Porphoria - Non-genetic, Secondary Porphyria and Genetic Primary Porphyria
No longer sure where this comes from so it cannot be referenced however, it is posted elsewhere here. I find the list fo nervous system symptoms useful when I look at porphoria is is a factor at any point in the treatment experence. In treatment most are concerned with the secondary form of the condition, but to know something about the primary form can lend some perspective.
About Porphyria - Primary porphyria is a genetic disease in which there is a deficiency of one of eight different enzymes, each of which is required to effect one of the eight sequential steps required to synthesis the iron-containing prosthetic group, hemei.
The output at each step of synthesis is the precursor for the next step of heme synthesis. A deficiency of one of the enzymes can cause accumulation of the precursor from the previous step and prevent the subsequent steps from producing heme.
Normally, finished heme feeds back to the first of the eight steps, and halts heme production when sufficient heme has been synthesized. In primary porphyria, heme production is compromised, and heme feedback isn’t sufficient to halt the continued attempt to synthesis heme, and one or more of the precursors continue to accumulate, in an out-of-control, open loop process.
These precursors, called porphyrins, are highly neurotoxic, though normally they exist only transiently in the intracellulari heme manufacturing pipeline, and thus are not problematic.
In primary genetic porphyria, not all porphyrins are converted to heme and thus accumulate to excess. When accumulated to sufficient levels porphyrins are released from the intracellulari space into general circulation, and thus result in the various systemic manifestations of the various forms of porphyria. Only about 10% of those possessing the genetic defect have the active disease triggered.
The most common of the four acute neuropathic types of porphyrias isn’t typically triggered sooner than the end of the fourth decade of life.
Non-genetic, secondary porphyriai is similar in function and nature to genetic porphyria, with the main difference being that secondary porphyria is not caused by a genetic shortage of heme-pathway enzymes, but instead the heme-pathway dysfunction is caused by some non-genetic environmental factor. Both alcohol and chemical exposures are known to result in both transient and chronic secondary hepatic porphyria.
However, the recognition of secondary porphyria as a consequence of infection is very limited, and secondary porphyria as a consequence of Cpni infection has been recognized among only a small number of researchers. Never-the-less, laboratory research and clinical experience have established that Cpn infection can indeed cause secondary porphyria.
While all cells manufacture some amount of heme, the greatest amount (65%) of heme is manufactured during the production of red blood cells. Most of the rest of the body's heme is manufactured by the liver. Red blood cell production is a relatively steady-state operation, with total RBC heme turning over approximately every 120 days. The liver, on the other hand, is involved in large numbers of processes that are anything but steady state, but instead, are highly dynamic processes responding to a variety of external stimuli.
An examination of classical porphyria triggers such as alcohol consumption, tobacco consumption, intense exercise, illicit and licit drug consumption, dietary factors, and blood-sugar regulation reveals that these are all environmental factors that heavily impinge upon liver function.
In most cases of porphyria, both primary and secondary, the body is capable of successfully producing normo-intensive amounts of heme, and production of excess porphyrins does not occur under normal circumstances, or occurs at some relatively steady-state chronic level. However, events that cause the need for amounts of heme greater than can be produced by the dysfunctional biosynthetic pathway can trigger the open-loop production of porphyrins. Such triggers include many circumstances causing the need for increased hepatic function, such as metabolism of exogenous or endogenous substances. Since most of these events trigger production of heme in the liver, porphyria is essentially a disease of the liver.
Once an acute porphyria attack is triggered, removal of the original trigger won’t necessarily halt the open-loop dysfunctional heme manufacture. Treatment involves infusion of glucose, or infusion of Panhematin (derived from human blood), which closes the open feedback loop of heme biosynthesis. Classic triggers include alcohol consumption, smoking, intense exercise, hundreds of known porphyriogenic drugs, organic solvents, pesticides, and other chemicals, low-carb and calorie-restricted diets, infectionsi, hormonal cycles, and physical and mental stress.
Porphyrins, when they accumulate in the skin, cause forms of porphyria called erythropoietic porphyria, which primarily affect the skin, causing photosensitivity (photodermatitis), blisters, necrosisi of the skin and gums, itching, and swelling, and increased hair growth on areas such as the forehead.
Porphyrins are also potent systemic neurotoxins that affect both the somatic and autonomic nervous systems and both the central and peripheral parts, Therefore, the signs and symptoms of acute porphyric attack reflect an extremely broad set of neurological dysfunction, which occurs secondary to the neurotoxicity of porphyrins and/or diminished intraneuronal heme levels.
When porphyria affects the nervous system, it can cause:
- chest pain
- shortness of breath
- abdominal pain
- nausea and vomiting
- muscle cramps
- muscle fasciculation
- pareses or paralysis
- head, neck, and/or back pain
- fever (autonomic system involvement)
Attacks of porphyria can develop over hours or days and last for days or weeks. Clinical diagnosis of acute porphyria is best confirmed with urine and stool tests for porphobilinogen (PBG), amniolevulinic acid (ALA), and other porphyrins. Subsequent enzyme deficiency testing and DNA testing can confirm primary genetic porphyria and the exact type of genetic porphyria. Acute porphyria attacks can be life-threatening, and treatment consists of hospitalization and infusion of Panhematin to close the open feedback loop. Glucose infusion is an adjunctive therapy only. Panhematin must be administered promptly to be effective in preventing the accumulation of porphyrins. Therefore, a STAT urinary PBG test should be administered.