Porphyria

Among the porphyrias (Greek πορφυρία, porphyria, from the purple dye ) refers to a group of metabolic disorders that are associated with a disturbance of the formation of the red blood pigment heme. This affects the enzymes of the heme biosynthesis - depending on which of the eight enzymes a defect is specific intermediates of heme synthesis accumulate in various organs and cause typical of the respective porphyria symptoms. The name " porphyria " is derived from the annular base structure of the heme, the porphyrin.

• 2.1 Acute porphyrias
• 2.2 Cutaneous porphyrias

• 3.1 Genetic clarification

• 4.1 Acute porphyrias
• 4.2 Cutaneous porphyrias

• 6.1 Literature
• 6.2 Literary processing

Forms of porphyria

There are seven forms of genetic porphyrias: The heme group ( the red blood pigment ) is built in eight steps from simple precursors, each step of a specific enzyme catalyzes (Fig. below ). Whichever of the enzymes is a reduced activity, is another metabolic product accumulates, causing the respective symptoms. It divides the Porphyrieformen based on their main symptoms in two groups, but between which there is overlap of symptoms.

The acute or acute hepatic porphyrias are associated with attacks of sudden severe abdominal pain, depending on the disease and severity occur liver problems and neurological problems. Cutaneous porphyrias show a painful sensitivity to light, also in this case the liver can be affected. Another distinction of the porphyrias in erythropoietic ( the formation of red blood cells in question ) and hepatic ( liver -related) forms refers to the education center of the heme in which the enzyme deficiency causes the most problems.

Erythropoietic porphyrias:

• Erythropoietic protoporphyria (EPP) [ E80.0 ] (Chr. 18q21.3 )
• Congenital erythropoietic porphyria ( CEP) / Günther's disease [ E80.2 ] ( Chr 10q25.3 - q26.3 )

Hepatic porphyrias:

• Porphyria cutanea tarda (PCT ) [ E80.1 ] (chromosome 1p34 ) - most common Porphyrieform the lower mold Hepatoerythropoetische porphyria ( HEP ) is a recessive, severe running form the PCT

Orthomolecular medicine claims that the Hämopyrrollaktamurie to have also called pyrroluria or kryptopyrroluria discovered, for whose existence, however, there is no evidence. The Hämopyrrollaktamurie is more psychological symptoms than the other forms.

Acquired porphyria

Poisoning eg lead, mercury and certain pesticides damaging enzymes of the heme biosynthesis and cause the same symptoms as the respective genetic porphyria.

Symptoms

Acute porphyrias

Characteristic of the relapsing course, acute crises with violent abdominal pain and sometimes light intolerance is (depending on the Porphyrieform ) Switch with often long asymptomatic phases. The acute porphyrias include the AIP, PV, HCP and the ALAD deficiency porphyria.

The following symptoms may, but do not all occur in an acute attack:

• Severe, colicky abdominal pain, often lasting for days
• Vomiting, nausea
• Pain in extremities and back
• Red coloration of the urine after prolonged exposure to air
• Neurological deficits, sometimes if mistreated irreversible
• Seizures
• Psychiatric symptoms ( psychosis )

Trigger for attacks are drugs (see below), many kinds of chemical substances, hormones ( menstrual, " pill ", stress), starvation conditions and other factors.

It is problematic, especially in undiagnosed cases that many drugs are not tolerated and lead to a worsening of the condition of the patient ( drugs lead via activation of the body's own detoxification system to increased heme synthesis, which increases the amount of heme intermediates and thus the symptoms worse ).

A list of substances classified as safe drugs can be found on the website of the European Porphyria Initiative EPI.

Since many cases are not recognized by porphyria can occur ( no morphological change in the Abdominaltraktes ) and neuropsychological failures, patients are often classified as mentally ill.

Cutaneous porphyrias

A characteristic feature is the strong, extremely painful light sensitivity of the skin to mainly visible light at 406 nm ( Soret band ), which leads to some massive and disfiguring skin and tissue damage in the cutaneous (skin -related ) porphyrias. Porphyrieformen with sun and light intolerance are CEP, HEP, PCT, HCP, PV and EPP.

Symptoms, depending on the Porphyrieform:

• Scarring, tissue death and disfigurement (loss of nose, lips, ears, fingers parts, etc. ) (CEP, HEP )
• Incorporation of the porphyrins in the teeth ( Erythrodontie ) and bone, red autofluorescence (CEP )
• Blistering of the skin
• EPP: In early stages of sun exposure despite pain no visible changes to the skin, and later ( after 12-24 hours) redness and swelling as well as extensive burns

• Only uncovered areas of skin are affected
• The pain may begin after a few minutes in the sun, only opiates are effective
• The liver can be damaged by Porphyrineinlagerungen to liver cirrhosis.

Hereditary porphyrias are rare diseases, which usually have a complicated pattern of inheritance ( skip several generations, etc. ) and are therefore often not recognized; this represents a significant risk factor for those affected, as the disease is extremely painful and potentially life- threatening.

" Dracula symptoms ": Erythrodontie ( " blood teeth " ), photophobia ( Tagschläfer ), anemia ( paleness due to a lack of red blood pigment )

" Werewolf symptoms ": hypertrichosis (increased facial hair after healing of photodermatosis ) Erythrodontie ( " blood teeth " ), nasal and / or Fingerlosigkeit ( mutilation due to bone-cartilage tissue destruction )

Proof

The diagnosis of porphyria is via the detection of specific porphyrin precursors in blood, urine and / or stool. The different precursors are separated via high performance chromatographic method (HPLC). Porphyrinvorläufer will normally continue to be used by the body immediately, an increase suggests therefore point to a porphyria. The specific composition of the present in increased concentration precursors shows that present form of porphyria. Acute porphyrias usually show only in acute attacks increased values ​​. The detection should be performed by a specialized laboratory.

An indication of some forms of acute porphyria delivers the sometimes in the air red discoloring urine (only during / before the attacks).

An obsolete method for detecting EPP was the excitation of unbound protoporphyrin in blood with certain wavelengths of light to stimulate the intrinsic fluorescence of the porphyrin roughing stand ( Soret band ).

Genetic investigation

To assess the risk of disease for relatives and descendants, analyzes the affected gene are carried out in most cases. Is the mutation found in the gene of the patient, can the specific gene locus ( place ) test very easy on the change in family members. Genetic counseling can educate then about the ( sometimes very low ) risk of disclosure to children.

Therapy

Acute porphyrias

A causal therapy does not exist yet. The risk of relapse can be reduced by triggering substances, like most drugs, alcohol and smoking shunned and on a regular carbohydrate intake ( regular food) is respected. Should new drugs are taken, the advice of a porphyria specialist should be sought before. It should be noted that data are often outdated in popular compendia. Lists of drugs that can be safely used in accordance with the current state of knowledge in acute porphyria, can be found on the websites of porphyria centers of excellence.

Acute Porphyrieschübe can be treated symptomatically ( hemin, brand name Normosang ®, should not be confused with hematin ) by the administration of high amounts of carbohydrate (glucose) or hemin or hemin arginate.

Action: The heme group is mainly in hemoglobin (red blood pigment ) in front, but also in enzymes such as cytochrome P450, which, inter alia, in the degradation or detoxification of xenobiotics (eg drugs ) in the liver plays a role. Must propagation, for example, drugs are degraded, there is an increased need for cytochrome P450 and a positive feedback to the heme synthesis pathway. If a malfunction of the pathway but the need for heme can not be met, the positive feedback instead results in an enrichment of the metabolite, which is not implemented at the normal rate ( processed ) can be. Since Porphyrinvorläufer toxic ( poisonous) to the body, it comes to the symptoms of a relapse. Hemin arginate occupied the positive feedback point in the synthesis of heme ( it suggests to the body that a sufficient amount of heme is present), thus interrupting the shear- inducing feedback.

Some porphyrias respond to bloodletting therapies, but the anemia is amplified.

For the therapy of porphyria riboflavin is under discussion.

Cutaneous porphyrias

A causal therapy exists not yet, prevention of (sun ) light and hepatotoxic substances ( alcohol, etc.) currently is the only way to protect against an outbreak of symptoms dar. Since the symptoms triggering wavelengths are in the visible range of light, is sunscreen useless, as only a protective effect in the UV range is. The same is true for other materials ( protective films, fabrics, etc.) with a UV protection factor. But currently is a derivative of the hormone alpha -MSH in the test phase, which leads even without sun exposure on hormonal stimulation to skin tanning and scored in preliminary studies a high protective effect.

Chemistry of porphyrins

Porphyrins are a class of materials of colored molecules ( according to Greek πορφυρ [ ί ] α, porfir [ í ] a, the purple dye). The red blood cells occurring in oxygen -transporting protein hemoglobin (the red blood pigment ) as the prosthetic group heme, an iron (II ) porphyrin, which is composed of tetrapyrrole as a base. At its center is an iron ion, which is essential for the oxygen binding complexed. In disorders of heme synthesis instead arise irregularly other porphyrins, the namesake of porphyria. These porphyrins no iron ion is anchored in the nitrogen ring. Since heme is also part of many other proteins such as cytochromes or myoglobin caused this central location of the failure of the biosynthesis a plethora of very different symptoms in porphyria in the different systems: the nervous and digestive systems, internal respiration, skin and psyche.