- Author: Maureen B Poh-Fitzpatrick, MD; Chief Editor: Dirk M Elston, MD more...
Variegate porphyria (VP) is an inherited disorder of porphyrin-heme metabolism arising from mutations of the gene encoding the enzyme protoporphyrinogen oxidase.[1, 2, 3, 4] Manifestations of variegate porphyria in any given individual may include cutaneous photosensitivity, systemic symptoms arising from neurologic dysfunction, or both.[3, 5, 6, 7, 8]
Inherited as an autosomal dominant trait, variegate porphyria is biochemically characterized by accumulations of the photosensitizing porphyrins protoporphyrin and coproporphyrin. In addition, abnormally high levels of the porphyrin precursors porphobilinogen and aminolevulinic acid are found during episodic attacks of systemic symptoms.[5, 9] Acute attack symptoms are caused by dysfunctions of central, autonomic, and peripheral nervous systems that appear to be effects of deranged heme synthesis on neurons.
A registry has been established to develop information about the prevalence of porphyrias in the United States (American Porphyria Foundation;http://www.rarediseasesnetwork.org/cms/porphyrias/registry). Unknown numbers of cases may be unrecognized or misdiagnosed as another porphyria.
Prevalence is estimated at 1 case in 300 persons in South Africa, where a protoporphyrinogen oxidase gene "founder" mutation traceable to Dutch immigrants who married there in 1680 has been widely disseminated.[11, 12] It is the most common acute porphyria in Chile, where another founder mutation was identified in 4 apparently unrelated families. Among the combined populations of 11 European countries, 70 new cases of variegate porphyria were identified over a recent 3-year period; assuming mean disease duration of 40 years, prevalence was calculated at 3.2 cases per million persons.
No well-established racial predilection is known, although the disease is common among South Africans of Dutch ancestry, many of whom inherit the founder gene propagated in that population. Most multiple case reports involve European populations or North or South American populations that include individuals with European heritage.
Variegate porphyria occurs in both men and women, but is manifested more often in women.
Variegate porphyria usually presents after puberty. Very rare childhood cases have been ascribed to the presence of 2 mutant protoporphyrinogen oxidase genes in the same individual.[16, 17]
Mild attacks of variegate porphyria may resolve within a few to several days with conservative management. Those that progress to vomiting or early signs of neuropathy usually respond to the administration of a heme analogue for 4 days. Profound attacks that are either unrecognized or inadequately treated early enough in the course may progress to long-term debility or death.
Cutaneous photosensitivity may cause difficulty performing manual labor and may limit many daily activities. Neurovisceral disorders vary from relatively mild symptoms that can remit spontaneously to profound crises that can be fatal or incapacitating for months to years.[3, 5, 6, 7, 18]
Acute attacks of variegate porphyria can be life-threatening. However, with early diagnosis of active disease, identification of asymptomatic protoporphyrinogen oxidase gene mutation carriers, and avoidance of drugs and other factors known to induce or worsen clinical expression, symptomatology among those at risk can be minimized. Good medical management of overt episodes can reduce morbidity and mortality such that the long-term outlook for patients is positive.
Patients need careful instruction about the nature of the disease and its genetic implications for their family members. Current lists of safe and unsafe drugs should be provided to patients and their physicians. Dietary instructions for maintaining adequate carbohydrate intake and for consuming a rapidly absorbed form of glucose at the first signs of an attack should be given. Effective sun avoidance practices should be advised for those patients with cutaneous photosensitivity.
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