MLD's latest publication estimating the prevalence and incidence of RCDP

MLD is excited to announce its latest publication, “Genetic epidemiology approach to estimating birth incidence and current disease prevalence for rhizomelic chondrodysplasia punctata” recently published in the Orphanet Journal of Rare Diseases.

Rhizomelic chondrodysplasia punctata (RCDP) is an ultra-rare genetic pediatric disease caused by an impaired ability to synthesize plasmalogens. The extreme rarity of RCDP has lead to significant challenges for doctors and researchers to accurately estimate the size of the RCDP population in the US and worldwide. Most literature uses a prevalence value of 1 per 100,000 births, which is the result of a single publication out of France, which documented a single case of RCDP out of 105,374 births in the region between 1979 and 1986. While this approach provided an insight into the frequency of the disease, the approach was not well suited to accurately determine the number of individuals living with RCDP.

MLD partnered with a leading genetics epidemiology company, Leiden Analytics, to estimate the disease burden of RCDP in the US and Europe by developing a genetic epidemiological model based on large-scale full genome sequence data. To make the incidence model, two large public genomics databases (TopMed and gnomAD) were used to determine the frequency of mutations in any of five genes known to cause RCDP (PEX7, GNPAT, AGPS, FAR1 and PEX5). The model was refined by assessing the mutations and only including those known or predicted to be pathogenic (cause disease). While many of the mutations have previously been reported in the literature, new undocumented mutations were also identified. In the US alone, we predict that 2.4 million people are carriers for mutations that could cause RCDP, with almost half of those being in the PEX7 gene.

The carrier frequencies were then used to estimate the birth incidence of RCDP, which predicted 14-23 births per year in the US and 18-28 in Europe. This works out to 0.5-0.7 RCDP cases per 100,000 births, suggesting that the initial estimates were not that far off! These numbers however also indicate that there are likely many individuals that remain undiagnosed.

Dr. Tara Smith, VP Therapeutics at MLD and corresponding author of the paper says “It is an incredible boost to our program to have a better understanding of the true RCDP population. This work strongly supports the fact that the patients are out there and in need of proper diagnosis and treatment.”

When historical birth rates were used to estimate the total number of RCDP patients living in the US and Europe the data shows that there is likely between 500-800 patients alive, much higher than the number of patients currently known by any clinicians or patient networks.

“As we move forward, it will be critical to improve diagnosis of RCDP so these patients can be identified. MLD is working on a companion blood spot test that could be used as a newborn screening tool in the future, if treatments become available” noted Dr. Shawn Ritchie, CEO and Chief Scientific Officer at MLD and co-author on the paper.