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Porphyria

The heme biosynthetic pathway consists of 8 enzymes. The formation of heme begins with the condensation of glycine and cialis professional canadian canada succinyl coenzyme A to delta-aminolevulinic acid (ALA). A series of www.puertohuelva.com enzyme reactions converts ALA to porphobilinogen (PBG) and then to various porphyrinogens. Finally, iron is inserted into protoporphyrin by the enzyme ferrochelatase, forming heme.

The majority of heme is produced in erythropoietic cells where it is natural viagra incorporated into hemoglobin. Hepatocytes also produce a significant amount for use in myoglobin, cytochromes, catalase and peroxidase. Each porphyria is caused by a specific enzyme deficiency involved in the heme biosynthetic pathway.

Most types of porphyria, with the exception of congenital erythropoietic porphyria, are diagnosed in adulthood. The simplest approach to classifying the porphyrias is on the generic viagra australia basis of their clinical manifestations. Porphyrias can be divided into two general groups; those causing predominantly acute neurologic attacks and those causing chronic cutaneous photosensitivity.

Neurologic Disease

Cutaneous Disease

Acute Intermittent Porphyria (AlP)

Porphyria Cutanea Tarda (PCT)

Variegate Porphyria (VP)

Congenital Erythropoietic Porphyria (CEP)

Hereditary coproporphyria (HCP)

Hepatoerythropoietic porphyria (HEP)

Delta aminolevulinic acid dehydratase deficiency (ALA)

Erythropoietic protoporphyria (EPP)

 

Chronic Cutaneous Porphyrias

The most common causes of chronic cutaneous photosensitivity are PCT, CEP, HEP, and EPP. A few of the acute neurologic porphyrias, such as VP, may express photosensitivity in addition to neurologic symptoms. Cutaneous photosensitivity is due to the accumulation of canadian phamacy excessive amounts of porphyrins in the skin.

PCT is the most common porphyria and most responsive to treatment. Approximately 75% of cases are acquired and 25% are inherited. Acquired cases are precipitated by complications from hepatitis C, hemochromatosis, alcohol abuse, iron overload, smoking, estrogen therapy and occupational exposure to buy original viagra polychlorinated cyclic hydrocarbons. Familial PCT is caused by partial deficiency of uroporphyrinogen decarboxylase. It is characterized by photosensitivity and skin fragility. Sun exposed skin is most often affected. Hypertrichosis, hyperpigmentation, or alopecia may be observed. Liver function tests are usually abnormal as a result of uroporphyrinogen accumulation in the liver. PCT is diagnosed by demonstrating elevated uroporphyrin and http://www.leksikon.me/cost-of-levitra heptacarboxylporphyrinogen in urine. Sporadic versus familial PCT can be distinguished by measuring uroporphyrinogen decarboxylase levels in erythrocytes.

EPP is the third most common porphyria. It is caused by an autosomal dominant disorder with reduced penetrance due to deficiency of the enzyme ferrochelatase. Only about 10% of individuals with this deficiency develop clinical symptoms. Onset usually occurs before age 10. Sun exposure causes painful erythema, edema and itching. Blistering and scarring are less common than in the other cutaneous porphyrias. Patients have an increased risk of hemolytic anemia. Gallstone formation is common. Liver dysfunction is seen in 20% of patients. When ferrochelatase is order propica deficient, protoporphyrin accumulates in erythrocytes, diffuses into plasma, is cleared by the liver, and secreted into bile. Excess protoporphyrin levels are detected in erythrocytes (free erythrocyte protoporphyrin) and in feces, but urine levels are not elevated because protoporphyrin is not soluble in water. The tests of choice are total porphyrins and protoporphyrin fractionation in erythrocytes. Erythrocyte protoporphyrin levels in affected patients are >200 ug/dL , compared to <60 ug/dL in normal patients.

HEP is a rare but severe porphyria due to markedly deficient uroporphyrinogen decarboxylase activity. Onset usually occurs in infancy or childhood. Patients have severe photosensitivity leading to blistering and scarring. Hemolytic anemia and hepatosplenomegaly may also be present.

CEP, also known as Gunther’s Disease, is a very rare and severe disease that causes mutilating photodermatitis and viagra sales hong kong excretion of dark red urine early in life. Most patients present in infancy with photosensitivity, blistering, erythrodontia and hypertrichosis. Scarring and mutilation may be seen. CEP may cause hemolytic anemia and the newborn and may cause nonimmune hydrops fetalis. It is an autosomal recessive disorder caused by a deficiency of the erythrocyte enzyme, uroporphyrinogen III (UPG III) cosynthase, which results in the accumulation of an abnormal uroporphyrinogen I isomer. It is oxidized to uroporphyrin and excreted into the urine. Urine, erythrocyte and fecal porphyrins are elevated. Porphyrins in the urine are predominantly the I series isomers of http://www.puertohuelva.com/viagra-professional-canada uroporphyrin and coproporphyrin. Erythrocyte porphyrins consist predominantly of uroporphyrin I. Coproporphyrin I is detected in feces. Demonstrating diminished erythrocyte uroporphyrinogen III (UPG III) cosynthase,enzyme activity confirms the buy viagra with pay pal diagnosis.

 

Porphyria

Enzyme

Urine

Feces

Erythrocytes

Plasma

PCT

UPG

decarboxylase

Uroporphyrin

Heptacarboxyl

Uro

HEP

UPG

decarboxylase

Uroporphyrin

Heptacarboxyl

Zinc proto

Uro

CEP

UPG synthase

Uroporphyrin

Copro

UroporphyrinI

Copro I

Uroporphyrin,

Coproporphyrin

Uro

Copro I

EPP

Ferrochelatase

Proto

Free Proto

Proto

ALAD

ALA dehyratase

ALA

AIP

PG deaminase

ALA, PBG, Uro,

Copro

Increased porphyrin during episodes

HCP

CPG oxidase

Copro, ALA, PBG

Copro III/I ratio

Copro

VP

Protoporphyrinogen oxidase

Copro, PBG, ALA,

Proto >Coproporphyrin

 

Acute Neurologic Porphyrias

AIP, HCP, VP and ALA are the most prevalent forms of acute neurologic porphyria and are characterized by acute episodic attacks of severe abdominal pain and psychiatric distress. Other symptoms include hypertension, paresthesias, seizures, and fever. Neuromuscular weakness can progress rapidly to paralysis and respiratory failure. Acute attacks are provoked by medications, such as barbiturates and cialis generic 100 mg antibiotics. Industrial or household chemicals, industrial chemical wastes, agricultural pesticides, garden chemicals, automotive degreasing solvents, and ceramic mineral pigments can also induce them.

AlP is the second most common porphyria and is inherited as an autosomal dominant trait with reduced penetranceAIP rarely presents prior to puberty, with onset most commonly between ages 20 and 40. It is aptly named for the intermittent episodes in which patients experience acute neuropathic symptoms. Episodes are highly variable, and although acute in duration, may last from days to several months. Patients experience episodes of severe abdominal pain, often in conjunction with nausea, vomiting and constipation. Peripheral neuropathy is common, but seldom occurs in the absence of abdominal pain. Psychiatric symptoms include psychotic episodes, depression and anxiety. Hypertension and tachycardia may be observed. Acute episodes may be life threatening due to seizures and respiratory paralysis.

AIP is caused by a deficiency of the enzyme porphobilinogen deaminase (PBGD), also called uroporphyrinogen I synthase. Only 20% of individuals with this deficiency will become symptomatic during their lifetime. Because of this deficiency, porphobilinogen cannot be assembled into the linear tetrapyrroles that ultimately form uroporphyrin. During acute episodes, PBG and ALA are excreted in excess amounts into the urine. During latent stages, urine porphyrin precursor levels are within normal limits and erythrocyte PBG deaminase must be measured.

VP is an autosomal dominant acute porphyria that causes abdominal pain, vomiting, neuropathies and psychiatric sequelae. Cutaneous photosensitivity and sensitivity to viagra 100 mg price mechanical trauma are more pronounced than in the other acute porphyrias. Neuropathic symptoms occur only during acute crisis, but photosensitivity remains a chronic symptom. VP is caused by a deficiency of protoporphyrinogen oxidase, which is the next to the last enzyme involved in heme synthesis. Diagnosis of http://masscop.org/cheap-cialis-on-line VP relies upon porphyrin analysis in urine and it's great! feces. Both fecal protoporphyrin (predominant) & coproporpyrins are increased.

HCP is an autosomal dominant disorder that is one of the rarest forms of porphyria. Symptoms very rarely present before puberty. Clinical manifestations are predominantly neurovisceral. About one third of cases exhibit photosensitivity similar to PCT and VP. Patients without dermatologic findings are clinically indistinguishable from patients with AIP and VP. HCP is due to a deficiency of coproporphyrinogen (CPG) oxidase. A laboratory test for this enzyme deficiency is not available. The biochemical hallmark is http://www.shoreacres.net/cost-of-levitra elevated excretion of coproporphyrin in urine and feces. Fecal porphyrin analysis allows for distinction between HCP from VP and AIP.

ALAD deficiency porphyria is a very rare, autosomal recessive form of acute porphyrias. Clinical manifestations are predominantly neuropathic and include abdominal pain, vomiting, and pain in the extremities. ALAD is differentiated from other acute porphyrias by normal urinary PBG in the presence of significantly elevated ALA and markedly decreased (<5%) ALAD enzyme activity. Lead intoxication can also produce elevated ALA with normal PBG, so whole blood lead analysis should also be performed to rule out this possibility.

Suspected Porphyria

Recommended First Tests

Unknown type

Urine Porphyrins quantitation, 24 hour

Acute porphyrias

AIP

Urine Porphyrins quantitation, 24 hour

Urine ALA, 24 hour

Urine porphobilinogen, random

Erythrocyte porphobilinogen deaminase

VP

Urine Porphyrins quantitation, 24 hour

Urine ALA, 24 hour

Urine porphobilinogen, random

HCP

Urine Porphyrins quantitation, 24 hour

Urine ALA, 24 hour

Urine porphobilinogen, random

ALAD

Urine Porphyrins quantitation, 24 hour

Urine ALA, 24 hour

Erythrocyte ALA dehydratase

Cutaneous porphyrias

PCT

Urine Porphyrins quantitation, 24 hour

Plasma Porphyrins fractionation

EPP

Erythrocyte Porphyrins, total

CEP

Erythrocyte Porphyrins, total

Specimen requirements: ALA quantitation requires a 24 hour urine collected in a container with 25 mL of 50% acetic acid. Urine porphyrins require a 24 urine collected in a container with 5g of sodium carbonate. PBG is included in quantitative urine porphyrins. Fecal porphyrins require 100g of feces collected over a 48 to 96 hour period. Erythrocyte porphyrins and enzyme activity measurements require one green top tube of blood.

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