Spring 2006 PES Bulletin

Neurotoxins and Neuropathy in Porphyria

Neurotoxins affect the neuromuscular junction and can cause flaccid paralysis.
Not all neurotoxins affect the same sketetal locations nor the same mode of action or clinical effects.
Some neurotoxins affect the neuromuscular junction.
The neuromuscular junction involves all voluntary and respiratory muscles.
Some neurotoxins affect the terminal axon through incompletely understood mechanisms, resulting in disruption of synaptic vesicles, damage to the terminal axon and cessation of release of Ach, thus completely blocking neuromuscular transmission.
This causes flaccid paralysis of affected muscles. However, the process is not instantaneous.
Neurotoxins need to be absorbed, reach circulation and bein damage.
This process can take from 30 minutes to several hours.
The clinical features of early paralysis are usually first seen in the cranial nerves.
Once severe flaccid paralysis is established, with respiratory involvement, it is very hard to reverse paralysis.
It is therefore crucial to recognize the early signs of paralysis and seek medical attention.
Other forms of neurotoxins are more common, and also less potent.
These form are often more rapid in action and can be lethal in potential.
Not all neurotoxins cause flaccid paralysis.
Some neurotoxins affect the autonomic nervous system.
There are also a wide array of neurotoxins which cause hyperstimulation of parts of the nervous system.
Neurotoxins of any type should be avoided by persons with acute porphyrias who are at a higher risks for side effects and great complications, especially respiratory paralysis.

Kevin Streifel PhD
Pharmacology & Toxicology

Molecular Genetics of the Porphyrias

The molecular genetics of the porphyrias is very heterogenous.
Nearly every family has its own porphyria mutation. The mutations identified account for the corresponding enzymatic deficiencies, which may remain clinically silent throughout life.
The clinical identification of the overt disorder with extrahepatic manifestations depends on the demonstration of biochemical abnormalities due to these primary defects and compensatory hepatic overexpression of hepatic delta-aminolaevulinic acid synthase in the acute porphyrias.
Heme precursors are synthesized in excess.
The increased metabolites upstream of the enzymatic defect are excreted into urine and stool.
Porphyria diagnosis is based on their evaluation.
Some molecular analyses may lead to incorrect diagnosis as well as initial enzymatic analyses.
Often there is a high amount of delta-aminolaevulinic acid and porphobilinogen.
It is possible that some homozygous or compound heterozygous variants of acute hepatic porphyrias may manifest in childhood.

Erin MacBrady PhD
Metabolic Disease Research

Diagnosis of Dual Porphyrias Possible

Disorders resulting from deficiencies of more than one enzyme of the heme biosynthetic pathway can occur resulting in the diagnosis of more than one form of porphyria.
Although mutations in heme biosynthetic pathway enzymes are uncommon, occasionally a single person may inherit a deficiency in more than one of these enzymes.
For example, patients with deficiencies of both uroporphyrinogen decarboxylase and protoporphyrinogen oxidase have been described.
People who have inherited deficiencies of both PBG deaminase and uroporphyrinogen decarboxylase may have symptoms of acute porphyria, cutaneous porphyria, or both.
Dual porphyrias due to deficiencies of both coproporphyrinogen oxidase and uroporphyrinogen III cosynthase, and PBG deaminase and coproporphyrinogen deaminase, have also been described.

Robert Johnson MD
Internal Medicine

Cutaneous Symptoms in Erythropoietic Porphyrias

Erythropoietic porphyrias are characterized by cutaneous symptoms.
Erythropoietic porphyrias appear in early childhood unlike most of the hepatic porphyrias which have a late onset.
Porphyrias are divided into erythropoietic and hepatic manifestations.
Characteritic of Erythropoietic protoporphyria are the accompanying complications of cholestatic liver cirrhosis.
Additionally in Erythropoietic protoporphyria there can be progressive hepatic failure in 10%, of patients.

Erin MacBrady PhD
Metabolic Disease Research

Porphyria and Treating Pain

Pain medications are known as analgesics.
Pain medications vary considerably.
Each pain medication has its own advantages and risks.
Specific types and causes of pain may respond better to one kind of pain medication than to another kind. In treatment of pain it is good to remember that no one medication will treat all forms of pain, in other there is no "one size fits all".
In addition, each person is slightly different in the way they respond to a pain medication.
Over-the-counter medications are good for many types of pain.
Acetaminophen is good for relieving pain and fever. The most common form, Tylenol, It is less irritating to the stomach than other over-the-counter pain medications and is safer for children.
Howebver for porphyria patients it is wise to remember that Tylenol can, however, be toxic to the liver in high doses.
Aspirin, naproxen and other non-steroidal anti-inflammatory medications (NSAIDs) are good for reducing inflammation caused by injury or arthritis.
Prescription medications may be needed for other types of pain.
Non-narcotic and narcotic medications (narcotic analgesics - oral) have their specific uses and risks.
It is most important that porphyria patients and attending/prescribing physician both review Unsafe Medication listing looking both at the brand names and generic name listings.
For many porphyria patients other methods may help reduce pain instead of pain medications.
Such alternative methods may include the use of TENS units, electric mattress covers, heat, cold, massage, resting or gentle use of the affected part, biofeedback, and various relaxation techniques.

Marilyn Pholx MSN RN
Patient Educator