Acute Intermittent Porphyria: Clinical Designations for Individuals Heterozygous for an HMBS Pathogenic Variant 1

Clinical DesignationUrine PBG 2-to-Creatinine RatioOccurrence of Acute Porphyria Attacks 3Comment
Active (symptomatic) AIP Not defined≥1 in the last 2 years
  • Sporadic AIP: 1-3 acute porphyria attacks in any 12-month period within the last 2 years
  • Recurrent AIP: ≥4 acute porphyria attacks in a maximum period of 12 months within the last 2 years
Symptomatic high excreter ≥4 times the ULNNone in the last 2 yearsIndividual who has chronic long-standing manifestations of acute porphyria (e.g., pain or other porphyria-related manifestations in the absence of other likely explanations)
Asymptomatic high excreter Individual who has confirmed acute porphyria but no acute porphyria-related manifestations in the last 2 years
Asymptomatic AIP (acute porphyria in remission) <4 times the ULNNone in the last 2 yearsIndividual who has had ≥1 acute porphyria attack at some time in the past
Latent (inactive) AIP None to date
  • Latent at-risk individual: An asymptomatic individual with a positive family history of AIP in whom an HMBS pathogenic variant was identified during screening of family members
  • Latent low-risk individual: An asymptomatic individual with no known family history of AIP in whom the identification of an HMBS pathogenic variant was an incidental finding 4

AIP = acute intermittent porphyria; PBG= porphobilinogen; ULN = upper limit of normal

1.

HMBS pathogenic variant known to be associated with AIP

2.

The quality of the PBG analysis should be within specifications set by Ipnet EQAS (or another EQA organization, such as RCPAQAP performance specifications) [Aarsand et al 2011].

3.

An acute porphyria attack is defined as a urine PBG-to-creatinine ratio ≥10 times the upper limit of normal in the presence of two or more porphyria manifestations typically persisting for more than 24 hours in the absence of other likely explanations.

4.

"Incidental finding" in this context refers to the identification of a pathogenic variant in a gene that does not account for the phenotype that prompted the diagnostic testing.

From: Acute Intermittent Porphyria

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