Heme biosynthesis and the porphyrias

Robert J. Desnick, Manisha Balwani, Karl Anderson

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Introduction: The porphyrias are metabolic disorders each resulting from the deficiency of a specific enzyme in the heme biosynthetic pathway (Figure 30.1 and Table 30.1) [1–5]. These enzyme deficiencies are inherited as autosomal dominant X-linked, recessive, traits, with the exception of porphyria cutanea tarda (PCT), which usually is sporadic. The porphyrias are classified as either hepatic or erythropoietic depending on the primary site of overproduction and accumulation of porphyrin precursors or porphyrins (Table 30.2) although some have overlapping features. The hepatic porphyrias are characterized by overproduction and initial accumulation of porphyrin precursors and/or porphyrins primarily in the liver, whereas in the erythropoietic porphyrias, overproduction and initial accumulation of the pathway intermediates occur primarily in bone marrow erythroid cells. The major manifestations of the acute hepatic porphyrias, which typically present after puberty, are neurologic, including neuropathic abdominal pain, neuropathy, and mental disturbances. The neurologic involvement appears to be the result of hepatic production of a neurotoxic substance, as liver transplantation has prevented further occurrences in several patients who had frequent attacks of acute intermittent porphyria (AIP) [6, 7]. Steroid hormones, drugs, and nutrition influence the hepatic production of porphyrin precursors and porphyrins, thereby precipitating or increasing the severity of some hepatic porphyrias. Rare homozygous variants of the autosomal dominant hepatic porphyrias have been identified and usually manifest clinically before puberty. The symptoms in these patients are usually more severe and occur earlier than those of patients with the respective autosomal dominant porphyria (see below) [1].

Original languageEnglish (US)
Title of host publicationLiver Disease in Children, Fourth Edition
PublisherCambridge University Press
Pages509-525
Number of pages17
ISBN (Print)9781139012102, 9781107013797
DOIs
StatePublished - Jan 1 2011

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Porphyrias
Porphyrins
Heme
Hepatic Porphyria
Liver
Puberty
Nervous System
Erythropoietic Porphyria
Porphyria Cutanea Tarda
Acute Intermittent Porphyria
X-Linked Genes
Erythroid Cells
Biosynthetic Pathways
Neuralgia
Enzymes
Bone Marrow Cells
Liver Transplantation
Abdominal Pain
Steroids
Hormones

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Desnick, R. J., Balwani, M., & Anderson, K. (2011). Heme biosynthesis and the porphyrias. In Liver Disease in Children, Fourth Edition (pp. 509-525). Cambridge University Press. https://doi.org/10.1017/CBO9781139012102.031

Heme biosynthesis and the porphyrias. / Desnick, Robert J.; Balwani, Manisha; Anderson, Karl.

Liver Disease in Children, Fourth Edition. Cambridge University Press, 2011. p. 509-525.

Research output: Chapter in Book/Report/Conference proceedingChapter

Desnick, RJ, Balwani, M & Anderson, K 2011, Heme biosynthesis and the porphyrias. in Liver Disease in Children, Fourth Edition. Cambridge University Press, pp. 509-525. https://doi.org/10.1017/CBO9781139012102.031
Desnick RJ, Balwani M, Anderson K. Heme biosynthesis and the porphyrias. In Liver Disease in Children, Fourth Edition. Cambridge University Press. 2011. p. 509-525 https://doi.org/10.1017/CBO9781139012102.031
Desnick, Robert J. ; Balwani, Manisha ; Anderson, Karl. / Heme biosynthesis and the porphyrias. Liver Disease in Children, Fourth Edition. Cambridge University Press, 2011. pp. 509-525
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