March 2006 PES Bulletin

Analgesics and Treatment in Acute Porphyrias

Analgesics are commonly used in the treatment of episodes of acute porphyria.
Most analgesics are considered safe. Those with a known safety record include Demerol, Morphone, Fentanyl, Buprenorphone, Naloxone and Patacetamol.
Even though most anlgesics can be used there are some which are considered contentious due to reported incidences and side effects.
Considered contentious for analgesics use in porphyria patients are Alfentanil and Sufetanl.
There are only two analgesics which are undeniably unsafe for use in porphyrics, those being Pentazocine and Tilidine.
Porphyria patients along with their attending physicians should always review medications against multiple listings of Drug listings for treatment of the acute porphyrias.

Merrilyn Elder MNS NP
Patient Educator

The Role of Genetics and Illness

Genetics is what is our make-up as human beings.
Genetics has a whole voculary of it's own including such terms as Homozygous; Inheritance; Genes, Chromosones, Heterozygous; Inheritance patterns; Heredity and disease; Heritable; and of course Genetic markers.
For many years it has been known that a person's appearance are determined by their genes. Such determinations include a person's skin color, eye color, height, and many other factors.
A person's mental abilities and natural talents are affected by heredity.
Inherited diseases are also determined by one's genes.
All but one of the many porphyrias are inherited and are determined by one's genetics. Most porphyrias are known as inherited metabolic diseases.
An inherited, abnormal trait or "anomaly" may present no real consequence to a person's health or well being especially if an inherited disease remains latent.
However, too often carriers of inherited genetic defects can be triggered and become acute.
It must be remembered that too often the terms anomaly, abnormality, disorder, defect, disease, and syndrome are not used consistently, and do not have precise definitions.
The main terms in porphyria are "acute", "latent," "chronic" and "carrier". Almost all diseases have a genetic component, but the importance of that component varies.
The porphyrias have varying components.
Disorders where genetics play an important role, so-called genetic diseases, can be classified as single gene defects, chromosomal disorders, or multifactorial.
Single-gene defects are also called Mendelian disorders.
The porphyrias are a Mendelian disorder.
A single gene disorder is one that is determined by a single genetic locus and the specific allele(s) on one or both members of a chromosome pair.
Single gene defects are often rare, with a frequency of less than 1 in 200 births.
But since there are about 6,000 known single gene disorders, their combined impact is significant.
The incidence of serious single gene disorders is estimated to be about 1 in 200 births.
Single-gene disorders are characterized by the pattern of transmission in families -- this is called a pedigree.
A kindred includes the relatives outside of the immediate nuclear family.
The affected individual that initially comes to light (or is of immediate interest) is called the proband.
The brothers and sisters of the proband are called siblings.
There are only 5 basic patterns of single gene inheritance:

Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive
Maternal (mitochondrial) inheritance
Most of the porphyrias are of the single gene inheritane and are autosomal dominant. Only some rare forms of porphyrias carry the autosomal recessive inheritance.
The observed effect of an abnormal gene (the appearance of a disorder) is called the abnormal phenotype.
A phenotype expressed in the same way (in both homozygotes and heterozygotes) is dominant.
A phenotype expressed only in homozygotes (or, for X-linked traits expressed in males but not females) is recessive.
Heterozygotes for a recessive gene are called carriers. They usually don't express the phenotype clinically, but it can frequently be identified by sensitive laboratory methods.
In autosomal dominant inheritance, the abnormality or abnormalities usually appear in every generation.
Every affected child has an affected parent and each child of an affected parent has a 50% chance of inheriting the disease.
Normal members of the family do not transmit the disease.
Males and females are equally likely to have the disease and to transmit the disease.
Male-to-male transmission can occur (unlike with X-linked inheritance), and males can have unaffected daughters (unlike with X-linked dominant inheritance).
In autosomal recessive inheritance, the parents of an affected individual may not express the disease.
On average, the chance of an affected child's brothers or sisters having the disease are 1 in 4.
Males and females are equally likely to be affected. For a child to have symptoms of an autosomal recessive disorder, the child must receive the defective gene from BOTH parents.
Because most recessive disorders are rare, a child is at increased risk of a recessive disease if the parents are related (related individuals have a higher probability of having inherited the same rare gene from a common ancestor).
In X-linked recessive inheritance, the incidence of the disease is much higher in males than females.
Since the abnormal gene is carried on the X chromosome, males do not transmit it to their sons -- they do transmit it to all their daughters.
The presence of one normal X chromosome masks the effects of the X chromosome with the abnormal gene.
So, almost all of the daughters of an affected man appear normal, but they are all carriers of the abnormal gene.
The sons of these daughters then have a 50% chance of receiving the defective gene.
In X-linked dominant inheritance, the presence of the defective gene makes itself manifest in females even if there is also a normal X chromosome present.
Since males pass the Y chromosome to their sons, affected males will not have affected sons, but all of their daughters will be affected.
Sons or daughters of affected females will have a 50% chance of getting the disease.
Differences in genetic makeup cause the differences found in the various porphyrias. Such differences include dal traits, and porphyria type overlaps.

Donald Hartwig PhD, MS
Genetics

Dysuria Often an Attack Symptom Dysuria is the medical terminology used to describe painful urination.
Dysuria includes the process of difficulty in urinating.
Dysuria involves pain, discomfort, or burning sensation during urination. Pain on urination is a fairly common problem.
Dysuria is most often caused by an infection somewhere in the urinary tract.
Some of the other causes of Dysuria common in the porphyrias includes that of bladder distention. and urinary retention.
If a urinary tract infection is confirmed or highly suspected, treatment will include the prescription of an antibiotic.
If appropriate, pain medications will be administered.
It is especially important to be sure that your attending physician is aware of porphyria and that prescribed medications are not contraindicated for porphyria.

Jean Jostad NP
Urology

Diagnosis of PN in Porphyria Porphyria patients with neuropathy typically present with symptoms of pain, tingling, or numbness in their feet, consistent with dysfunction affecting the longest and largest fibers of the peripheral neurological system (PNS).
In some cases, porphyria patients may have weakness or difficulty with gait.
Such weakness is usually more distal than promimal.
The examining neurologist needs to exercise a high index of suspicion to uncover toxic etiologies, and even more so to pinpoint a pure porphyric neuropathy.
A patient’s beginning a new medication in the last few weeks or months should raise a red flag.
Most important, the search for an underlying chronic disease is the most common workup ordered; however, new medications are commonly a culprit.
When looking for PN caused by porphyria, the examining neurologist must also consider the possibility of other conditions that commonly co-exist with the acute porphyrias such as diabetes II, SLE (lupus), and MS, as well as the use of alcohol especially in PCT forms of porphyria.
Toxic neuropathy due to chemical abuse may be more difficult to uncover than occupational or environmental exposures, since direct questioning of the patient may lead to incorrect information.
In some cases of PN presentation, a dramatic systemic reaction leads to an emergency room visit because of an acute alteration of consciousness, heralding the diagnosis of drug abuse.
Neuropathy, in these cases, may present over a few days to weeks since the dose is often higher than in prescribed-medication settings.
After a high-level acute exposure, an etiology for toxic neuropathy may be easier to consider, since low exposure usually leaves the patients and the clinician alike with vague etiology oif symptoms.
Often a differential diagnosis ruling out more common causes of neuropathy is mandatory to establish the cause of neuropathy.
Befoe the appearance of PN symptoms, subclinical findings on EMG or NCV studies may be apparent and consistent with axonal or demyelinating abnormalities.
Some toxic exposures can be revealed by electrodiagnostic techniques.
Most helpful is pain or numbness in the distribution of the trigeminal nerve suggests a disorder of that nerve.
PN presents clinically as a “triad of sensory changes in a glove and stocking distribution, distal weakness, and hyporeflexia.
Sensory changes include sensory loss in a stocking-glove distribution.
Often, progression in PN is distal to proximal. This is consistent with the commencement of axonal degeneration.
Early loss of symmetrical ankle jerk is noted.
In severe cases, motor dysfunction such as abnormal gait and foot drop also may occur.
All of these conditions can and do occur in porphyric PN.
Recovery proceeds at a rate of 2 mm/day and may take months or several years, or may never be complete.
Function is restored in reverse order to the sequence of loss.
"Coasting" may be noted, that is, intensification may occur for weeks before improvement. This often reflects continued axonal degeneration and reconstitution.
Signs of CNS disease also may be present at examination.
This occurs in some patients recovering from certain toxic neuropathies.
Dorsal column or corticospinal tract degeneration may be present.
These clinical signs of degeneration are not prominent early in the illness; however, the patient may manifest hyperreflexia.
Involvement of the autonomic nerves may lead to a different clinical presentation.
There may be vasomotor abnormalities. These may occur with or without evidence of a peripheral neuropathy.
Tachycardia, rapid alterations in blood pressure, flushing and sweating, and abnormalities in gastrointestinal motility may be present, which is commonly associated with acute attacks of porphyria and thus may veil the onset of PN.
Tendon reflexes may be absent.
Nerve cell velocity (NCV) results usually are normal.
Sensory nerve potentials may be abnormal or absent.
Recovery in PN is variable, reflecting the death of nerve cell bodies and consequent permanent loss of axons.
Collateral sprouting from surviving axons may account for the extent of recovery in these conditions.
Electromyography (EMG's) and nerve conduction (NCV's)studies are the foremost used diagnostic studies used in determining PN once laboratory studies have ruled out toxic causes of PN.
Such diagnostic studies can reveal normal to mildly slow motor NCVs in PN.
Sensory amplitudes are frequently diminished in porphyria.
Most often in porphyria there is EMG evidence of denervation characterized by symmetrical fibrillation potentials in distal muscles
EMG's are helpful to establish the duration of the disorder and identify ongoing reinnervation that is occuring.

Gerald Griffith PA
Neurology

Pain Medication in Porphyria

Pain medications vary in types and functions.
Analgesics are known as pain medications.
Pain medications vary considerably, they are not all the same.
Each pain medication has its advantages and risks.
Specific types of pain may respond better to one kind of medication than to another kind.
Each individual porphyria patient may have a slightly different response to a specific pain medication.
Over-the-counter medications are good for many types of pain.
Acetaminophen which is better known as Tylenol has been found to be beneficial for relieving pain and fever. Tylenol is less irritating to the stomach than other OTC medications.
Tylenol however, can be toxic to the liver if the recommended dose is exceeded. Many physicians do not recommend the use of Tylenol in hepatic porphyria patients because of possible further liver damage.
NSAIDs are another classification of pain medications
NSAIDs is the short term for non-steroidal anti-inflammatory drugs.
Aspirin, Alleve, Naproxen, Advil, Motrin, and ibuprofen are examples of non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs reduce inflammation thus relieving pain.
Prescription medications may be needed for other types of pain.
Non-narcotic and narcotic pain medications have their specific uses and risks.
Besides pain medications pain can often be relieved through the use of TENS units, massage, biofeedback, relaxation techniques, ice or heat packs.
Some porphyria patients have found that a consultation with a pain clinic or other specialist may be helpful for control of long-term pain.

Dallas Engstrom PA
Pain Management Center