April 2006 PES Bulletin

Muscle Relaxants Vary Widely in Safety

The use of muscle relaxants in acute porphyria patients varies widely.
Known to be safe for use are those of Curate, Sexamethomium, and Vocuronium.
Two muscle relaxants have been indicated as triggers of porphyria attacks and are considered contentious for use. These include Atracurium and Pancuronium.
Long known as a definite trigger is that of Alcuronium which appears on many Unsafe drug listings.

Merrilyn Elder MNS NP
Patient Educator

Better Treatment Reduces Mortablity Rate

Care to avoid relapses of remission in patients diagnosed with acute porphyrias and the improved glucose protocol for intervention therapy during acute attacks have reduced the mortality of porphyria patients considerably over the last decade, however there are still problems with the neurological aspects of porphyria.
When porphyria patients are in remision there are usually little or no neuropsychological problems except in patients with a long history of acute attacks and of course in those who have a chronic prognosis.
The early use of propranolol, adequate rest, control of seizures, nausea and vomiting and lab tests checking electrolyte balance, all can correct if not inhibit the neuropsychological problems of earlier etiology of acute attacks.
The management of patients with porphyria and the psychiatric symptoms do cause considerable problems unless the porphyria is actively addressed first and foremost. This calls for adequate testing and diagnosis.

Betsy Perkins, MNS
Director of Case Management
Inherited & Metabolic Disease Division

Edema often Present in Porphyria

Edema is no stranger in the porphyrias.
There is often ankle sweeling, foot swelling, and even swelling of the legs.
Sometimes such smptoms are referred to as perpheral edema. Peripheral edema is an abnormal buildup of fluids in ankle and leg tissues.
Most edema is painless. Painless swelling of the feet and ankles is a common problem.
Edema may affect both legs and may include the calves or even the thighs.
Edema is very noticeable in the lower legs. The prominent in the lower legs is due to the effect of gravity.
When the swollen area is squeezed, the fluid will move out of the affected area and may leave a deep impression for a few moments. This is medical known as "pitting edema".
In porphyria edema is often related to co-existing conditions involving the kidneys, heart or liver.
Often edema is due to a build of of sodium in the body.
When edema is present it is most beneficial for the porphyria patient to avoid foods containing salt.
It is also beneficial for the porphyria patient to elevate their legs above the heart while lying down.
When edema is present it is good to avoid sitting or standing without moving for prolonged periods of time.
When lying down, one should avoid putting anything directly under the knees.
It is good to remember that a person should not wear constricting clothing or garters on the upper legs.
Exercising the legs causes the fluid to work back into the veins and lymphatic channels so that the swelling goes down.
Elastic bandages or support stockings can provide pressure to help reduce ankle swelling.
Sometimes dieuretics may be prescribed. Dieuretics are effective in reducing the swelling. Remember that in porphyria patients some dieuretics have side effects.

Dalsha Higdem NP
Internal Medicine

Suicide and Porphyric Pain

Throughout much of the known history of porphyria, there have been those porphyrics who have ended their lives. Most notable of these porphyrics was of course the famed Vincent Van Gogh.
His problem of course was that when he went into a poprhyic attack, he would drink a thimble of absythe to dull the severity of the pain. And it may for a short time, but at the same time was the "trigger" for another acute attack of porphyria. It happened so often that Van Gogh was chronic and no longer just a smoldering chronic porphyric but in severe chronic pain.
Finally, unable to handle his condition he commited suicide.
Suicide is NOT a treatment for anything. This same thought was stated recently in an article in a California mainline newspaper publication where the "right to die" is being discussed.
Debate started in the California legislature regarding physician-assisted suicide with the introduction of Assembly Bill 1592.
Rather than debate such issues to end life, it should rather be the issue of requiring physicians to include courses that familiarize them with the diesease porphyria and addressing pain and symptom management of the various types of porphyria.
Another issue that needs to be stressed is to be sure that pain medications are readily available to porphyria patients in pain.
Legislation also has to be made clear that allows for physician caring for porphyric patients to prescribe appropriate dosages of medications without fear of the wrath of the law enforcement officials intent on the waging of war on drugs.
Laws have been enacted to allow access to pain medications and reduced the inefficiancy of the triplicate prescription process for administering drugs to terminally ill patients. Those suffering from a terminal illness are no longer subject to long delays in approval of non-formulary medications.
However, porphyrics are not terminal, but many days it seems as if we wish the porphyria were terminal. It is not.
Moreover, suicide is not an answer.
We must be sure that legislation is made that will enable our physicians to prescribe the medications that we need in order to live a better quality of daily life.
All concerned parties should work together for the behalf of porphyrics and continue dow the humanitarian path of treating pain in suffering individuals both porphyrics and others in severe pain.

Jeffrey Lange NP
Pain Management Specialist

PPOX Genes : Protoporphyrinogen Oxidase & VP

Protoporphyrinogen oxidase is an enzyme which is produced by a gene known as PPOX.
The Protoporphyrinogen oxidase enzyme is very important because it is responsible for the seventh step in heme production.
Heme is the portion of hemoglobin that carries oxygen in the blood from the lungs to the rest of the body.
The synthesis of heme is the vital to the understanding of the porphyrias.
Each of the steps in heme production is controlled by a separate gene.
Protoporphyrinogen oxidase removes hydrogen atoms from protoporphyrinogen IX.
Protoporphyrinogen IX is a vital element of the sixth step in the production of heme.
Only one additional enzyme must modify protoporphyrin IX before it becomes heme.
Porphyria patients who learn the etiology of their disease become familiar with the terms delta-aminolevulinate acid, uroporphyrinogen decarboxylase (UROD) , ferrochelatase, and coproporphyrinogen oxidase.
The PPOX is most known to those patients with VP (variegate porphyria).
More than 100 mutations that can cause variegate porphyria have been identified in the PPOX gene.
One specific mutation of PPOX is that of R59W.
The R59W mutation has been identified in about 95 percent of South African families who are diagnosed with variegate porphyria.
Mutations in the PPOX gene reduce the activity of the enzyme made by the gene, allowing byproducts of heme production to build up in the body. This buildup, in combination with nongenetic factors (such as certain drugs, alcohol, and dieting), causes the symptoms seen in this type of porphyria.
The PPOX gene is mapped at chromosome 1q positon 22.

Byran Jenkins PhD
Genetics