Porphyrins, Porphobilinogen
Sample
- Collect fresh urine.
- Random urine can be used.
- Protect the sample from light.
- Add 5 g Na2CO3.
- Store the sample at 4 to 8 °C.
Purpose of the test (Indications)
- This test will quantitate porphyrins and porphobilinogen.
- This can be used to find various forms of porphyria.
Definition
- The porphyrias are a group of disorders characterized by a deficiency of or defect in the enzymes involved in porphyrins metabolism and heme synthesis.
Pathophysiology
- The term “porphyria” is derived from the Greek word porphyria, meaning “purple pigment.”
- A porphyria is a group of disorders that result in an accumulation of chemicals called porphyrins in the body.
- This is a group of genetic abnormality with associated enzyme deficiency involved in the porphyrin synthesis or metabolism.’
- The porphyrins are building blocks in the synthesis of heme.
- Porphyrins are a byproduct of heme synthesis.
- Porphyrins are the main precursors of heme, an essential constituent of hemoglobin, myoglobin, catalase, peroxidase, respiratory, and P450 liver cytochromes.
- Accumulation of porphyrins, the heme precursors, is toxic to tissue in high concentrations.
- The primary porphyrins of RBC are :
- Protoporphyrin.
- Uroporphyrin.
- Coproporphyrin.
- The primary porphyrins of RBC are :
- Then heme combine with globin in the RBC, and hemoglobin is formed.
- Porphyrias are classified according to the location of the accumulation of porphyrins and precursors.
- In most porphyrias, there is an increased level of porphyrins and porphobilinogen in the urine.
- Classification of porphyrias:
- Symptomatically, acute porphyrias.
- Primarily present with nervous system involvement.
- Often with severe abdominal pain, vomiting.
- Neuropathy and mental disturbances.
- Cutaneous porphyrias present with :
- Skin manifestations often after exposure to the sun due to the accumulation of excess porphyrins near the skin’s surface.
- Physiological classification is based on the accumulation of heme precursors, either in the liver or bone marrow and red blood cells.
- Hepatic porphyria has S/S of :
- Acute neurological attacks (seizures, psychosis).
- Extreme back and abdominal pain.
- Acute polyneuropathy.
- Erythropoietic porphyria has S/S of :
- Skin problems, usually a light-sensitive blistering rash and increased hair growth.
- Hepatic porphyria has S/S of :
- Erythropoietic porphyria shows the following signs and symptoms :
- Photosensitivity of eyes and skin.
- Symptomatically, acute porphyrias.
- Classification of porphyrias:
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Clinical classification:
- Porphyria that produces skin manifestation without the presence of neurological symptoms are:
- Porphyria cutanea tarda.
- Congenital erythropoietic porphyria.
- Erythropoietic porphyria.
- Porphyria that is manifested by neurological symptoms (cutaneous symptoms are absent) are:
- Acute intermittent porphyria.
- Porphyria that has both cutaneous and neurological manifestations are:
- Hereditary coproporphyria.
- Variegate porphyria.
- Porphyria that produces skin manifestation without the presence of neurological symptoms are:
Excretion of Porphyrins:
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- Aminolevulinic acid and porphobilinogens are excreted in the urine.
- Uroporphyrins are also excreted in the urine, and a minimal amount is excreted in the feces.
- Most of the coproporphyrins are eliminated in the feces and a small amount in the urine.
- Protoporphyrins are eliminated through bile, and the average fecal content is 1 mg/day.
- Coproporphyrins’ urinary excretion is increased in obstructive jaundice, liver diseases, lead poisoning, and hemolytic anemias.
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Disease | Substrate | Enzyme deficiency |
Acute Intermittent Porphyria | Porphobilinogen | Hydroxymethylbilane synthase |
Porphyria Cutanea Tarda | Uroporphyrinogen III | Uroporphyrinogen decarboxylase |
Hereditary coproporphyria | Coproporphyrinogen III | Coproporphyrinogen Oxidase |
Erythropoietic Protoporphyria | protoporphyrin | Ferrochelata |
Signs and Symptoms
- The following factors may initiate an acute attack:
- Some of the drugs.
- Smoking may initiate the attack.
- Use of alcohol.
- By some surgical procedures.
- Emotional upset.
- In females by the menstrual cycle.
- In females during pregnancy.
- Some time infection may give rise to attack.
- The acute attack may start with anxiety, restlessness, and difficulty in sleeping.
- The patient may develop a painful abdomen, and this may be very severe.
- There may be nausea and vomiting.
- The patient may develop constipation.
- There may be tachycardia and hypertension.
- Urine is dark or reddish.
- Rarely there may be sudden death, which may be due to cardiac arrhythmias.
Normal
Source 1
Porphobilinogen
- Fresh urine or 24 hours sample = Negative
- Spectrophotometric method (24 hours of urine)
- <2.0 mg/L
- <3.4 mg/day
- ≤2.0 mg/day
- To convert into SI unit x 4.42 = µmol/L
Porphyrins
- Urine fresh random = Negative
- Total porphyrin (whole blood) = <60 µg/dL
Total porphyrins
- 20 to 320 nmol/L (urine)
Uroporphyrin fraction = <33 µg/24 hours urine
= 17 to 52 µg/24 hours urine
Coproporphyrins fraction = <183 µg/24 hours urine
= <294 µg/24 hours urine
= 52 to 163 µg/24 hours urine
Source 2
Urine 24 hours or fresh:
- Negative or trace.
- Total porphyrin:
- Male = 8 to 149 mcg/24 hours of the urine
- Female = 3 to 78 mcg/24 hours of the urine
- Uroporphyrin:
- Male = 4 to 46 mcg/24 hours of urine
- Female = 3 to 22 mcg/24 hours of the urine
- Coproporphyrin:
- Male = <96 mcg/24 hours of the urine
- Female = <60 mcg/24 hours of the urine
- Porphobilinogen = 0 to 2 mg /24 hours of the urine
- another source <1 mg/24 hour of the urine
- δ-Aminolevulinic acid = 1.5 to 7.5 mg/day of the urine
Source 4
- Porphobilinogen
- Random specimen = 0 to 2.0 mg/L
- 24 hours sample = 0 to 1.5 mg/24 hours
- Δ-aminolevulinic acid
- Random specimen = 0. to 4.5 mg/L
- 24 hour specimen = 1.5 to 7.5 mg/24 hours
Test | µg/24 hours Urine | |
Male | Female | |
Random sample | Negative | Negative |
Uroporphyrin | 8 to 44 | 4 to 22 |
Coproporphyrin | 10 to 109 | 3 to 56 |
Heptacarboxyporphyrin | 0 to 12 | 0 to 9 |
Pentacarboxy porphyrin | 0 to 4 | o to 3 |
Hexacarboxyporphyrin | 0 to 5 | 0 to 5 |
Diagnosis
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- A urine sample is not as accurate as the plasma concentration.
- Urine is suitable as a screening test for porphyria.
- A urine sample is not as accurate as the plasma concentration.
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Treatment
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- Treat to relieve the symptoms.
- Drug-like heme arginate is given to stop the process.
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