Acute intermittent porphyria

Last reviewed: June 2018

Last updated: January 2017

Summary

A rare autosomal dominant inherited disorder characterized by a partial deficiency of porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthetic pathway. As a result, porphyrin precursors, porphobilinogen (PBG), and delta-aminolevulinic acid (ALA) accumulate in the body.

Most patients remain asymptomatic, but symptoms can be triggered by use of certain drugs or alteration of nutritional status.

The most common presenting features include pain in the abdomen, extremities, back, and chest, tachycardia, hypertension, nausea, vomiting, constipation, and peripheral motor neuropathy.

The pain is neuropathic and not accompanied by inflammation.

Red or brownish urine results from marked increases in urinary excretion of heme pathway intermediates. Porphyrins are reddish and fluoresce when exposed to long-wave ultraviolet light. PBG is colorless but degrades on standing to form brownish pigments.

Definition

Acute intermittent porphyria (AIP) is a rare genetic disorder characterized by a partial deficiency of porphobilinogen deaminase (PBGD), also known as hydroxymethylbilane synthase, the third enzyme in the heme biosynthetic pathway. As a result, the porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) accumulate in the body. Urinary excretion of ALA, PBG, and porphyrins is increased. Most patients remain asymptomatic with little or no elevation in ALA, PBG, and porphyrins, but the condition can be activated after puberty by some drugs and corticosteroid hormones or by reducing dietary intake.

History and exam

Key diagnostic factors

abdominal pain
tachycardia
hypertension
dark or red urine

Full details

Other diagnostic factors

nausea
vomiting
abdominal distension
constipation
urinary hesitancy and dysuria
pain in extremities, back, and chest
proximal muscle weakness
painful hyperesthesia
mental symptoms
seizures
diarrhea
quadriparesis
respiratory failure

Full details

Risk factors

family history
female gender
drugs
elevated progesterone levels
decreased caloric or carbohydrate intake
smoking
age >13 years
alcohol

Full details

Diagnostic investigations

1st investigations to order

urinary porphobilinogen (PBG)
quantitative measure of urinary porphobilinogen (PBG)
urinary total porphyrins
serum porphobilinogen (PBG)

Full details

Investigations to consider

delta-aminolevulinic acid (ALA)
plasma total porphyrins
urinary porphyrins using high-performance liquid chromatography (HPLC)
fecal total porphyrins
fecal porphyrins using high-performance liquid chromatography (HPLC)
erythrocyte porphobilinogen deaminase (PBGD) activity
porphobilinogen deaminase (PBGD) gene sequencing
serum sodium levels
MRI brain

Full details

Treatment algorithm

ACUTE

Contributors

Authors VIEW ALL 

Gagan Sood, MD

Associate Professor

Department of Medicine and Surgery

Baylor College of Medicine

Houston

Disclosures

GS is an author of a number of references cited in this monograph.

Karl E. Anderson, MD

Professor

Departments of Preventive Medicine and Community Health and Internal Medicine

University of Texas Medical Branch

Galveston

Disclosures

KEA has received grants from the National Institutes of Health, the US Food and Drug Administration, and Alnylam Pharmaceuticals; he is an author of a number of references cited in this monograph.

Peer reviewers VIEW ALL 

Alexios Carayannopoulos, MD

Medical Director

Spine Center

Interventional Spine Physiatrist

Pain Medicine Specialist

Burlington

Disclosures

AC declares that he has no competing interests.

Kenneth E.L. McColl, MD, FRCP

Professor of Medical Sciences

Gardiner Institute

Western Infirmary

Glasgow

Disclosures

KELM declares that he has no competing interests.

Neville Pimstone, MD

Professor Emeritus of Medicine

Division of Gastroenterology

UC Davis Medical Group GI Unit

Sacramento

Disclosures

NP declares that he has no competing interests.

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Acute intermittent porphyria

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

mild acute attack

severe acute attack

recurrent noncyclic attacks

women with frequent recurrent cyclic attacks

nonresponsive to medical therapy

Contributors

Authors VIEW ALL 

Gagan Sood, MD

Disclosures

Karl E. Anderson, MD

Disclosures

Peer reviewers VIEW ALL 

Alexios Carayannopoulos, MD

Disclosures

Kenneth E.L. McColl, MD, FRCP

Disclosures

Neville Pimstone, MD

Disclosures

Differentials

Guidelines

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