Variegate Porphyria (Protoporphyrinogen Oxidase Deficiency)

An autosomal dominant porphyria that is due to a deficiency of protoporphyrinogen oxidase (EC 1.3.3.4) in the LIVER, the seventh enzyme in the 8-enzyme biosynthetic pathway of HEME. Clinical features include both neurological symptoms and cutaneous lesions. Patients excrete increased levels of porphyrin precursors, COPROPORPHYRINS and protoporphyrinogen.

Also Known As:

Networked: 154 relevant articles (2 outcomes, 10 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Acute Intermittent Porphyria (Porphyria, Acute)
2.	Porphyrias
3.	Hepatic Porphyrias (Hepatic Porphyria)
4.	Nephrotic Syndrome (Syndrome, Nephrotic)
5.	Kidney Diseases (Kidney Disease)

Experts

1.	Frank, J: 5 articles (02/2012 - 01/2001)
2.	Poblete-Gutiérrez, Pamela: 4 articles (03/2015 - 07/2006)
3.	Frank, Jorge: 4 articles (03/2015 - 07/2006)
4.	Ferrer, Miguel D: 4 articles (07/2013 - 01/2009)
5.	Sureda, Antoni: 4 articles (07/2013 - 01/2009)
6.	Tauler, Pedro: 4 articles (07/2013 - 01/2009)
7.	Pons, Antoni: 4 articles (07/2013 - 01/2009)
8.	Tur, Josep A: 4 articles (07/2013 - 01/2009)
9.	Meissner, Peter N: 4 articles (03/2012 - 08/2003)
10.	Hift, R J: 4 articles (08/2004 - 04/2000)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Variegate Porphyria:

1.	Heme (Haem)IBA 07/01/1981 - "This is illustrated by studies in protoporphyria and variegate porphyria, disorders in which the biochemical abnormalities indicate a defect(s) in the terminal part of the heme biosynthesis pathway. " 03/01/2012 - "It has been suggested that King George III of Great Britain suffered from the haem biosynthetic disorder, variegate porphyria. " 08/01/2004 - "Variegate porphyria (VP) is an autosomal dominant disorder associated with deficient haem synthesis. " 04/21/2004 - "This modelled transmembrane complex provides a structural explanation for the uncoupling of haem biosynthesis observed in variegate porphyria patients and in plants after inhibiting PPO." 05/01/1996 - "Variegate porphyria (VP), a low-penetrant autosomal dominant inherited disorder of haem metabolism, is characterised by photosensitivity (Fig. "
2.	heme arginateIBA 09/01/1990 - "Four patients with variegate porphyria (VP) were treated with repeated haem arginate infusions daily for 4 days and then weekly for 4 weeks. " 09/01/1990 - "Effects of haem arginate on variegate porphyria." 12/01/1988 - "Haem arginate improves hepatic oxidative metabolism in variegate porphyria." 07/01/1994 - "Effects of heme arginate on cytochrome P450-mediated metabolism of drugs in patients with variegate porphyria and in healthy men." 12/01/1988 - "1. The elimination of antipyrine was investigated before and after intravenous administration of haem arginate (3 mg haem kg-1 day-1 on three or four successive days) to six patients with variegate porphyria in remission. "
3.	coproporphyrin IIBA 07/01/1995 - "A deviating biliary protoporphyrin/coproporphyrin I ratio in one patient appeared to be a useful diagnostic index for the presence of latent variegate porphyria (or variegate porphyria in remission).(ABSTRACT TRUNCATED AT 400 WORDS)" 07/01/1995 - "In subjects with symptomatic variegate porphyria, the Enterotest showed highly aberrant porphyrin patterns, with increased protoporphyrin to coproporphyrin I ratios and, in addition, the presence of some unknown porphyrins. " 07/01/1999 - "We used HPLC with fluorometric detection to measure plasma concentrations of uroporphyrin I and III, heptacarboxyl III, hexacarboxyl III, pentacarboxyl III, and coproporphyrin I and III. We studied 245 healthy subjects, 32 patients with classical porphyria cutanea tarda (PCT), 12 patients with PCT of renal failure, 13 patients with renal failure, 8 patients with pseudoporphyria of renal failure, 3 patients with acute intermittent porphyria, 5 patients with variegate porphyria, 5 patients with hereditary coproporphyria, and 4 patients with erythropoietic protoporphyria. " 10/01/1993 - "Results showed a significant decrease (p < 0.001) of the proportion of coproporphyrin I in acute hepatic porphyria (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, porphobilinogen synthase deficiency porphyria) as compared with chronic hepatic porphyria (porphyria cutanea tarda, chronic hepatic porphyria type B and C) (13.2 +/- 5.3%, mean +/- S.D., vs. 31.4 +/- 11.5%). "
4.	Antipyrine (Phenazone)FDA Link 03/01/1992 - "Rapid normalization of antipyrine oxidation by heme in variegate porphyria." 12/01/1988 - "1. The elimination of antipyrine was investigated before and after intravenous administration of haem arginate (3 mg haem kg-1 day-1 on three or four successive days) to six patients with variegate porphyria in remission. "
5.	Protoporphyrinogen Oxidase (Protox)IBA 02/01/2002 - "Functional studies of mutations in the human protoporphyrinogen oxidase gene in variegate porphyria." 04/01/1998 - "Our study establishes the molecular basis of "homozygous" variegate porphyria for the first time, in demonstrating that this patient is a compound heterozygote for two different missense mutations in the protoporphyrinogen oxidase gene." 05/01/2015 - "She was biochemically diagnosed with variegate porphyria, and mutational analysis confirmed the presence of a heterozygous mutation in the protoporphyrinogen oxidase gene. " 04/26/2013 - "Defects in the human protoporphyrinogen oxidase (hPPO) gene, resulting in ~50% decreased activity of hPPO, is responsible for the dominantly inherited disorder variegate porphyria (VP). " 01/01/2013 - "Partial protoporphyrinogen oxidase (PPOX) gene deletions, due to different Alu-mediated mechanisms, identified by MLPA analysis in patients with variegate porphyria."
6.	PorphyrinsIBA 01/01/1969 - "Preliminary studies on bile porphyrins in the quiescent phase of variegate porphyria." 08/01/2001 - "Chromatographic analysis of urinary porphyrins was compatible with variegate porphyria. " 11/01/1995 - "Excretion of porphyrins, especially protoporphyrin and X-porphyrin in the feces were markedly increased, and the diagnosis of variegate porphyria was made. " 07/14/1995 - "Variegate porphyria: diagnostic value of fluorometric scanning of plasma porphyrins." 05/16/1991 - "Since elevated fecal porphyrin levels in variegate porphyria are presumably a consequence of increased biliary excretion, we evaluated whether analysis of porphyrins in bile distinguishes better between patients with variegate porphyria and controls. "
7.	Hydroxymethylbilane Synthase (Porphobilinogen Deaminase)IBA 10/01/2001 - "Variegate porphyria with coexistent decrease in porphobilinogen deaminase activity." 06/01/1986 - "Mean porphobilinogen deaminase activity in the erythrocytes of twenty-one patients with variegate porphyria was 8.37 +/- 1.99 nmol of uroporphyrin 1 erythrocytes-1 s-1, a 28% reduction (P less than 0.001) from normal (11.98 +/- 2.11). " 10/01/2001 - "Biochemical analysis revealed that most of the family members, though free of clinical symptoms, excrete porphyrin metabolites in urine and stool similar to variegate porphyria, accompanied by a significant decrease of porphobilinogen deaminase activity of a range which is ordinarily found in patients with acute intermittent porphyria only (approximately 50%). " 06/01/1986 - "Protoporphyrinogen oxidase and porphobilinogen deaminase in variegate porphyria." 03/01/2015 - "Variegate porphyria (VP) and acute intermittent porphyria (AIP), the two most common types of acute porphyrias (AHPs), result from a partial deficiency of protoporphyrinogen oxidase (PPOX) and hydroxymethylbilane synthase (HMBS), respectively. "
8.	EnzymesIBA 02/01/1997 - "Three variegate porphyria mutant PPO enzymes were expressed and characterized. " 06/01/1986 - "The reduced activities of these two enzymes comply with the expression of variegate porphyria during its quiescent and acute phases." 06/01/1986 - "Two enzymes of the haem biosynthetic pathway were investigated in patients with variegate porphyria. " 10/21/1989 - "To test this hypothesis the enzymes responsible for these conditions, protoporphyrinogen oxidase (variegate porphyria) and uroporphyrinogen decarboxylase (porphyria cutanea tarda) were measured in vitro in haemolysates and lymphoblasts of 10 subjects with dual porphyria in order to clarify the enzymatic defects. " 10/12/1985 - "Studies of the enzymes of haem biosynthesis in peripheral blood cells showed a dual enzyme deficiency, with reduced activity of both porphobilinogen deaminase, as seen in acute intermittent porphyria, and protoporphyrinogen oxidase, as seen in variegate porphyria. "
9.	Nonsense Codon (Nonsense Mutation)IBA 04/01/1998 - "In this study, we identified the first nonsense mutation in a family with variegate porphyria. " 04/01/1998 - "Our investigation establishes that a nonsense mutation in the protoporphyrinogen oxidase gene is the underlying mutation in this family with variegate porphyria." 04/01/1998 - "Variegate porphyria: identification of a nonsense mutation in the protoporphyrinogen oxidase gene."
10.	Reactive Oxygen Species (Oxygen Radicals)IBA 06/01/2010 - "This study aimed to analyse lymphocyte reactive oxygen species (ROS) production and detoxification mechanisms and the appearance of oxidative damage in variegate porphyria (VP) patients. " 06/01/2010 - "Impaired lymphocyte mitochondrial antioxidant defences in variegate porphyria are accompanied by more inducible reactive oxygen species production and DNA damage."

Therapies and Procedures

1.	Renal Dialysis (Hemodialysis) 04/01/1986 - "Porphyria cutanea tarda, the most common disorder of porphyrin metabolism, must be differentiated from variegate porphyria, hereditary coproporphyria, bullous dermatosis of hemodialysis, and drug-related pseudoporphyria." 09/01/2010 - "The objectives of this study were as follows: (1) to evaluate the plasma and erythrocyte VB(6) (effect of PLP; effect of PLP was in indirect relationship with the concentration of erythrocyte VB(6)), and plasma and urinary OA in marathon runners, in patients with acute intermittent porphyria (AIP) and variegate porphyria, and in patients with stage 1 chronic kidney disease (CKD), chronic glomerulonephritis and nephrotic syndrome (CGNS); (2) to examine the influence of water diuresis in healthy subjects, and the influence of sodium diuresis (high sodium intake) and an intravenous administration of furosemide on the urinary excretion of VB(6) and OA in CKD stage 3-4 patients; and (3) to evaluate the influence of erythropoietin treatment on erythrocyte VB(6) (effect of PLP) in hemodialysis (HD) patients, and the influence of continuous ambulatory peritoneal dialysis (CAPD) therapy on plasma VB(6) and OA and their peritoneal clearance and transfer. "
2.	Continuous Ambulatory Peritoneal Dialysis (CAPD) 09/01/2010 - "A combination of 29 marathon runners, 15 patients with CG and NS, 11 patients with AIP, 1 patient with variegate porphyria, 15 healthy subjects, 27 CKD stage 3-4 patients, 30 HD, and 27 CAPD patients were used in the study. " 09/01/2010 - "The objectives of this study were as follows: (1) to evaluate the plasma and erythrocyte VB(6) (effect of PLP; effect of PLP was in indirect relationship with the concentration of erythrocyte VB(6)), and plasma and urinary OA in marathon runners, in patients with acute intermittent porphyria (AIP) and variegate porphyria, and in patients with stage 1 chronic kidney disease (CKD), chronic glomerulonephritis and nephrotic syndrome (CGNS); (2) to examine the influence of water diuresis in healthy subjects, and the influence of sodium diuresis (high sodium intake) and an intravenous administration of furosemide on the urinary excretion of VB(6) and OA in CKD stage 3-4 patients; and (3) to evaluate the influence of erythropoietin treatment on erythrocyte VB(6) (effect of PLP) in hemodialysis (HD) patients, and the influence of continuous ambulatory peritoneal dialysis (CAPD) therapy on plasma VB(6) and OA and their peritoneal clearance and transfer. "
3.	Anesthesia 09/01/1993 - "[Anesthesia in variegate porphyria]." 07/01/1980 - "To evaluate the risk of inducing acute symptoms after general anesthesia in patients with "inducible " porphyrias, the authors analyzed retrospectively the effects of 78 exposure to anesthesia in 47 patients, 33 with acute intermittent porphyria and 14 with variegate porphyria. "
4.	Transplants (Transplant) 01/01/1982 - "The pre- and postoperative porphyrin status of a unique patient with variegate porphyria who received a successful renal transplant implies that the excess urinary porphyrins and precursors excreted in the acute porphyrias are also of mainly renal, as opposed to hepatic origin. "
5.	Liver Transplantation 07/01/2004 - "A case of liver transplantation is described with a recovery from a variegate porphyria. " 07/01/2004 - "Recovery from a variegate porphyria by a liver transplantation."