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Erythropoietic and hepatic porphyrias.
J Inherit Metab Dis 2000; 23(7):641-61JI

Abstract

Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10%, of patients. Acute hepatic porphyrias (delta-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological-psychiatric and cardiovascular manifestations requiring early diagnosis to avoid life-threatening complications. Acute hepatic porphyrias are pharmacogenetic and molecular regulatory diseases (without porphyrin accumulation) mainly induced by drugs, sex hormones, fasting or alcohol. The disease process depends on the derepression of hepatic delta-aminolaevulinic acid synthase following haem depletion. In contrast to the acute porphyrias, nonacute, chronic hepatic porphyrias such as porphyria cutanea tarda are porphyrin accumulation disorders leading to cutaneous symptoms associated with liver disease, especially caused by alcohol or viral hepatitis. Alcohol, oestrogens, haemodialysis, hepatitis C and AIDS are triggering factors. Porphyria cutanea tarda is the most common porphyria, followed by acute intermittent porphyria and erythropoietic protoporphyria. The molecular genetics of the porphyrias is very heterogenous. Nearly every family has its own mutation. The mutations identified account for the corresponding enzymatic deficiencies, which may remain clinically silent throughout life. Thus, the recognition of the overt disorder with extrahepatic manifestations depends on the demonstration of biochemical abnormalities due to these primary defects and compensatory hepatic overexpression of hepatic delta-aminolaevulinic acid synthase in the acute porphyrias. Consequently, haem precursors are synthesized in excess. The increased metabolites upstream of the enzymatic defect are excreted into urine and faeces. The diagnosis is based on their evaluation. Primary enzymatic or molecular analyses are noncontributary and may be misleading. Acute polysymptomatic exacerbations accompany a high excretory constellation of porphyrin precursors delta-aminolaevulinic acid and porphobilinogen. Homozygous or compound heterozygous variants of acute hepatic porphyrias may already manifest in childhood.

Authors+Show Affiliations

Division of Clinical Biochemistry, Faculty of Medicine, Philipps University, Marburg, Germany. Ulrich.Gross@aranea.deNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

11117426

Citation

Gross, U, et al. "Erythropoietic and Hepatic Porphyrias." Journal of Inherited Metabolic Disease, vol. 23, no. 7, 2000, pp. 641-61.
Gross U, Hoffmann GF, Doss MO. Erythropoietic and hepatic porphyrias. J Inherit Metab Dis. 2000;23(7):641-61.
Gross, U., Hoffmann, G. F., & Doss, M. O. (2000). Erythropoietic and hepatic porphyrias. Journal of Inherited Metabolic Disease, 23(7), pp. 641-61.
Gross U, Hoffmann GF, Doss MO. Erythropoietic and Hepatic Porphyrias. J Inherit Metab Dis. 2000;23(7):641-61. PubMed PMID: 11117426.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erythropoietic and hepatic porphyrias. AU - Gross,U, AU - Hoffmann,G F, AU - Doss,M O, PY - 2000/12/16/pubmed PY - 2001/3/10/medline PY - 2000/12/16/entrez SP - 641 EP - 61 JF - Journal of inherited metabolic disease JO - J. Inherit. Metab. Dis. VL - 23 IS - 7 N2 - Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10%, of patients. Acute hepatic porphyrias (delta-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological-psychiatric and cardiovascular manifestations requiring early diagnosis to avoid life-threatening complications. Acute hepatic porphyrias are pharmacogenetic and molecular regulatory diseases (without porphyrin accumulation) mainly induced by drugs, sex hormones, fasting or alcohol. The disease process depends on the derepression of hepatic delta-aminolaevulinic acid synthase following haem depletion. In contrast to the acute porphyrias, nonacute, chronic hepatic porphyrias such as porphyria cutanea tarda are porphyrin accumulation disorders leading to cutaneous symptoms associated with liver disease, especially caused by alcohol or viral hepatitis. Alcohol, oestrogens, haemodialysis, hepatitis C and AIDS are triggering factors. Porphyria cutanea tarda is the most common porphyria, followed by acute intermittent porphyria and erythropoietic protoporphyria. The molecular genetics of the porphyrias is very heterogenous. Nearly every family has its own mutation. The mutations identified account for the corresponding enzymatic deficiencies, which may remain clinically silent throughout life. Thus, the recognition of the overt disorder with extrahepatic manifestations depends on the demonstration of biochemical abnormalities due to these primary defects and compensatory hepatic overexpression of hepatic delta-aminolaevulinic acid synthase in the acute porphyrias. Consequently, haem precursors are synthesized in excess. The increased metabolites upstream of the enzymatic defect are excreted into urine and faeces. The diagnosis is based on their evaluation. Primary enzymatic or molecular analyses are noncontributary and may be misleading. Acute polysymptomatic exacerbations accompany a high excretory constellation of porphyrin precursors delta-aminolaevulinic acid and porphobilinogen. Homozygous or compound heterozygous variants of acute hepatic porphyrias may already manifest in childhood. SN - 0141-8955 UR - https://www.unboundmedicine.com/medline/citation/11117426/Erythropoietic_and_hepatic_porphyrias_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0141-8955&date=2000&volume=23&issue=7&spage=641 DB - PRIME DP - Unbound Medicine ER -