Acute hepatic porphyrias: Current diagnosis & management

Research output: Contribution to journalReview article

Abstract

Each of the four acute hepatic porphyrias is due to mutation of an enzyme in the heme biosynthetic pathway. The accumulation of pathway intermediates that occur most notably when these diseases are active is the basis for screening and establishing a biochemical diagnosis of these rare disorders. Measurement of enzyme activities and especially DNA testing also are important for diagnosis. Suspicion of the diagnosis and specific testing, particularly measurement of urinary porphobilinogen, are often delayed because the symptoms are nonspecific, even when severe. Urinary porphyrins are also measured, but their elevation is much less specific. If porphobilinogen is elevated, second line testing will establish the type of acute porphyria. DNA testing identifies the familial mutation and enables screening of family members. Management includes removal of triggering factors whenever possible. Intravenous hemin is the most effective treatment for acute attacks. Carbohydrate loading is sometimes used for mild attacks. Cyclic attacks, if frequent, can be prevented by a GnRH analogue. Frequent noncyclic attacks are sometime preventable by scheduled (e.g. weekly) hemin infusions. Long term complications may include chronic pain, renal impairment and liver cancer. Other treatments, including RNA interference, are under development.

Original languageEnglish (US)
JournalMolecular Genetics and Metabolism
DOIs
StatePublished - Jan 1 2019

Fingerprint

Porphobilinogen
Hemin
Testing
Acute Intermittent Porphyria
Screening
Mutation
Kidney Neoplasms
DNA
Biosynthetic Pathways
Porphyrins
Enzymes
Liver Neoplasms
RNA Interference
Heme
Gonadotropin-Releasing Hormone
Chronic Pain
Enzyme activity
Liver
Carbohydrates
RNA

Keywords

  • GnRH analogues
  • Hemin
  • Porphobilinogen
  • Porphyrias
  • Porphyrins
  • RNA interference

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Acute hepatic porphyrias : Current diagnosis & management. / Anderson, Karl.

In: Molecular Genetics and Metabolism, 01.01.2019.

Research output: Contribution to journalReview article

@article{fa9f7de0620e402aaf4e2e0607f477a8,
title = "Acute hepatic porphyrias: Current diagnosis & management",
abstract = "Each of the four acute hepatic porphyrias is due to mutation of an enzyme in the heme biosynthetic pathway. The accumulation of pathway intermediates that occur most notably when these diseases are active is the basis for screening and establishing a biochemical diagnosis of these rare disorders. Measurement of enzyme activities and especially DNA testing also are important for diagnosis. Suspicion of the diagnosis and specific testing, particularly measurement of urinary porphobilinogen, are often delayed because the symptoms are nonspecific, even when severe. Urinary porphyrins are also measured, but their elevation is much less specific. If porphobilinogen is elevated, second line testing will establish the type of acute porphyria. DNA testing identifies the familial mutation and enables screening of family members. Management includes removal of triggering factors whenever possible. Intravenous hemin is the most effective treatment for acute attacks. Carbohydrate loading is sometimes used for mild attacks. Cyclic attacks, if frequent, can be prevented by a GnRH analogue. Frequent noncyclic attacks are sometime preventable by scheduled (e.g. weekly) hemin infusions. Long term complications may include chronic pain, renal impairment and liver cancer. Other treatments, including RNA interference, are under development.",
keywords = "GnRH analogues, Hemin, Porphobilinogen, Porphyrias, Porphyrins, RNA interference",
author = "Karl Anderson",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.ymgme.2019.07.002",
language = "English (US)",
journal = "Molecular Genetics and Metabolism",
issn = "1096-7192",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Acute hepatic porphyrias

T2 - Current diagnosis & management

AU - Anderson, Karl

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Each of the four acute hepatic porphyrias is due to mutation of an enzyme in the heme biosynthetic pathway. The accumulation of pathway intermediates that occur most notably when these diseases are active is the basis for screening and establishing a biochemical diagnosis of these rare disorders. Measurement of enzyme activities and especially DNA testing also are important for diagnosis. Suspicion of the diagnosis and specific testing, particularly measurement of urinary porphobilinogen, are often delayed because the symptoms are nonspecific, even when severe. Urinary porphyrins are also measured, but their elevation is much less specific. If porphobilinogen is elevated, second line testing will establish the type of acute porphyria. DNA testing identifies the familial mutation and enables screening of family members. Management includes removal of triggering factors whenever possible. Intravenous hemin is the most effective treatment for acute attacks. Carbohydrate loading is sometimes used for mild attacks. Cyclic attacks, if frequent, can be prevented by a GnRH analogue. Frequent noncyclic attacks are sometime preventable by scheduled (e.g. weekly) hemin infusions. Long term complications may include chronic pain, renal impairment and liver cancer. Other treatments, including RNA interference, are under development.

AB - Each of the four acute hepatic porphyrias is due to mutation of an enzyme in the heme biosynthetic pathway. The accumulation of pathway intermediates that occur most notably when these diseases are active is the basis for screening and establishing a biochemical diagnosis of these rare disorders. Measurement of enzyme activities and especially DNA testing also are important for diagnosis. Suspicion of the diagnosis and specific testing, particularly measurement of urinary porphobilinogen, are often delayed because the symptoms are nonspecific, even when severe. Urinary porphyrins are also measured, but their elevation is much less specific. If porphobilinogen is elevated, second line testing will establish the type of acute porphyria. DNA testing identifies the familial mutation and enables screening of family members. Management includes removal of triggering factors whenever possible. Intravenous hemin is the most effective treatment for acute attacks. Carbohydrate loading is sometimes used for mild attacks. Cyclic attacks, if frequent, can be prevented by a GnRH analogue. Frequent noncyclic attacks are sometime preventable by scheduled (e.g. weekly) hemin infusions. Long term complications may include chronic pain, renal impairment and liver cancer. Other treatments, including RNA interference, are under development.

KW - GnRH analogues

KW - Hemin

KW - Porphobilinogen

KW - Porphyrias

KW - Porphyrins

KW - RNA interference

UR - http://www.scopus.com/inward/record.url?scp=85068877362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068877362&partnerID=8YFLogxK

U2 - 10.1016/j.ymgme.2019.07.002

DO - 10.1016/j.ymgme.2019.07.002

M3 - Review article

AN - SCOPUS:85068877362

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

ER -