research summary

Association Between Gene Mutations, Enzyme Activity in Acute Intermittent Porphyria

No significant association was observed between the mutation types or positions and hydroxymethylbilane synthase (HMBS) activity levels in patients with acute intermittent porphyria, according to the results of a recent study.

Acute intermittent porphyria (AIP), a type of hepatic porphyria, is partially caused by HMBS deficiency. This deficiency has been associated with mutations in the HMBS gene, with molecular analysis of this gene being the standard for AIP diagnosis. In an effort to further understand the relationship between HMBS gene mutations and HMBS activity among patients with AIP, researchers conducted a systematic review.

Several databases were used to identify 15 eligible studies that examined HMBS gene mutations in peripheral blood samples and HMBS activity in erythrocytes of 232 patients with AIP. All studies were published up to July 15, 2023.

Decreased erythrocyte HMBS activity (<70%) was observed in 90.5% (n = 210) of participants. A total of 96 mutations were identified, including:

  • 34.4% missense (n = 33)
  • 28.1% splice (n = 27)
  • 19.8% deletion (n = 19)
  • 8.3% nonsense (n = 8)
  • 9.4% insertion (n = 9)

Further, the residual enzyme activities for each type were expressed through the mean and 95% confidence interval:

  • Missense (51.2, 48.5 to 53.9)
  • Splice (57.5, 52.0 to 59.1)
  • Deletion (54.9, 50.7 to 59.1)
  • Nonsense (52.2, 44.4 to 60.0)
  • Insertion (53.2, 47.4 to 59.0)

“Different mutation types and mutation positions are not associated with the level of hydroxymethylbilane synthase activity,” the researchers concluded. “Erythrocyte hydroxymethylbilane synthase activity is often reduced to half of normal in patients with AIP, and the enzyme activity assay has a high diagnostic value in AIP.”


Li S, Lei J, Dong B, Ren Y, Yang J. HMBS gene mutations and hydroxymethylbilane synthase activity in acute intermittent porphyria: a systematic review. Medicine (Baltimore). 2023;102(39):e35144. doi:10.1097/MD.0000000000035144.