Acute intermittent porphyria: prevalence of pathogenic HMBS variants in China, and epidemiological survey in Hebei Province, China

BACKGROUND: Acute intermittent porphyria (AIP) is a rare inherited disorder with extremely low prevalence. Early detection of patients with potential pathogenic hydroxymethylbilane synthase (HMBS) variants is crucial for clinical prognosis. This study was designed to investigate the prevalence of pathogenic HMBS variants in Chinese population. METHODS: The China Metabolic Analysis Project (ChinaMAP) database was employed to predict the prevalence of pathogenic HMBS variants in the Chinese population according to the variant interpretation guidelines of The American College of Medical Genetics and Genomics (ACMG). And the prevalence of pathogenic HMBS variants in Mixed American (AMR), African/African American (AFR), and Non-Finnish European (NFE) populations were estimated based on the Genome Aggregation Database (gnomAD) genome V3.0 database according to the guidelines of ACMG. An epidemiological investigation of AIP was conducted in Hebei Province, China through collecting the annual newly-diagnosed AIP cases of inpatients in 32 comprehensive grade III A hospitals from January 2011 to December 2020 in Hebei, China. RESULTS: A total of 5 pathogenic/likely pathogenic (P/LP) HMBS variants were identified and the prevalence of pathogenic HMBS variants was predicted to be 1/1,765. Furthermore, based on the gnomAD genome V3.0 database, the estimated prevalence of pathogenic HMBS variants was 1/1,367, 1/1,403, and 1/621 in AMR, AFR, and NFE populations, respectively. The distribution of these variants varied among different racial populations. Moreover, AIP patients were predominantly hospitalized in comprehensive grade III A tertiary hospitals in Hebei province over a 10-year period. A total of 39 patients were newly-diagnosed with AIP, and a majority of them were female (n=36). The annual incidence between 2011 and 2017 {0.03 [95% confidence interval (CI): 0.01 to 0.11] to 0.05 (95% CI: 0.07 to 0.14) per million population} was generally lower than [0.07 (95% CI: 0.03 to 0.17) to 0.08 (95% CI: 0.03 to 0.18) per million] in 2018 and thereafter. CONCLUSIONS: China has made great strides in the management of AIP. More nationwide epidemiological surveys and study of the prevalence rate of AIP patients in China are urgently required.