Acute intermittent porphyria in childhood: a population-based study

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Acute intermittent porphyria (AIP) is a rare genetic disorder affecting heme synthesis.
• Clinical manifestations and diagnostic criteria for AIP in children are not well-established.
• Urinary delta-aminolaevulinic acid (U-ALA) and porphobilinogen (U-PBG) are key biomarkers for AIP.

Purpose of the Study:

• To establish age-adjusted reference intervals for U-ALA and U-PBG in healthy children.
• To analyze the frequency and clinical characteristics of AIP manifestations in childhood.
• To compare AIP presentation in children with that in adults.

Main Methods:

• Analyzed U-ALA and U-PBG concentrations in healthy children aged 3-16 years.
• Conducted a prospective population-based study of 61 DNA-verified pediatric AIP patients (<18 years).
• Utilized standardized investigations, structured diaries, and urine sample collection during suspected AIP attacks.

Main Results:

• Established age-group specific reference intervals for U-ALA and U-PBG in children.
• Identified elevated baseline U-ALA and U-PBG levels in gene carriers, with 25% exceeding the 90th percentile.
• Observed AIP attacks in 10% of pediatric AIP gene carriers, with initial attacks occurring before age 15.

Conclusions:

• Pediatric AIP symptoms can be subtle, short-lived, and may not always show significant U-ALA/U-PBG elevation.
• Clinical presentation of AIP in children may differ from adult presentations.
• Recommend DNA testing, follow-up, and preventive education for children of AIP gene carriers to prevent manifest AIP.