Autumn 2006 PES Bulletin

The Porphyrias are Metabolic Diseases

Metabolism refers to the way in which our bodies turn the food we eat into life-giving substances through a multitude of complex chemical reactions.
A metabolic disease occurs when the body is unable to use (or metabolize) foods in the usual way.
Another way to "term" metabolic diseases is that of "inborn errors of metabolism".
There are a great number of metabolic diseases, or "inborn errors of metabolism", which have been identified.
The severity of these these metabolic disorders and the effect they have on the body varies.
Among these metabolic diseases are the porphyrias, a collection of at least eight separate diseases with a wide variations of mutations and subtypes.
Many, if untreated, affect the central nervous system, causing mental retardation and/or seizures.
Metabolic diseases may also cause damage to organs such as the liver, kidneys, and eyes.
While each metabolic disease is rare on its own, as a group they are a significant cause of illness, disability, and death.
Currently today with timely treatment the symptoms of the porphyrias can be controlled and mortality rates greatly reduced among porphyrics.

Garner Warwick PhD
Metabolic Disease Research Division

FECH and EPP

The FECH gene produces an enzyme called ferrochelatase. Ferrochelatase is the eighth and last enzyme in heme production.
Heme is the portion of hemoglobin that carries oxygen in the blood from the lungs to the rest of the body. Heme is an important part of the etiology of the porphyrias.
Each of the steps in heme production is controlled by a separate gene.
Ferrochelatase inserts an iron atom into the center of protoporphyrin IX.
Protoporphyrin IX the the main element of the seventh step in the heme production in mitochondria in heme formation.
The heme molecule is incorporated into hemoglobin and packaged into red blood cells, or it is used in the liver for the production of certain liver enzymes.
Mutations in the FECH gene can cause the inherited metabolic disease known as Erythropoietic protoporphyria.
Presently there at least 65 different mutations in the FECH gene which have been identified in patients with erythropoietic protoporphyria.
When a mutation is present in one copy of the gene, these mutations greatly reduce the activity of the enzyme made by the gene. To show symptoms of the disorder, however, a person must also have a particular version of the other copy of the gene. This variant, called a "low-expression allele," reduces enzyme activity even further.
Low levels of enzyme activity allele allow protoporphyrin (a byproduct of heme production) to build up in the body, which causes symptoms.
High levels of protoporphyrin in the skin cause sun sensitivity, and increased levels in the liver can result in liver damage.
The FECH gene in the human genome mapping is located at chromosone 18 q21.3.

Aubrey Varner PhD
Genetics

Hypoglycemia an Indicator of Porph

Hypoglycemia is often found to be a co-existing condition with those with the acute porphyrias.
Hypoglycemia occurs when your body's blood sugar, or glucose, is abnormally low.
Acute porphyria episodes often are preceded by low blood sugar readings.
Hypoglycemia results when your body's glucose is used up too rapidly, when glucose is released into the bloodstream more slowly than is needed by your body, or when excessive insulin is released into the bloodstream.
Hypoglycemia occurs when not enough food is eaten, or from a sudden increase in the amount of exercise without an increase in food intake.
Insulin is a hormone produced by the pancreas in response to increased glucose levels in the blood, which then reduces blood glucose.
Hypoglycemia is relatively common in diabetics.
Hypoglycemia can occur because of of the pancreas, liver disease such as the hepatic porphyrias.
Hypoglycemia can also occur as a response to the ingestion of alcohol.
When a person is hypoglycemic, likewise a hepatic porphyric, they make experience fatigue, uneasiness or malaise, irritability, trembling or sometimes seizures, tachycardia, sweats, confusion , blurred vision and even coma.
It is not uncommon for a person experiencing hypoglycemia to have muscle pain, memory loss, insomnia or even to faint.
For the porphyria patient monitoring their own blood glucose levels, readings will be around 55 or less.
As a "rule of thumb" porphyria patients should continually monitor their blood glucose levels and anytime there is a reading of 70 or below the patient needs to ingest carbohydrates.
A snack or drink containing sugar will raise the blood-glucose level, and you should see an immediate improvement in symptoms. This is especially true with drinking pure orange juice.
If the person's blood-sugar levels are so low that he/she becomes unconsciousness or unable to swallow, this is called insulin shock, and emergency medical treatment is needed.
Porphyria patients along with just hypoglycemic patients need to modify their dietary intake so that one can get glucose into their body more evenly throughout the day. This may prevent further hypoglycemic episodes.
Small, frequent meals with complex carbohydrates, fiber, and should be consumed.
It is important that meals be eaten at regular intervals including a carbohydrate snack before retiring to bed.
It is also important to balance extra exercise with extra food.
Severe hypoglycemia can often be avoided by recognizing the early warning signs of the condition and treating yourself rapidly and appropriately.
Untreated hypoglycemia can progress to unconsciousness and if the brain is exposed to reduced glucose for a long period of time, there may be permanent damage.
Porphyria patients who are known to experience hypoglycemia should keep a snack or drink containing sugar available at all times to take as soon as symptoms appear.
If symptoms do not improve in 15 minutes, additional food should be eaten.

Kim Cariveau MNS, NP
Endocrinology

Dioxin Exposure to Be Avoided by Porphyrics

There are innumeral ways that people can be exposed to dioxin.
For most people such exposure at mild levels is not harmful.
However for porphyrics even mild exposure can be most detrimental.
Dioxin can present as an unintended byproduct of natural events such as volcanoes and forest fires. Such expousre is minimal for most.
Most dioxin exposure comes from man-made processes such as manufacturing, incineration, paper and pulp bleaching, and exhaust emissions.
In the Pacific Northwestern United States there are higher incidents of chemical toxins involving dioxin.
It has been speculated for some time that the higher incidence can be traced to the use of chemical toxins that released in the lumber mills and the manufacturing of paper products.
Dioxin is ubiquitous in the environment: it is found throughout the industrialized world in air, water, soil as well as in food.
Exposure to dioxin can come through working in industries where dioxin is a byproduct, industrial accidents, through food and human breast milk and in drinking water.
It must be pointed out that skin contact or breathing represent very small sources of dioxin exposure.
Dioxin can enter the food supply through a number of different routes. In fish, the primary route of exposure is through water. Fish taken from streams downstream from paper mills can be largely suspect for chemical toxins.
Plants and animals are exposed to dioxin primarily through particulate in the air. Airborne particles of dioxin settle on forage or feed, which is then eaten by animals.This accounts for dioxin traces being found in milk.
Dioxin concentrates in the fatty tissues of beef and dairy cattle,poultry, pork or seafood. Theoretically, the longer the life span of an animal, the higher potential accumulation of dioxin in its adipose tissue.
Washing of fresh produce is a must. Dioxin particles that settle on fruits and vegetables as a result of airborne exposure are removed by washing; dioxin does not become systemic in the plant or food source.
Dioxin is stored in human adipose tissue.
Scientists recognize that the effects of dioxin vary widely among different animal species. Humans are less susceptible to the consequences of dioxin exposure than many of the animal species tested in laboratories.
Most research in humans has involved populations involved in occupational or accidental exposures of dioxin several thousand times higher than normal. Residents of Seveso, Italy are an example.

Phyllis Neis MNS NP
Metabolic Disorders