‘Urgent’ Need in China to Better Diagnose AIP, Study Says

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A large proportion of people with acute intermittent porphyria (AIP) may still be undiagnosed in China, according to a recent study — and without a proper diagnosis, they’re not receiving needed treatment, researchers say.

“More nationwide epidemiological surveys and study of the prevalence rate of AIP patients in China are urgently required,” the scientists wrote, adding that undiagnosed patients “are at risk of developing acute attacks.”

The study, “Acute intermittent porphyria: prevalence of pathogenic HMBS variants in China, and epidemiological survey in Hebei Province, China,” was published in the journal Annals of Translational Medicine.

AIP, the most common type of acute porphyria, is caused by mutations in the HMBS gene. This gene contains instructions for making the enzyme hydroxymethylbilane synthase, which is required for heme production. Heme is a molecule that is needed for oxygen transport throughout the body.

The lack of this enzyme causes porphyrins to accumulate inside cells, including in nerve cells, and can lead to acute attacks. Symptoms of such attacks can include pain, urinary and gastrointestinal issues, and altered mental status.

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The prevalence of disease-causing mutations in the HMBS gene has been reported mostly for people living in Europe and America. Few studies have assessed its prevalence in the general Chinese population. To date, more than 500 different genetic variants have been described.

Now, researchers in China calculated the potential prevalence of five of these variants in the Chinese population.

“The number of people with pathogenic [disease-causing] HMBS variants may exceed 790,000 in China, a country with 1.4 billion population,” the researchers wrote.

Investigating the prevalence of AIP in China

For their study, the team used the China Metabolic Analysis Project (ChinaMAP) database to assess the prevalence of likely disease-causing mutations in the HMBS gene, according to guidelines established by the American College of Medical Genetics and Genomics (ACMG).

The ChinaMAP database includes whole genome sequencing (WGS) and metabolic data from people of different ethnic groups and across diverse regions in China. WGS is a technique that allows researchers to assess the entire human genome, or all genes in the human body.

The researchers compared their findings to the prevalence of disease-causing HMBS gene mutations estimated using the Genome Aggregation Database (gnomAD) genome V3.0 database. That database includes genomic data from East Asian, Ashkenazi Jewish, mixed American, African/African American, Amish, Finnish, non-Finnish European, South Asian (SAS), and other populations.

The analysis identified a total of 501 HMBS gene variants in the ChinaMAP database, of which five were deemed to be disease-causing or likely disease-causing. This resulted in an estimated overall prevalence of one disease-causing variant per 1,765 in the Chinese population. The variants, also identified outside China, varied among different racial groups.

Since AIP is a rare disease, researchers conducted an epidemiological analysis of cases reported in Hebei province from 2011 to 2020. This province lies in the north of China and has a population of more than 70 million people.

During this period, the annual incidence of AIP was estimated to range from 0.03 to 0.08 cases per million inhabitants. While generally low until 2017, it increased in 2018 and remained stable thereafter.

Over the course of that decade, 36 women and three men, with an average age of 25.59, were newly diagnosed with AIP in the province. According to researchers, that’s less than 10% of the estimated AIP patients in Hebei.

“Approximately 400 symptomatic AIP patients are estimated to exist in Hebei, whereas only 39 AIP patients have been diagnosed over 10 years, indicating a large proportion of AIP patients remain unidentified,” the researchers wrote.

While “China has made great strides in the management of rare diseases including AIP,” these findings suggest that a large proportion of patients do not have a proper porphyria diagnosis, the team noted.

“More nationwide epidemiological surveys and studies related to the penetrance rate of AIP patients in China should be performed,” they concluded.