Porphyrins, Quantitative, 24-Hour Urine

Porphyrins, Quantitative, 24-Hour Urine

Number

003194

CPT

84120

Related Information

Porphyrins, Quantitative, Random Urine

Urine Testing: Preservative Quick Reference Chart

Synonyms

Coproporphyrin ; Uroporphyrin

Test Includes

Coproporphyrins I and III; uroporphyrins; heptacarboxylporphyrins; hexacarboxylporphyrins; pentacarboxylporphyrins

Special Instructions

The request form must state 24-hour collection volume.

Specimen

Urine (24-hour), protected from light

Volume

2 mL aliquot

Minimum Volume

1.5 mL aliquot

Container

Amber plastic urine container with 5 g/L sodium carbonate (Na₂CO₃) as the preferred preservative. No preservative is also acceptable. Do not use acid preservative. Use amber plastic urine cup and amber-top; order LabCorp N^o 20656. (If amber cups are unavailable, cover plastic container completely, top and bottom, with aluminum foil. Identify specimen with patient name directly on the container and on the outside of the aluminum foil. Secure with tape.)

Collection

Instruct patient to void at 8 AM (or 8 PM) and discard the specimen. Then collect all the urine including the final specimen voided at the end of the 24-hour collection period (ie, 8 AM (or 8 PM) the following day). Specimen must be kept refrigerated during collection. Label container with patient's name, and date and time collection started and finished. Measure and record total urine volume. Mix well; send aliquot to laboratory.

Storage Instructions

Refrigerate. Do not expose to light.

Causes for Rejection

Stored specimen not refrigerated; specimen exposed to light; acid preservative; pH <3

Reference Interval

Coproporphyrin I: 0-24 μg/24 hours
Coproporphyrin III: 0-74 μg/24 hours
Heptacarboxylporphyrins: 0-4 μg/24 hours
Hexacarboxylporphyrins: 0-1 μg/24 hours
Pentacarboxylporphyrins: 0-4 μg/24 hours
Uroporphyrins: 0-2 μg/24 hours

See table.

Pattern of the Different Porphyrias

Disease	Uro	Hepta	Hexa	Penta	Copro I	Copro III
Porphyria cutanea tarda	++	++	+	+	+*	+*
Acute intermittent porphyria	++	+	+	++	+*	++*
Porphyria variegata	++	+	+	++	+*	++*
Hereditary coproporphyria	+	+	+	++	n*	++*
Protoporphyria	v	n	n	v	+*	v
Morbus Gunther	++	+	+	+	++**
Porphobilinogen synthase deficiency	+	+	+	++		++
+ = increased; ++ = strongly increased; n = normal; v = varies.
Values from: Doss M, “Porphyrinstoffwechsel,” Lehrbuch der Klinischen Chemie und Pathobiochemie, Greiling H and Gressner AM (Hrsg), 3, Auflage, Schattauer Verlag Stuttgard New York.
Values maked with * and ** respectively, are derived from:
Hindmarsh JT, Oliveras L, and Greenway DC, “Biochemical Differentiation of the Porphyrias,” Clin Biochem*, 1999, 32:609-19.
*Elder GH, Smith SG, and Smyth SJ, “Laboratory Investigation of the Porphyrias,” Clin Biochem*, 1990, 27:395-412.

Use

Evaluate porphyrias, including those involving deficiencies of enzymes which are needed for heme synthesis and chemical porphyrias.

In congenital erythropoietic porphyria, elevations of urinary uroporphyrin and coproporphyrin occur, with the former exceeding the latter.

In acute intermittent porphyria, porphobilinogen and delta aminolevulinic acid are elevated in acute attacks, and mild increases of urinary uroporphyrin and coproporphyrin may be found. Porphobilinogen is increased in many but not all patients with acute intermittent porphyria in latent periods. Quantitative porphobilinogen is a better test than delta aminolevulinic acid overall for acute intermittent porphyria, but both are used (as well as the Watson-Schwartz test).¹

Coproporphyrin and porphobilinogen excretion in urine are markedly increased during acute attacks of hereditary coproporphyria, increase of urinary uroporphyrin may be found, and increased fecal coproporphyrin III is described.

In variegate porphyria in acute attacks, results are similar to those of acute intermittent porphyria. Porphobilinogen and ALA are prone to become normal between attacks. Urine coproporphyrin exceeds uroporphyrin excretion during acute attacks.

Chemical porphyrias occur. Porphyrinogenic chemicals include certain halogenated hydrocarbons which cause the excretion of increased uroporphyrin.

In lead poisoning elevation of delta aminolevulinic acid greater than that of porphobilinogen occurs and porphobilinogen may be normal. Urinary coproporphyrin characteristically is increased. Free erythrocyte protoporphyrin is increased. Toxins such as lead interfere with heme synthesis and cause porphyrinuria.

Increased urine excretion of uroporphyrinogen, uroporphyrin, and coproporphyrin occurs in porphyria cutanea tarda. It is found in middle-aged men who like ethanol, young women on oral contraceptives, and in subjects on dialysis. These patients do not excrete increased porphobilinogen, but may have slight elevations of delta aminolevulinic acid.

Limitations

Increased porphobilinogen may occur in patients on oral contraceptives. This test and delta aminolevulinic acid will not detect protoporphyria. Coproporphyrinuria alone lacks specificity and sensitivity for lead testing. Erythrocyte uroporphyrinogen-I-synthase is decreased in latent acute intermittent porphyria, and is needed in patients with possible latent acute intermittent porphyria. Quantitative porphobilinogen is of value in active and in many cases of latent acute intermittent porphyria, but will miss some of the latter when compared to red cell uroporphyrinogen-I-synthase.

Methodology

High-pressure liquid chromatography (HPLC) with fluorometric detection

Additional Information

Increased urine porphyrin excretion may be secondary to other diseases (eg, hepatobiliary diseases), especially coproporphyrin excretion. These are secondary porphyrinurias. They lack increased urinary porphobilinogen or Δ-ALA, with the important exception of lead poisoning.² The table provides an abbreviated overview of the porphyrias. Porphyrin fractionation of plasma can be done. Increases of urine porphyrins are found with congenital erythropoietic porphyria, acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria cutanea tarda. Porphyrias: Overview

Disorder	Inheritance	Age of Clinical Onset	Primary Organ Involvement	Useful Tests	Primary Symptoms
Congenital erythropoietic porphyria	Autosomal recessive	Birth – 5 y	Erythroid cells	Urinary porphyrins Fecal porphyrins Uroporphyrinogen III synthase, erythrocytes	Severe photosensitivity
(Günther disease)	Rare			Fluorescence of a diaper under Wood light	Red urine Stains diapers Hemolytic anemia
Acute intermittent porphyria	Autosomal dominant	Adults	Hepatic, probably erythroid cells	Urine porphobilinogen Porphobilinogen deaminase, erythrocyte Urine porphyrins Urinary delta aminolevulinic acid Erythrocyte uroporphyrinogen 1 synthase Fecal porphyrins	Mild / severe neurologic / visceral (autonomic) symptoms
Precipitating causes include barbiturates, hydantoins, sulfonamides	Most common acute hepatic porphyria in U.S.				Acute attacks
Hereditary coproporphyria	Autosomal dominant	Adults	Hepatic, possibly erythroid cells	Urine PBG and ALA in acute attacks Urine porphyrins including coproporphyrin Fecal porphyrins Plasma porphyrins	Similar to variegate porphyria Acute attacks
Variegate porphyria	Autosomal dominant	Adults	Hepatic, possibly erythroid cells	Urine PBG and ALA in acute attacks Urine porphyrins Fecal porphyrins Plasma porphyrins Erythrocyte uroporphyrinogen-1-synthase	Mild / severe photosensitivity, neurologic / visceral symptoms Acute attacks
Porphyria cutanea tarda	Autosomal dominant, type II (inherited type); sporadic type also known; most common porphyria in U.S.	Adults	Hepatic, possibly erythroid cells; photosensitivity	Urine porphyrins Plasma porphyrins Uroporphyrinogen decarboxylase, type II (RBCs)	Similar to variegate porphyria Photosensitization Liver damage
Protoporphyria	Autosomal dominant	Usually childhood	Erythroid cells, probably liver	Protoporphyrin, free erythrocyte	Photosensitization Liver damage
Acquired (intoxication) porphyria	Acquired	Children and adults	Hepatic, erythroid cells	Erythrocyte porphyrins Urinary delta aminolevulinic acid Urine porphobilinogen Urine porphyrins Fecal porphyrins	Mild photosensitivity

Fecal porphyrin examination for hereditary coproporphyria, variegate porphyria, and protoporphyria can be used for adult patients. Stool examination for coproporphyrin and protoporphyrin is recommended for diagnosis of variegate porphyria.³

Neurologic dysfunction occurs in the hepatic porphyrias, the types of porphyria in which acute attacks develop: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and ALA dehydrase deficiency. Abdominal pain, caused by autonomic neuropathy, occurs with acute attacks (eg, acute intermittent porphyria). It is the most common symptom of acute intermittent porphyria.²

Cutaneous aspects of the porphyrias are caused by photosensitization (eg, porphyria cutanea tarda, protoporphyria).

Hepatic complications are found with porphyria cutanea tarda and protoporphyria. Fluorescence is demonstrable in liver biopsies from patients with the former, as well as siderosis. Crystalline deposits may be found in protoporphyria.² The amount of porphobilinogen excreted in acute intermittent porphyria is usually greater than the excretion of delta aminolevulinic acid (Δ-ALA). When there is more Δ-ALA, another diagnosis should be considered, including lead poisoning, another type of porphyria, or hereditary tyrosinemia.² See also Protoporphyrin, Free Erythrocyte, and Zinc Protoporphyrin [010165] , which pertains to lead poisoning, and erythropoietic protoporphyria. The differential diagnosis of lead poisoning is relevant.⁴

Footnotes

Tschudy DP, “Porphyrins,” Chemical Diagnosis and Disease, Brown SS, Mitchell FL, and Young DS, eds, Amsterdam, Holland: Elsevier/North Holland Biomedical Press, 1979, 1039-58.
Bloomer JR and Bonkovsky HL, “The Porphyrias,” Dis Mon, 1989, 35(1):1-54.
Muhlbauer JE, Pathak MA, Tishler PV, et al, “Variegate Porphyria in New England,” JAMA, 1982, 247(22):3095-102.
Bird TD, Wallace DM, and Labbe RF, “The Porphyria, Plumbism, Pottery Puzzle,” JAMA, 1982, 247(6):813-4