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Porphyrins, porphyrin metabolism, porphyrias. III. Diagnosis, care and monitoring in porphyria cutanea tarda--suggestions for a handling programme.
Scand J Clin Lab Invest. 2000 Nov; 60(7):561-79.SJ

Abstract

Deficiency of the fifth enzyme in haem synthesis, uroporphyrinogen decarboxylase (UPGD), may give rise to accumulation and excretion of poly-carboxylated porphyrins, as well as to clinical manifestations in the form of a phototoxic skin reaction and liver engagement leading to cirrhosis and hepatocellular cancer. The cutaneous reaction, presenting as skin fragility and blisters on areas exposed to sun--porphyria cutanea tarda (PCT)--develops only in individuals with a remaining hepatic UPGD activity less than 20% of normal. Experimental results and clinical observation give evidence that PCT is a multifactorial disease. In some individuals a 50%, decrease in UPGD activity is a consequence of inheritance of an allele with a mutation in the gene programming for the enzyme, but in these gene carriers, as well as in the other patients with overt PCT, the activity of the hepatic enzyme is reduced below the critical level by the action of specific inhibitors. In the generation of the enzyme inhibitors, iron plays a central role by promoting the formation of reactive oxygen species, a process where a specific class of cytochrome enzymes; cytochrome P450 1A (CYP4501A), participates. The varying individual susceptibility to development of the disease can be discussed in terms of differences in a spectrum of factors that affect the availability of the free form of this element in the liver, or its pathogenic action. In the article the roles of chronic viral infection, alcohol abuse and exposition to polyhalogenated cyclic hydrocarbons are considered in the light of effects on the availability of iron in the liver. Some genetic prerequisites for susceptibility to PCT-inducing agents are included in a tentative model for the disease, i.e. mutations in the UPGD gene and in the HFE gene affected in haemochromatosis, as well as genetically steered inducibilities of the genes programming for CYP4501A and the rate-limiting enzyme in haem synthesis, 5-aminolevulinate synthase. With the pathogenic model as a basis the different therapeutic strategies that can be applied are discussed, and suggestions for a handling programme for the patient presenting with PCT put forward.

Authors+Show Affiliations

Porphyria Centre Sweden, CMMS, Huddinge University Hospital, Stockholm, Sweden. porfyri@swipnet.seNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

11202050

Citation

Thunell, S, and P Harper. "Porphyrins, Porphyrin Metabolism, Porphyrias. III. Diagnosis, Care and Monitoring in Porphyria Cutanea Tarda--suggestions for a Handling Programme." Scandinavian Journal of Clinical and Laboratory Investigation, vol. 60, no. 7, 2000, pp. 561-79.
Thunell S, Harper P. Porphyrins, porphyrin metabolism, porphyrias. III. Diagnosis, care and monitoring in porphyria cutanea tarda--suggestions for a handling programme. Scand J Clin Lab Invest. 2000;60(7):561-79.
Thunell, S., & Harper, P. (2000). Porphyrins, porphyrin metabolism, porphyrias. III. Diagnosis, care and monitoring in porphyria cutanea tarda--suggestions for a handling programme. Scandinavian Journal of Clinical and Laboratory Investigation, 60(7), 561-79.
Thunell S, Harper P. Porphyrins, Porphyrin Metabolism, Porphyrias. III. Diagnosis, Care and Monitoring in Porphyria Cutanea Tarda--suggestions for a Handling Programme. Scand J Clin Lab Invest. 2000;60(7):561-79. PubMed PMID: 11202050.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Porphyrins, porphyrin metabolism, porphyrias. III. Diagnosis, care and monitoring in porphyria cutanea tarda--suggestions for a handling programme. AU - Thunell,S, AU - Harper,P, PY - 2001/2/24/pubmed PY - 2001/3/27/medline PY - 2001/2/24/entrez SP - 561 EP - 79 JF - Scandinavian journal of clinical and laboratory investigation JO - Scand. J. Clin. Lab. Invest. VL - 60 IS - 7 N2 - Deficiency of the fifth enzyme in haem synthesis, uroporphyrinogen decarboxylase (UPGD), may give rise to accumulation and excretion of poly-carboxylated porphyrins, as well as to clinical manifestations in the form of a phototoxic skin reaction and liver engagement leading to cirrhosis and hepatocellular cancer. The cutaneous reaction, presenting as skin fragility and blisters on areas exposed to sun--porphyria cutanea tarda (PCT)--develops only in individuals with a remaining hepatic UPGD activity less than 20% of normal. Experimental results and clinical observation give evidence that PCT is a multifactorial disease. In some individuals a 50%, decrease in UPGD activity is a consequence of inheritance of an allele with a mutation in the gene programming for the enzyme, but in these gene carriers, as well as in the other patients with overt PCT, the activity of the hepatic enzyme is reduced below the critical level by the action of specific inhibitors. In the generation of the enzyme inhibitors, iron plays a central role by promoting the formation of reactive oxygen species, a process where a specific class of cytochrome enzymes; cytochrome P450 1A (CYP4501A), participates. The varying individual susceptibility to development of the disease can be discussed in terms of differences in a spectrum of factors that affect the availability of the free form of this element in the liver, or its pathogenic action. In the article the roles of chronic viral infection, alcohol abuse and exposition to polyhalogenated cyclic hydrocarbons are considered in the light of effects on the availability of iron in the liver. Some genetic prerequisites for susceptibility to PCT-inducing agents are included in a tentative model for the disease, i.e. mutations in the UPGD gene and in the HFE gene affected in haemochromatosis, as well as genetically steered inducibilities of the genes programming for CYP4501A and the rate-limiting enzyme in haem synthesis, 5-aminolevulinate synthase. With the pathogenic model as a basis the different therapeutic strategies that can be applied are discussed, and suggestions for a handling programme for the patient presenting with PCT put forward. SN - 0036-5513 UR - https://www.unboundmedicine.com/medline/citation/11202050/Porphyrins_porphyrin_metabolism_porphyrias__III__Diagnosis_care_and_monitoring_in_porphyria_cutanea_tarda__suggestions_for_a_handling_programme_ L2 - http://www.diseaseinfosearch.org/result/5879 DB - PRIME DP - Unbound Medicine ER -
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