Variegate porphyria

Variegate porphyria
Synonyms	Mixed hepatic porphyria,<ref name="Andrews" /> Mixed porphyria,<ref name="Andrews" /> South African genetic porphyria,<ref name="Andrews">, Andrews' Diseases of the Skin: clinical Dermatology, Saunders Elsevier, 2006, ISBN 978-0-7216-2921-6,</ref> and South African porphyria.<ref name="Bolognia">, Dermatology: 2-Volume Set, St. Louis:Mosby, 2007, ISBN 978-1-4160-2999-1,</ref>
Pronounce
Field
Symptoms	skin problems, Enzyme difficiency.
Complications
Onset
Duration
Types
Causes	genetic mutations.
Risks
Diagnosis
Differential diagnosis
Prevention
Treatment	liver transplants.
Medication
Prognosis
Frequency
Deaths

Variegate porphyria, also known by several other names, is an autosomal dominant porphyria<ref>"porphyria variegata" at Dorland's Medical Dictionary </ref> that can have acute (severe but usually not long-lasting) symptoms along with symptoms that affect the skin. The disorder results from low levels of the enzyme responsible for the seventh step in heme production. Heme is a vital molecule for all of the body's organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood.

Signs and symptoms

When symptoms occur, they can include acute attacks (similar to acute intermittent porphyria) or skin damage. Acute attacks usually begin in adulthood and cause abdominal pain, vomiting, diarrhoea and constipation. During an attack, a person may also experience muscle weakness, seizures, and mental changes such as anxiety and hallucinations. These signs and symptoms are triggered by nongenetic factors such as certain drugs, dieting or fasting, certain hormones and stress.

Some people with variegate porphyria have skin that is overly sensitive to sunlight (photosensitive). Areas of skin exposed to the sun develop severe blistering, scarring, changes in pigmentation, and increased hair growth. Exposed skin becomes fragile and is easily damaged.

Rarely, the signs and symptoms of variegate porphyria can begin in infancy or early childhood. In such cases, the signs and symptoms are usually more severe than those starting later in life. In addition to the health problems described above, children with this disorder may have mental retardation and grow more slowly than other children.

Genetics

Variegate porphyria has an autosomal dominant pattern of inheritance.

Mutations in the PPOX gene cause variegate porphyria.<ref name="pmid10343202">,

 Variegate porphyria: past, present and future, 
 Skin Pharmacol. Appl. Skin Physiol., 
 1998,
 Vol. 11(Issue: 6),
 pp. 310–20,
 DOI: 10.1159/000029854,
 PMID: 10343202,
 
 
 Full text,</ref> The PPOX gene makes a membrane bound mitochondrial enzyme called protoporphyrinogen oxidase, which is critical to the chemical process that leads to heme production. The activity of this enzyme is reduced by 50 percent in most people with variegate porphyria. In severe cases that begin early in life, the enzyme is almost completely inactive. Nongenetic factors such as certain drugs, stress, and others listed above can increase the demand for heme and the enzymes required to make heme. The combination of this increased demand and reduced activity of protoporphyrinogen oxidase disrupts heme production and allows byproducts of the process to accumulate in the liver, triggering an acute attack.

Variegate porphyria is inherited in an autosomal dominant pattern, which means the defective gene is located on an autosome, and inheriting one copy of the defective gene from an affected parent is sufficient to cause the disorder. More severe cases result from inheriting two copies of the defective gene.

The entire PPOX gene has about 8kb with 13 exon sequences. It was successfully cloned from a cDNA library in 1995 revealing that, after processing, it is 477 nucleotides long. It has previously been thought that the PPOX gene was located on human chromosome 14,<ref name="pmid3261272">,

 Linkage between the variegate porphyria (VP) and the alpha-1-antitrypsin (PI) genes on human chromosome 14, 
 Hum. Genet., 
 
 Vol. 79(Issue: 3),
 pp. 289–90,
 DOI: 10.1007/BF00366255,
 PMID: 3261272,</ref> however mapping experiments (FISH) have shown that it is near 1q23.<ref name="pmid8634714">, 
 Partial characterization and assignment of the gene for protoporphyrinogen oxidase and variegate porphyria to human chromosome 1q23, 
 Hum. Mol. Genet., 
 
 Vol. 4(Issue: 12),
 pp. 2387–90,
 DOI: 10.1093/hmg/4.12.2387,
 PMID: 8634714,
 
 
 Full text,</ref>  An additional aggravating mutation affecting  variegate porphyria can be found at 6p21.3 on the HFE gene.<ref name="pmid10401000">, 
 Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria, 
 Hum. Mol. Genet., 
 
 Vol. 8(Issue: 8),
 pp. 1517–22,
 DOI: 10.1093/hmg/8.8.1517,
 PMID: 10401000,
 
 
 Full text,</ref>

A 2006 clinical, biochemical and mutational study of eight Swiss variegate porphyria patients and their families found four novel PPOX gene mutations believed to be unique to the Swiss population.<ref name="pmid16947091">,

 Swiss patients with variegate porphyria have unique mutations, 
 Swiss Med Wkly, 
 
 Vol. 136(Issue: 31–32),
 pp. 515–9,
 
 PMID: 16947091,
 
 
 Full text,</ref>

Diagnosis

Diagnosis is by finding raised urine porphyrins, raised faecal porphyrins, markedly raised plasma porphyrins (pathognomic) and finding photosensitive cutaneous lesions on clinical examination.

Treatment

Liver transplant has been used in the treatment of this condition.<ref name="pmid15237381">,

 Recovery from a variegate porphyria by a liver transplantation, 
 Liver Transpl., 
 
 Vol. 10(Issue: 7),
 pp. 935–8,
 DOI: 10.1002/lt.20136,
 PMID: 15237381,</ref>

Epidemiology

In South Africa, the prevalence of variegate porphyria is approximately 1 in 300.<ref name=Hann2006>,

 Pediatric hematolog, 
  
 Malden, Mass.:Blackwell Pub., 
 2006, 
  
  
 ISBN 978-1-4051-3400-2,</ref> In Finland, the prevalence is approximately 1 in 75,000.<ref>, 
 Variegate porphyria. Twelve years' experience in Finland, 
 The Quarterly Journal of Medicine, 
 1980,
 Vol. 49(Issue: 194),
 pp. 191–203,
 
 PMID: 7433635,</ref>

It is also found in Argentina,<ref name="pmid18570668">,

 Genetic and biochemical studies in Argentinean patients with variegate porphyria, 
 BMC Med. Genet., 
 2008,
 Vol. 9,
 pp. 54,
 DOI: 10.1186/1471-2350-9-54,
 PMID: 18570668,
 PMC: 2467414,</ref>  Sweden,<ref name="pmid12859407">, 
 Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria, 
 Clin. Genet., 
 
 Vol. 64(Issue: 2),
 pp. 122–30,
 DOI: 10.1034/j.1399-0004.2003.00116.x,
 PMID: 12859407,</ref> and Australia.<ref>Rossi E, Chin CY, Beilby JP, Waso HF, Warnich L, 
 Variegate porphyria in Western Australian Aboriginal patients, 
 Internal Medicine Journal, 
 
 Vol. 32(Issue: 9–10),
 pp. 445–450,
 DOI: 10.1046/j.1445-5994.2002.00274.x,
 PMID: 12380696,</ref>

References

This article incorporates public domain text from The U.S. National Library of Medicine

External links

• Variegate porphyria at NIH's Office of Rare Diseases

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