June 2006 PES Bulletin

Neuropsychological Aspects of Porphyria

Today in the agressive and preventative treatment strategies for for patients with the acute porphyrias, the neurological aspects of the disease can be well controlled.
Improved glucose protocol for intervention therapy during acute attacks have greatly reduced the excerbation of numerous neurological symptoms considerably.
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 three main types of porphyria that give rise to neuropsychiatric disorders include the acute intermittent porphyria [AIP], variegate porphyria [VP] and the heriditary coproporphyria [HEP].
In a medical publication entitled "The Little Imitator" written by H.L. Crimlisk, of the Department of Neuropsychiatry at the Institute of Neurology in London, England, the author states that nerological or psychiatric symptoms occur in most acute attacks.
While true of symptomology of earlier years, today these neuropsychological symptomologies can be treated early on, by porphyric patients learning to be "in tune" with their mind and bodily functions.
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.
In times past many porphyria patients experience bizarre psychological behavior and often would be hospitalized in neuropsychological wards due to the behavior rather than the treatment of the porphyria.
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, and then immediate and agressive treatment.
Today the neurological aspects can be avoided and/or controlled for the msot part. Earlier and timely intervention is a necessity!

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

Always Review Anesthesia Drugs

Safety of drugs commonly used in clinical anesthesia for patients with acute porphyrias need to be reviewed when an acute porphyria patient is scheuled for surgery or to undergo medical procedures requiring anesthesia or conscious sedation.
Intravenous induction agents that are known to be safe for use in acute hepatic porphyrics include Midazolam commonly known as Versed.
Another long used induction agent is Propofol.
The use of Ketamine in acute hepatic porphyria patients is considered contentious.
Unsafe are induction agents include all Barbiturates and Etomidate.

Merrilyn Elder MNS NP
Patient Educator

Heme Biosynthesis is the Backbone of the Porphyrias

Heme is synthesized in largest amounts by the bone marrow. In the bone marrow the heme is incorporated into hemoglobin. The hemoglobin which is an oxygen transport protein takes it from there.
The heme is then off to the liver. At the liver the heme is metabolized by the liver, where most of the heme is incorporated into cytochromes.
The cytochromes are electron transport proteins.
The most abundant cytochromes in liver are the cytochrome P-450 enzymes that metabolize drugs and many other foreign and endogenous chemicals.
It is for this reason that all porphyrics must be very careful in avoiding all drugs that metabolize in the liver. They are often referred to as P-450 drugs or toxins.
Heme biosynthesis is controlled differently in liver and bone marrow.
Hepatic heme biosynthesis is rate-limited and primarily regulated by the first enzyme, ALA synthase. This enzyme's activity in liver cells is normally very low but increases dramatically by induction of enzyme synthesis when the liver produces more heme.
Certain drugs and hormones induce hepatocytes to make more ALA synthase, heme, and cytochrome P-450.
In the bone marrow, heme is made in erythroblasts and reticulocytes that still contain mitochondria, whereas circulating erythrocytes lack mitochondria and cannot form heme.
Bone marrow cells express erythroid-specific forms of some pathway enzymes.
Porphyrias and related disorders are associated with deficiencies of the other seven enzymes, and mutations in genes for these enzymes have been characterized in detail in previous PES bulletins.
Although each type of hereditary porphyria is associated with deficiency of a particular enzyme, unless people with that enzyme deficiency come from the same family, they are likely to have different mutations in the gene for that enzyme. Because of this factors these diseases are heterogeneous at the molecular level.
Some porphyrias, especially those that increase the early precursors ALA and PBG, damage nerves, leading to a variety of symptoms such as abdominal pain and muscle weakness, which can even progress to paralysis.
Mechanisms for the neurologic disturbances have been speculated, such as effects of excessive heme pathway intermediates, or deficient heme synthesis, in the nervous system. ALA and other products of the heme biosynthetic pathway have not been proven to be neurotoxic, and heme deficiency in nervous tissue in these disorders is also unproven. Therefore, the exact cause remains unclear.

Robyn Jefferies PhD
Molecular Sciences Division

Hypoglycemia an Indicator of Porphyria

Hypoglycemia is often found to be a co-existing condition for 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 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, 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