case. He washed dried blood with concentrated sulfuric acid to free the iron. He then treated it with alcohol and the resulting iron free residue took on a reddish purple color though it contained no iron compound
     1844 - Gerardus Johannes Mulder determined the chemical composition of this purplish, iron free substance, which he named "hematin,"   He also illustrated that hematin took up oxygen.
     1867 - J.L.W. Thudichum described the beautiful spectrum and fluorescence of these red porphyrins after he published his first book on the analysis of urine.
     1871 - Felix Hoppe-Seyler crystallized hematin and described it’s spectrum.  He then demonstrated that the crystalline form differed from one animal species to another. Using his own newly constructed gas pump, he found that oxygen formed a loose, dissociable compound with hemoglobin, which he called "oxyhemoglobin."  He renamed the iron free hematin ‘hematoPorphyrin’.
     1874 - Dr. J.H. Schultz described a case of a 33-year-old male weaver who suffered from skin sensitivity, an enlarged spleen and reddish urine since he was an infant. He called the condition pempigus leprosus.  His was most likely the first description of protoporphyria. Dr. Schultz was later credited with giving the disease it’s name.
     1880- MacMunn described a patient’s dark reddish urine of a patient with symptoms of an attack of acute Porphyria.
     1888  Shortly after, sulphonal was introduced as a hypnotic drug, Joseph Stokvis had a patient who, after taking the drug, excreated the tell-tale dark reddish urine typical of porphyria.  The elderly woman then became paralyzed and died. Stokvis deducted that the pigment in her urine was the hematoporphyrin.
     1889 - B.J.Stokvis published the first case and clinical description of acute hepatic porphyria.
     1890 - George Harley (1829-96) studied a 27-year-old who also excreted reddish urine and an "unusual nerve disturbance after taking sulphonal. 
     1898 - T.McCall Anderson described two brothers had eruptions with burning and pruitus on the sun exposed areas of their skin so severe that they lost part of their ears and nose.  They exhibited dark urine. 
     1898 - Alfred F. Harris demonstrated that the urine of both brothers contained  the hematoporphyrin group.
     1906 - Dr. Max Dobrschansky described the first case of acute porphyria after a patient had a barbiturate.
     1911 - H. Gunther classified the diseases of porphyria, including congenital erythropoietic porphyria (CEP), which he called congenital hepatoporphyria, the rarest porphyria.
      1913 - Dr. Friedrich Meyer Betz injected himself with hematoporphyrins to determine their photodynamic impact . He subjected himself to the sun and became so photosensitized that the extremely painful photosensitive effect lasted several months. The photos of Dr. Betz taken hours after he injected himself illustrated his badly swollen face.  He was unrecognizable until the swelling decreased.  The-experiment is used today in dermatology text books.  View these photos on the APF website.
     1915 - Hans Fischer studied one of H. Gunther’s patients, Mr. Petry, who had the rare type of Porphyria, CEP. Using data from Mr. Petry’s case, Fischer provided significant insight into the chemistry of porphyrins. He also found that uroporphyrins and coproporphyrins were different from hematoporphyrins and subsequently suggested that the hemato prefix be dropped.
     1923 - A. E. Garrod credits H. Gunther with first recognizing that hematoporphyria was, in fact, an inherited metabolic problem in his manuscript, Inborn Errors of Metabolism. This is the first time the term "inborn errors" of metabolism had been ever used for a group of inherited metabolic disorders and the year CEP was first identified.
     1937 Dr. Jan G. Waldenstrom suggested that the name of the diseases of porphyrin metablolism be porphyrias rather than Hematoporphyrias. Using Paul Ehrlich’s  aldehyde reagent, Waldenstorm identified 103 patients with acute porphyria by testing their urine and noting the red color.  He discovered that asymptomatic family members of these patients also had the same reaction if they ingested even small amounts of barbiturates and sulphonal.
     1949 -Dr. Cecil J. Watson identified cases in which there were excessive amounts of coproporphyrins in the stool and urine and suggested that this was caused by an inborn error of metabolism. He continued his research in the United States, where he and Dr. Samuel Schwartz discovered a fundamental test, , the "Watson-Schwartz tests".
     1954 - R. Schmid, Samuel Schwartz and Cecil. J. Watson classified the porphyrias according to the porphyrin content in the bone marrow and liver.
     1955 - A. Goldberg and H. Berger showed that individuals with an excess of coproporphyrin had another inherited form of porphyria that they called hereditary coproporphyria.  HCP is an autosomal dominant form of hepatic porphyria that is very similar to acute intermittent porphyria, except that some patients develop skin photosensitivity, too.
     1960's – Earnest Porphyria research in Europe and US.
     1961 - Heinrich Gustav Magnus described erythropoietic protoporphyria (EPP) as a genetic disorder arising from impaired activity of ferrochelatase, which is what adds iron to protoporphyrin to form heme.
     1970-2011 - Drs. Anderson, Desnick, Bissell, Bloomer, Bonkovsky,, Bottomley, Dailey, Galbraith, ,Kappas, Kreimer-Birnbaum, Kushner, Lamon, Levere, Levine, Mathews-Roth, McDonaugh, Nichols, Peters, Sinclair, Pimstone, Pierach, Poh-Fitzpatrick, Sassa, Shedlofsky, Schmid, Sassa, Tishler, Tschudy, Watson,,  Phillips and many others too numerous to name have furthered porphyria research and have bettered the health care of all of us with Porphyria. We owe all these people a great debt and a great measure of thanks.
     2008-2011- The APF Protect the Future program to train the next generation of experts was initiated.  We are grateful for the newest experts;  Drs. Manisha Balwani, Lawrence Lui, Gagen Sood, Manish Thapar, Bradley Freilich, Charles Lourenco, Brenden McGuire, Bruce Wang, Majid Rizk, Guiherme Perini, Jennifer Guy, Jeffery Wickliffe,, Aswani Singal, Sajid Mittal,Charles Parker.

King George III and Porphyria

Some historians have speculated that King George III of England suffered from Variegate Porphyria. According to notes made by the physicians attending him at that time, he suffered symptoms similar to those seen in an acute attack of porphyria: abdominal pain, constipation, rashes, confusion and severe weakness in his limbs. They also mentioned that he had dark reddish urine during these sieges and that he was often "mad." The royal physicians were not permitted to conduct extensive physical examinations, so they had to depend on what King George told them about his condition.
On one occasion when he was having a relapse of his mental and physical symptoms, Parliament debated his ability to maintain his position as King. Interestingly, he spontaneously recovered. Since George III ruled during the American Revolution, he was thought to have had a significant impact on Britian's loss to the revolutionaries. His mental and physical lapses were blamed for much of the mishandling of the war. In 1811, George suffered a severe relapse and subsequently was dethroned by the Prince of Wales.
After researching the physicians' reports, Drs. Ida Macalpine and Richard Hunter proposed that King George might have had one of the acute porphyrias. They published their theory in theBritish Medical Journal in 1966 and later wrote a book, George III and the Mad Business, which presented more detailed accounts of King George's malady. It is important to note that a number of Porphyria specialists and other physicians disagree with their theory. However, over the years it has been widely publicized.

Porphyria in Turkey

In southeastern Turkey, between 1956 and 1961, there were reports of an epidemic of PCT. Apparently, in 1954 the Turkish government distributed a supply of wheat seed that had been treated with fungicides containing 10% hexachlorobenzene (HCB). The wheat was originally intended for planting, but the shipment arrived too late in the season. Because there was a limited food supply in the Turkish provinces of Dijarbakir, Mardin, and Urfa, the seed was diverted for food production. It was difficult to quantify the extent and duration of HCB exposure from existing surveys, because the HCB-treated seed appeared no different from untreated supplies.
As many as 5000 individuals were reported to have been affected by the HCB treated seeds. They exhibited PCT-like syndromes as early as 1956. The government discontinued using the HCB-containing fungicide in 1959, but it was not until around 1961 that the PCT outbreak waned. Researchers from clinics near the area began to trace the dietary histories of the affected individuals and discovered that HCB appeared to be the cause of the acquired form of PCT.
Prior to this time, acquired Porphyria associated with exposure to environmental toxins was observed in experimental animal models but only rarely in humans. Shortly after the reports from Turkey were published, the association between the chronic administration of HCB to induce excessive porphyrin accumulation was confirmed in animal models as well.
Although quantitative reports of HCB exposure from Turkey are incomplete, some accounts estimate that the amount of HCB ingested by the affected individuals ranged from 0.05 to 0.2 g/d over an unknown, but "relatively long period," before changes in their skin became evident. Long-term follow-up studies by Drs. Cripp and Peters and their colleagues at the University of Wisconsin indicated that the average lag time between HCB ingestion and clinical manifestation of disease was about six months. Furthermore, their study indicated that the levels of excreted porphyrins did not correlate with the individual's age at exposure, sex, serum HCB levels, or severity of initial symptoms.

Upcoming Patient Meetings & Giving Made Simple

Upcoming Patient Meetings

We invite you, your friends and families to participate in a patient education meeting. The meeting will be held at the Carrie Hall at the Brigham and Women's Hospital on November 9, from 3 pm to 6 pm.
This meeting provides an excellent opportunity for you to speak to the experts and to meet fellow-patients. Please let us know if you would like to participate.
The meeting in San Francisco will be held at the Hyatt Regency Five Embarcadero Center on December 7, from 4 pm to 6 pm. Everyone is welcome to participate.
Please RSVP:  1.866.APF.3635  or  Email:   

Giving Made Simple

We are introducing our new Donations System that helps make it easier for making donations to the APF.  You can now give via text donation or online giving.
Text Donations using  your Smart Phone:
Simply text the amount you wish to donate to 281-730-8161.
Example: $5 or 5= $5.00, $10 or 10 =$10.00, etc. Choose any $ amount you wish to donate.
You will then be sent a link for a one time registration for text donations.
Once you've registered then your future donations are completed by simply texting the chosen giving amount to 281-730-8161.
You should receive a text confirmation that your donation has been received.
 On-Line Giving:
Our new on-line giving is very convenient and allows you to choose what you would like to apply your donation to.
 Example: In Memory of someone, In Honor of someone, Apply it to the PTF (protect the future program), etc...
Just enter the amount you would like to donate and click the go button.
You then have the option of donating as a guest or register and make it easier for future donations.
You should receive an email confirmation that your donation has been received.




"Remember.....Research is the key to your cure!"

Wednesday, October 29, 2014

A 6-month Natural History Study of Acute Porphyrias

A 6-month Natural History Study of Acute Porphyrias

Researchers are currently accepting participants for a 6-month Natural History Study of Acute Porphyrias

Alnylam Pharmaceuticals, Inc. is conducting a natural history study in collaboration with investigators from the American Porphyria Consortium to learn more about the symptoms and the treatment of patients with Acute Porphyrias. You may qualify to participate in this study if you have the diagnosis of acute intermittent porphyria, variegate porphyria or hereditary coproporhyria and have experienced at least 3 acute attacks in the last 12 months or have used Panhematin® or other medicines to prevent attacks. This study will not require you to change any current medication(s) nor require you to If you take part in this study, it will greatly help clinicians and researchers to understand more about porphyria. You will receive study-related medical care and monitoring.
This study will help to learn information about porphyria that could be important in the development of new therapies for patients with Acute Porhyrias.
Please contact us to get involved in the study: 713.266.9617 ornatalia@porphyriafoundation.org


"Remember....Research is the key to your cure!"

Monday, October 27, 2014

Exciting News for EPP Treatment

Exciting News for EPP Treatment

Exciting news!!! The EMA has recommended granting a marketing authorization under exceptional circumstances for Scenesse (Afamelanotide) for the treatment of erythropoietic protoporphyria (EPP). Scenesse is the first medicine for patients with this condition. We believe the FDA will approve it soon. Thanks to the Porphyria Research Consortium Experts: Karl Anderson, MD, FACP, Herbert Bonkovsky, MD, Montgomery Bissell, MD, Joseph Bloomer, MD, Robert Desnick, PhD, MD and John Phillips, PhD, and to all the research volunteers. You are all Medical Heroes! Thanks to the APF stuff as well.

"Remember....Research is the key to your cure!"

Monday, October 20, 2014

Chronic Illness

Sensitivity & specificity of tests for Porphyria

Sensitivity & specificity of tests for Porphyria

Sensitivity is a feature of many of the diagnostic tests for porphyrias, especially when they are done at or near the time of symptoms. Tests that are sensitive for diagnosis of active porphyrias are almost always abnormal when symptoms of Porphyria are present. But the tests vary in specificity, meaning that some of the tests (those with lower specificity) are abnormal in other diseases.
In choosing a test to screen for a disease that is not only uncommon but also causes symptoms that mimic more common diseases, it is obviously important to choose a test that is both sensitive and specific. Fortunately, some tests for Porphyria have both of these features. With such tests, it should always be possible to determine if symptoms might be due to one of the porphyrias.

Table 1. Diseases due to deficiencies of specific enzymes of the heme biosynthetic pathway

The enzymes and their intermediates (substrates and products) are shown in sequence. Some intermediates are porphyrinogens (reduced porphyrins); these are excreted and measured mostly as oxidized porphyrins (click on any of the yellow-highlighted enzyme names to determine if the substances should be measured in blood, urine or feces). A deficiency of the first enzyme, ALAS, causes a type of anemia rather than a Porphyria. (Uroporphyrinogen I synthase is an obsolete term for PBGD and is not shown in the Table.)
Porphyria should be suspected quite frequently, because the symptoms that suggest the diagnosis are common. If a diagnosis of Porphyria is not made promptly, serious consequences to the patient may follow. But more often than not, laboratory testing will show that the patient does not have Porphyria, because other diseases with symptoms that mimic Porphyria are much more common. An effective approach to laboratory testing is one that does not often miss the diagnosis and also does not often incorrectly suggest that Porphyria is present.

"Remember....Research is the key to your cure!"

Wednesday, October 15, 2014

How Can I Deal With Stress?

How much stress are you under?
  • Stress? I don’t even know what that is
  • I can handle it
  • I’m at my limit
  • I’m drowning in stress
HANDLING stress is like pulling a heavy shipping container. A large truck can haul it across the country with ease. But a car cannot. Pulling such a load even a short distance could ruin a car’s engine. The same could be true of your “engine” if you’re overwhelmed with stress.
Is the situation hopeless? Not at all! To keep from burning out, you’ll need either to lighten your load or to get a more powerful “engine.” Actually, you can do both. Let’s see how.

Lighten Your Load

THE CHALLENGE: Overscheduling.

“Someone will ask me to help out with something or to socialize when I really have things that I need to do. I just don’t want to let anyone down.”—Karina. *

THE REMEDY: Learn to say no.

 Modesty, or accepting your limitations, empowers you to say no when the load will be too heavy for you to carry.
Of course, saying no isn’t always an option—for example, when your parents remind you about your chores! But if you let everyone add to your load, you’ll eventually give out. Even the biggest trucks have a load limit.
Tip: If it’s hard for you to turn down someone outright, try saying, “Let me get back to you.” Then, before giving a definite reply, ask yourself, ‘Can I really afford to invest the time and energy needed for this activity?’

 THE CHALLENGE: Procrastination.

“If a task seems difficult, I’ll put it off. But then I’ll worry about the fact that I still have to do it. When I finally start on it, I have to rush, which stresses me out.”—Serena.

THE REMEDY: Get started—even if you don’t finish now.

 Confronting a hard task is bad enough, so why add to the load by procrastinating? That just keeps it before you longer!
To create incentive, make a to-do list. Break down big tasks into manageable sizes. “I love lists,” says a young woman named Carol. “Usually I put the things I dislike the most first, and then as I check them off, it gets easier. Before you know it, you can move on to the things in your life that are more fun!”
 Tip: If you struggle to get started on a task, set a timer for 10 or 15 minutes and begin working on it right away. When the alarm goes off, you’ll have 10 or 15 minutes of the job completed. Now that you’ve started, you might be surprised at how much easier it is to do more on the task.
Cut out the clutter! When you have to rifle through chaos to find your homework or clean clothes to wear, you raise your stress level. For a less hectic morning, set aside five minutes to tidy up before going to bed

Get a More Powerful “Engine”

Make sure your “engine” can handle your load

Take care of your body.

Experts agree that a healthful diet, regular exercise, and proper sleep will help you to get more done. *Don’t worry—taking care of your body isn’t all that complicated. A few simple steps will get you started. Take sleep, for example. Try the following.
  1. Get enough sleep. Set regular times to go to bed and to get up, at least on school days and workdays.
  2. Allow yourself enough time to unwind. Don’t exercise within three hours before going to bed, and avoid heavy snacks and caffeine as bedtime nears.
  3. When it’s time to go to bed, try to make your bedroom dark, quiet, and comfortable.

Connect with others.

Don’t hesitate to turn to your parents and friends for assistance. Will that really help? Yes, for studies show that emotional support reduces the damage that increased stress can cause to your heart, blood vessels, and immune system.   When “anxious care” weighs you down, true friends can offer you a “good word” of encouragement, which may be just what you need to make it through.

"Remember....Research is the key to your cure!"

Sunday, October 12, 2014

General Information from the Canadian Association for Porphyria

Information from the Canadian Association for Porphyria, 2009

A Guide To Porphyria

What are the causes of porphyria?


The porphyrin molecules are synthesized in the body from simple amino acids made up of carbon, nitrogen, hydrogen and oxygen. These amino acids interact under specific enzymatic control systems to form ALA then PBG and then on to the pyrolle rings. Each of the pyrolle rings has two side chains and the when the four pyrolle ring structures condense together to form a porphyrin, the combination of the eight side chains can form several variations called isomers. These isomers undergo further reactions where the side chains lose little segments containing carbon, hydrogen and oxygen and form an extensive variety of different molecules, all called porphyrins, but each has its own physico-chemical and biochemical properties. Most of these porphyrin molecules which are not involved in normal metabolic processes are produced in tiny amounts and are destroyed or eliminated as quickly as they are formed. These porphyrin degradation products are almost always water soluable and are excreted in the urine as uroporphyrins and in the stool as coproporphyrins. Only a very few of these isomers are clinical important and essential for life. The one with the highest concentration is the porphyrin molecule incorporated in hemoglobin, but the porphyrins are also present in other systems such as the cytochrome P-450 group of enzymes which are essential for many other metabolic processes. As the red cells age they in turn are degraded and the porphyrin ring structures are ruptured to form a long chain molecule called bilirubin which gives the bile its yellow green color. Most of the metabolic processes involving the porphyrins occur in the liver and in the bone marrow.

Each step in the synthesis, remodeling and destruction of the porphyrins is carried out by a sequence of chemical reactions under the control of enzymes. These enzymes are large protein molecules and are found in both the cytoplasm and the mitochondria of living cells. The rate of each specific chemical reaction is controlled by many factors, particularly the concentration and activity of the enzyme system. As a result they influence the concentrations of both the precursor and end products of the specific reaction. These enzymes are directly under the control of the DNA that is present in the chromosomes contained within the nucleus of the cells. The chromosomes have multiple condensations of coiled DNA which are called genes. The DNA in these genes makes RNA molecules, called messenger RNA which regulate the production of proteins including these enzyme systems.

In general, each individual gene influences several enzyme functions, and for the most part each enzyme system is under the control of multiple genes although the most of the specific enzymes involved in porphyrin synthesis seem to be encoded by single gene loci. . If the DNA composition of the gene is defective or abnormal, the metabolic functions that it controls probably will be defective as well. The 23 chromosomes themselves are paired, one set from the mother, and the other from the father with the result that apart from the x - y chromosome which is associated with the sex karyotype, all genes have duplicate representation in the chromosomes. If only one of the pair of genes is defective it can either be dominant to the other normal gene and alter the metabolic process, or be recessive to it in which case there will be no metabolic derangement. Rarely, both genes may have the same recessive characteristics, in which case the metabolic functions will be significantly altered. Although usually the gene is passed on intact via the ovum or sperm from parent to offspring, occasionally a change in the structure of the gene, called mutations can occur spontaneously and sometimes develop due to radiation, medications, etc. Many of the mutations of the individual genes involved in porphyria have been identified. Often the children of porphyric patients may be at risk of inheriting their parent's disease. At other times the disease may appear without any antecedent identifiable family involvement

Several problems can develop when the chemical reactions controlled by the specific enzymes are defective. If the enzyme process is slowed there may be a build up of potentially toxic precursors and if the chemical reaction is too fast the end products may accumulate in too high a concentration. Sometimes the abnormal enzyme systems change the direction of the reaction and produce abnormal metabolites. These precursors and end products can be retained within the cell cytoplasm where they may interfere with other metabolic processes or be sufficiently toxic to cause the death of the cells. Other water soluble compounds may be carried by the blood to other tissues such as the skin where they can absorb abnormal amounts of radiant energy and affect the body in a different way. Most compounds are simply excreted in the stool and urine in abnormal amounts without any clinical problem. In pregnancy, sometimes the abnormal compounds will not allow the developing fetus to survive. Other times the metabolic abnormality will not become apparent until well after puberty or even middle age. Frequently nothing will happen unless the enzyme abnormalities are changed or induced by other factors. Excesses of lead or iron overload syndromes, certain drugs such as barbiturates and sulfa drugs along with infections such as the virus that causes hepatitis C can either cause porphyria or bring out latent cases.
What are the different types of porphyria?


For the most part, the various syndromes that are classified under the collective name of porphyria are differentiated from each other on the basis of a combination of clinical symptoms and abnormal biochemical findings in blood, urine & stool. On the basis of our current understanding of molecular biology this classification is somewhat unsatisfactory and illogical. Theoretically it would be preferable to classify the porphyrias on the basis of the specific gene or enzyme defects giving rise to the abnormal prophyrin concentrations causing these abnormal clinical and biochemical findings. Unfortunately, much of the gene and enzyme studies have been carried out using ultra sophisticated techniques in specialized university research laboratories and are not yet available for common diagnostic clinical use. We still have to rely on the sometimes confusing terminology and laboratory testing.

One of the earliest classifications was based on whether the major activity of the defective enzyme system is associated with the liver (hepatic) or with the bone marrow (erythropoietic). Often however the same defective metabolic process takes place in both organs. The porphyrias can also be classified by identifying the specific tissues in which the abnormal porphyrin concentrations exert their major toxic effects such as in the skin where they are called cutaneous porphyrias or in the liver where they are called hepatic porphyrias. Other organs such as the nervous system are frequently affected. The disease may be considered to be acute with the sudden onset of serious life threatening symptoms, or it can be chronic with only minimally bothersome intermittent problems that develop gradually over months and persist for years. Very frequently, the disease is classified as latent because the patient is asymptomatic until some other outside stimulus such as drugs or sunlight initiates the onset of symptoms in a person who has the genetic predisposition for this disease. In these cases the patient may not even be aware that they are suffering from porphyria until something happens to change the activity of the enzyme system and precipitate the symptoms of the disease.
How will it affect me?


People with porphyria should be able to lead full active enjoyable lives with a minimum of limitations or difficulties. Many people, probably the majority of those who have the propensity for porphyria, go through their entire lives with the inherited gene defects and never know they have this disease. They are called asymptomatic carriers and may be considered to have latent disease. A few people have repeated or intermittent attacks of symptoms separated by long intervals or remissions between illnesses. Unfortunately a very few patients can become very sick and on rare occasions patients have died. Both the quality of life and the longevity are normal in most patients with porphyria, particularly if the precipitating and inducing causes can be avoided.
What are the symptoms of porphyria?


The symptoms of each type of porphyria depend on the concentration of the specific porphyrin or porphyrin precursors that are overproduced. Accumulations of ALA and possibly PBG, as in acute intermittent porphyria affect nerve endings and can cause a variety of neurovisceral symptoms and specific neurologic syndromes. The symptoms involve the nerves to the gastrointestinal tract where severe abdominal pain, often severe enough to be confused with acute appendicitis can develop and lead to exploratory surgery. There can be emotional and psychiatric problems such as anxiety, insomnia, agitation, confusion, paranoia, depression and hallucinations, although there is little evidence to suggest that porphyria itself is a cause of any of the chronic psychiatric syndromes.

Seizures fortunately are rare, as the anticonvulsant medications commonly used to treat seizures have been known to precipitate acute attacks in some patients. Many forms of peripheral neuropathy may develop involving either the motor system causing weakness, or the sensory system causing funny feelings or loss of sensation in various areas of the body. The autonomic or involuntary nervous system can be affected leading to problems such as high blood pressure, excessive sweating, rapid heart rate and changing bowel and bladder functions including constipation and urinary retention. The serum levels of sodium and magnesium can also be diminished through involvement of the neuroendocrine system. The severity and extent of these symptoms will vary from patient to patient and from day to day, depending in part on internal or endogenous factors such as menstrual hormone cycles along with external or exogenous changes including exposure to stress, drugs, sunlight, alcohol and even fasting. Sometimes these symptoms can be identified soon after birth, but usually they do not become apparent until the patient is a teenager or young adult.

Another very important group of symptoms is related to the fact that the completed porphyrin ring structure has the ability to store radiant energy, usually ultraviolet light with a wave length of about 400nm. For the most part this radiant energy is derived from exposure to bright sunlight. This energy build up within the cells can damage the subcellular structures. Certain of the porphyrins because of their structure are better able to concentrate this radiant energy more than others. This process is called photosensitivity or phototoxicity and it can cause many skin abnormalities. In an acute illness exposure to sunlight can cause tingling, stinging or burning skin discomfort during or soon after, followed by redness, rashes and blistering. Skin changes associated with chronic diseases can include scarring, increased or decreased amounts of hair growth, thickening of the skin of the exposed areas and increased skin fragility. It differs from sun burn in that it is recurrent and usually is not associated with prolonged or intense exposure to sun light.
How is porphyria diagnosed?


The diagnosis of porphyria is often difficult to make, in part due to the fact that the symptoms can mimic many other clinical states and the fact that the disease is sufficiently rare that most doctors have very limited personal experience with it. The recollection that some other member of the family, even a distant cousin, had this problem is often the key to the diagnosis. Since the multiple disease syndromes known as porphyria are all due to defective enzyme functions, there are abnormal accumulations of a variety of compounds involved in the metabolic pathway. Some of these are water soluble and so are freely excreted in the urine, others are found in feces after being metabolized by the liver and excreted into the bile. The classic laboratory finding that is described is the demonstration of red urine, either immediately on being passed or after standing in bright sun light. This is due either to the excretion of preformed porphyrin molecules or possibly by the nonenzymatic condensation of the high concentration of PBG into tetrapyrrole porphyrin molecules.

Ideally, the laboratory diagnosis of porphyria should be based on either the identification of the DNA structure of the defective gene or the measurement of the activity of the specific enzyme system that is affected. These procedures are not as yet available on a routine basis. As a result, the laboratory diagnosis still depends primarily on the tests which will identify abnormal concentrations of either the precursors of porphyrins or the porphyrins themselves or both. The compounds which are usually measured include PBG, ALA, uroporphyrin and coproporphyrin, and they are found in the urine, feces, plasma and red blood cells. When the diagnosis of porphyria is considered clinically, the initial screening test should be the determination of the concentration of PBG and ALA in a random sample of urine. Porphobilinogen production is elevated in AIP, VP, and HCP. There are several procedures used for these tests and most laboratories have upgraded their protocols to use the newest techniques in order to make the screening tests more specific and sensitive. The diagnostic tests for urinary PBG, ALA and porphyrin excretion are done on a 24 hour collections of urine and require specific preservatives. The urine should be collected in an opaque bottle and refrigerated to prevent the breakdown of the compounds. These tests are often difficult for the patient to complete as the urine must be collected and stored under very specific conditions and not all laboratories can do these tests. Although a sick patient will usually cooperate with the instructions for collection and storage of a 24 hour urine sample, many asymptomatic possible carriers of the gene who are being screened will not bother. In addition, the results are often not a true reflection of the changing metabolic state of the patient, they may be technically unreliable and are often difficult to interpret when they are borderline positive.

It is essential that before arranging for these tests, the doctor consult with the laboratory to ensure that the tests are available and also know the recommended procedures as to how and when to collect the blood, stool and urine samples. In addition, there is considerable overlap of the laboratory results between the various diseases, which complicates the difficulties of making a specific diagnosis. It can be very difficult to identify the patients with latent disease, particularly youngsters before the age of puberty. Some specialized university based referral laboratories will make other tests available using more sophisticated techniques. The activity of the enzyme porphobilinogen deaminase which is deficient in patients with AIP can be measured in their red blood cells and is available in some reference laboratories. In addition the technique of high performance liquid chromatography can be used to accurately measure the concentrations of porphyrins in the urine, stool and plasma samples.
Is porphyria treatable?


Simply put, the answer is yes. Prevention of the acute attacks in both known sufferers of the disease and suspected latent carriers is the most important approach. In a known porphyric patient it is essential to identify the factors that can precipitate the acute symptoms. The avoidance of porphyrogenic medications, bright sunlight or alcohol is often all that is necessary to avoid these attacks. In women with repeated premenstrual relapses, the inhibition of ovulation by the use of pituitary hormones or the LHRH analogues such as leuprolide may be effective in reducing their frequency. High carbohydrate diets are also helpful.

During the acute attacks, supportive therapy is required including narcotic analgesics, tranquilizers such as chlorpromazine, antinauseants, rehydration, sodium and magnesium replacement, high carbohydrate diets and sometimes intravenous therapy with high concentrations of glucose. Hematin and heme arginate, which are essentially the final products of the heme biosynthetic pathway can be given intravenously and act as specific agents to treat several types of porphyria by decreasing the activity of the enzyme ALA synthase, the first step in the heme biosynthetic cascade. The reduced activity of this enzyme slows down the entire metabolic pathway and stops the overproduction of ALA and PBG. However this drug must be used with caution as it can be associated with side effects.

During severe attacks the patient may on occasion require hospitalization. Seizures are often a difficult problem to control since many of the drugs used to control epilepsy such as Dilantin may precipitate or worsen attacks of porphyria. The anticonvulsant gabapentin has been shown to be effective and safe. Each type of porphyria has its own specific therapeutic program and it is important to try to identify the specific enzyme defect if possible. In cases of iron overload or lead toxicity the removal of the offending heavy metal excess may be all that is required. There appears to be some evidence that the treatment of hepatitis C with interferon and ribaviron may also be effective.

There are several drugs and medications used to treat other diseases that can precipitate an acute attack, but there are many more that are safe. It is preferable to take only the medicines that are absolutely essential. Before the patient with porphyria takes any drug they must ensure its safety. This is often difficult because of the limited experience of doctors, pharmacists and even university clinics in this field. If possible the family should check with the drug manufacturer or distributor about its porphyrogenic properties and history. The drug companies usually keep records of drug side effects. Most pharmaceutical houses have toll free phone numbers and are able to provide this information readily by fax or telephone. It is also important that the patients and the doctors share their knowledge and experience as widely as possible.
What about surgery or pregnancy?


Although there may be a risk of precipitating an acute attack of porphyria when a patient requires surgery, this problem can be either avoided or controlled by the application of preventative measures and the use of appropriate drugs and anaesthetic agents by knowledgeable physicians. However the entire medical team must be conversant with this disease. The risk of problems arising during pregnancy is also relatively minor and the symptoms can be easily managed. Every patient with porphyria should wear or carry with them some type of identification such as a Medic-Alert bracelet indicating the fact that they may be at risk for porphyria. Rather than concealing the fact, they should also ensure that their close family and friends know about their condition. The individual patient should make a point of becoming as knowledgeable as possible about their disease and their health.
What about my children?


Since porphyria is caused by a defective gene, it means that the children can be affected if one of the parents has porphyria. The inheritance of this gene can be classified as either dominant, in which case there is a 1 in 2 chance that the child will develop the disease, or as recessive in which case it will be very unlikely for the offspring to develop the problem. Although most types of porphyria are associated with a dominant inheritance pattern, the majority of the carriers of these abnormal genes will have latent disease and never develop symptoms and not be aware of this problem throughout their entire lives. Genetic counseling is available but most patients prefer to go about their lives in a normal fashion and deal with their family planning in their own personal fashion. The screening tests for porphyria may not become positive until after puberty but some clinics recommend periodic testing every few years starting at age 10 for children at risk of this disease. Many young patients do not bother with this testing since the test results are often unreliable and prefer to adopt a 'wait and see' attitude, while still following the appropriate preventative protocols.

Future prospects



Considerable progress has been made in the understanding of the genetic defects giving rise to the clinical and biochemical features of porphyria. The genes have been identified and decoded and mouse models of the disease have been made by genetic engineering. This should enable scientists to assess new treatments and allow pharmaceutical companies to test new drugs for their porphyrogenic properties. However these research advances have yet to be transferred into significant changes in the standard bedside medical practices and laboratory diagnostic techniques. It can be anticipated that this will change reasonably soon. Some very sick patients may benefit by the newer techniques of bone marrow and liver transplantation. However specific gene therapy is still a long ways away.

"Remember....Research is the key to your cure!"

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