January 2006 PES Bulletin

Cardiac Medications for Acute Porphyrics

Acute porphyria patients can often have cardiac conditions in addition to their acute porphyria.
As with medical treatment for other conditions, porphyria patients need to closely review all cardiac medications that may be prescribed for use in treating their cardiac conditions.
The anti-arrhythmics are especially important to pay attention to.
Known to be safe for the treatment of irregular heartbeats are Procainamide and B-blockers.

However many other anti-arrhythmics have been found to pose real concerns for porphyrics. Among these contentious drugs are Lignocaine, Mexilitine, Bretylium and Disophyramide.
Some very commonly used anti-aahythmics are known to be completely unsafe cindluing Verapamil which has a variety of Brand Names, Nifedipine and Diltiazem.

Merrilyn Elder MNS NP
Patient Educator

Abdominal Distention a Common Symptom

Abdominal distention or a distnded stomach is a common clinical finding during acute episodes of porhyria.
Some porphyria patients refer to the condition as a swollen belly. Abdominal distention is marked by increased abdominal girth.
Abdominal distention is a common condition.
In normally healthy people abdominal distention usually results from over-eating, rather than from a serious illness.
In females PMS can be the cause of abdominal distention.
Abdominal distention is often caused by intestinal gas.
Abdominal distention may also occasionally result from the accumulation of fluid in the abdomen, which can be a sign of serious medical problems.
Abdominal distention is often caused by the porphyria itslf in those afflicted with the acute porphyrias.
Distention resulting from a heavy meal will go away when the food is digested.
Sometimes abdominal distention is caused by malabsorption of food, and malabsorption is often present in the acute porphyrias.
In the acute porphyrias the abdomen is often tender to the touch.
Often abdominal distention in porphyria patients will recede as the porphyric episode goes into remission.

Saul Korsmoe, PA
Gastroenterology

Psychosis Can Present in Attacks Mental changes can and do occur during acute episodes of porphyria.
Mental change like that of being psychotic in appearance can occur.
Psychosis in porphyria is often present during acute episodes but rarely remains into periods of porphyric remission.
Some porphyria patients will experience a loss of reality during acute episodes.
Psychosis is a loss of contact with reality. Having delusions is a typical form of psychosis that can present.
Such a psychosis find's the patient having false ideas about what is taking place. Sometimes the patients has trouble identifying who medical staff or caretakers are.
Another form of psychosis that often occurs is that of hallucinations.

True psychosis is a severe mental condition characterized by a loss of contact with reality.

Most psychosis in porphyria is transient.
Besides the porphyria itself, psychosis has several other potential causes including certain pharmaceuticals, alcohol, stroke, depression, brain tumors, and dementia.
When a porphyria patient is presenting with psychosis that most commonly have a loss of touch with reality.
Some patients are perceiving things that are not there through the presentation of hallucinations. They can hear, see or feel things which are not real.
Most often psychosis in porphyria patients will present with a disorganized thought and/or speech which often confuses emergency room personnel and delays treatment of the porphyria itself, and has at times caused a porphyria patient to be placed in a psychiatric ward rather than a medical ward.
Porphyria patients often display emotion which is exhibited in an abnormal manner. There may display extreme excitement which is often termed "mania".
Almost all porphyria patients experience confusion which is often tagged "brain fog".
Depression and sometimes suicidal thoughts can present during acute episodes of porphyria. A considerable number of porphyria patients have been victims of suicide.
Psychological evaluation and testing helps to pinpoint the exact diagnosis related to the psychosis.
Treatment varies depending on the cause of the psychosis, and fotr porphyria patients it means timely intervention with infusion of glucose and high carbohydrate intake as well as balancing electrolytes.
Care in a hospital is often needed to ensure safety of the patient.
Unforatunately psychosis prevents a person from functioning normally but fortunately in porphyria psychosis is usually slow lived.
During psychotic states, there is an inability to care for self, and the possibility of self-harm or harm to others if the underlying cause is left untreated.

Dr. Kenneth Carlson
Neuropsychiatric Medicine

Basic Genetics Helps Understanding

When a person is faced with an inherited metabolic disease is most helpful to have a basic understanding of genetics.
Human beings have cells with 46 chromosomes.
The 46 chromosones is composed of two sex chromosomes and 22 pairs of autosomal chromosones.
Autosomal chromosones are known as non0sex chromosones.
Males chromosones are "46,XY" and female chromosones are "46,XX".
These chromosomes are made up of extremely long DNA molecules in combination with chromosomal proteins.
Genes are defined by intervals along one of the DNA molecules.
The location of the gene is called the locus.
Most genes carry information which is necessary to synthesize a protein.
The pairs of autosomal chromosomes which originate one from one parent and one from the other parent, may carry basically the same information.
Each autosomal chromosone has the same genes, but there are slight variations in the DNA sequence of nucleotide bases in each gene.
These slight variations in the DNA sequence of each gene occur in less than 1% of the DNA sequence and produce different variants of a particular gene that are called alleles.
The information contained in the nucleotide sequence of a gene is transcribed to mRNA (messenger RNA) by enzymes in the cell's nucleus and then translated to a protein in the cytoplasm.
This protein may be a structural constituent of a given tissue. It may be an enzyme which catalyzes a chemical reaction, or it may be a hormone.
There are also many other potential functions for proteins.
If a gene is abnormal, it may code for an abnormal protein or for an abnormal amount of a normal protein.
In the inherited porphyrias there are abnormalities in various DNA.
Since the autosomal chromosomes are paired, there are 2 copies of each gene.
If one of these genes is defective, the other may code for sufficient protein. If it is coded for sufficient protein, no disease will be clinically apparent.
When this occurence happens this is called a recessive disease, and the gene is said to be inherited in a recessive pattern.
In the case of a recessive disease, if one abnormal gene is inherited, the child will not show clinical disease, but they will pass the abnormal gene to 50% (on average) of their offspring.
If one abnormal gene produces disease, this is called a dominant hereditary disorder.
In the case of a dominant disorder, if one abnormal gene is inherited from mom or dad, the child will likely show the disease.
A person with one abnormal gene is termed Heterozygous for that gene.
If a child receives an abnormal recessive disease gene from both parents, the child will show the disease and will be Homozygous for that gene.
If two parents are each heterozygous for a particular recessive disease gene, then each child has a 25% chance of being homozygous for that gene and therefore, of showing the disease.
If one parent is homozygous and the other heterozygous, then each child has a 50% chance of being homozygous.
These patterns are known as Inheritance.

Donovan Kenner PhD
Genetics

Toxic Neuropathy Often Possible

Toxic Neuropathy is often possible for porphyria patients.
Most porphyria patients develop sensitivities to many of today's environmental substances.
Porphyria patients can easily develop neuropathy from the very pharmaceuticals they are given in the course of treatment for their porphyria.
Drugs that cause neuropathy are known as "neurotoxic drugs" and should be avoided by porphyria patients.
Drug-related neuropathies are among the most common toxic neuropathies.

Enviromental chemicals can cause chemical neuropathy.
Such enviromental chemicals are found in chemical toxins, industrial chemicals, organic solvents, occupational exposure, environmental exposure, and today's wide array of pollutants.
Acrylamide; Arsenic; Carbon disulfide; Ethylene oxide; Lead;
Mercury; Methyl n-butyl ketone; Perchloroethylene; Styrene;
Thallium; Toluene; and Vinyl chloride are all known to cause Toxic Neuropathies.
Neuropathies from industrial agents (either from occupational or environmental sources), presenting after either limited or long-term exposure, are insidious.
Neuropathy for the most part is due to hereditary, metabolic, or inflammatory causes. However Toxic Neuropathy is on the increase and many porphyria patients have found themselves to be affected by exposure to environmental toxins.
A wide array of chemicals are known to cause neuropathy in laboratory animals.
Some laboratory findings have been associated with neuropathy in clinical epidemiologic studies, confirming their ability to injure the human peripheral nervous system (PNS).
Other chemicals have been reported to be associated with PNS dysfunction and neuropathy on the basis of retrospective and cross-sectional epidemiologic studies. Among porphyria researchers there is a wide division of thought concerning environmental toxins being a direct inducer of heme sythesis and triggering acute episodes of porphyria.
Human studies infrequently have associated exposure to environmental sources with peripheral neuropathy.
As compared to nonexposed controls, exposed individuals have statistically significant differences in nerve conduction velocity (NCV) and EMG findings.
Toxic Neuropathy presents in patients with subtle pain or weakness.
Subclinical abnormalities can be found on electrodiagnostic testing and may herald a progressive neuropathy if exposure continues at a similar dose.
Attributing neuropathy to such an exposure often is difficult.
In some patients, extensive search for an etiology may fail to uncover the exact cause of neuropathy.
In the porphyrias the cause of PN is usually left without an exact cause. Many porphyria patients have co-existing diabetes with it's own specific neuropathy.
Yet in other acute porphyria patients PN is often describe as related to SLE or moreover MS neuropathies.
In PCT especially, alcoholic neuropathy is often indicated.
Utilizing neurophysiologic testing, neuropsychological testing, and neuroimaging to support a clinical suspicion of PN is usully the best route to be undertaken.
Neuropathy may be described by it's presentation. Such description may be indicated as motor or sensory type smptoms. Both types are found in the acute porphyrias.
Other diagnostic measurements in neuropathy include electrodiagnostic features, and neuroanatomical location within the peripheral nerve. These diagnostic measurements can identify demyelinating or axonal, neuronopathy, ion channel neuropathy, neuromuscular transmission) or location (ie, cranial or peripheral).
Toxic neuropathy refers to those presentations that are caused by drug ingestion, drug or chemical abuse, or industrial chemical exposure which can often be found in today's enviroment.
Cellular involvement in neuropathy includes: (1) neuropathy affecting the cell body, especially those of the dorsal root ganglion, (2) myelinopathy or schwannopathy with primary segmental demyelination, and (3) distal axonopathy causing dying back axonal degeneration.
Distal axonopathy is the most common form,
Antibiotic treatment or cisplatin or pyridoxine toxicity may cause sensory neuropathy.
Segmental demyelination may result from the cardiac medications perhexiline or amiodarone, tetanus toxoid or diphtheria toxin administration, or exposure to lead or arsenic.
Through research studies conducted in the United States it has been found that 76% of patients who presented with undiagnosed neuropathy had neuropathies that were classifiable.
This research studies would then conclude that about 25% of all neuropathies have an unknown etiology.
Environmental and occupational exposure often play a role in some of these undiagnosed neuropathies.
Diagnosis of a pure porphyric neuropathy is difficult at best. Porphyria patients often developed multiple neuropathies.

Monte Mullendore NP
Neurology

Muscle Pain Common in PN

Muscle pain and weakness is commonly associated with porphyric PN.
Muscle pain in porphyric PN can be caused from muscle spasms, as well as from joints, and the bones themselves.
Muscle pain is a common complaint.
In normally healthy people muscle pain is most frequently related to overuse or muscle injury from unaccustomed exercise or work.
In the porphyric patient muscle pain is usually associated with the PN that is commonly associated with acute episodes of porphyria.
Muscle pain can accompany many conditions such as infectious disease, autoimmune disease, parasitosis and other problems, as well as the acute poprhyrias.
Tension and stress can add to muscle pain.
In addition some pharmacueitcals can be the cause of muscle pain. Such pharmaceuticals include amphotericin B, carbinoxolone, chloroquine, clofibrate,corticosteroids, and hydroxychloroquine.
Muscle pain is best relieved through plenty of rest and exercise. Many porphyria patients follow prescribed physical therapy workouts to relieve such pain.
Muscle pain will often respond well to cold and/or warm compresses.
Muscle pain also can be relieved through body massage.
Heat, warm baths, massage, and gentle stretching exercises after a rest period should be used as frequently as possible.
Regular exercise is strongly recommended.
In severe cases the use of TENS units can be beneficial.
Pain medications may help relieve pain and swelling.
Muscular pain associated porphyria is best controlled by treating the primary illness and avoiding acute episodes.

Karen Butterfield PT
Physical Therapy & Rehabiliation