De-duplicating patient records from three independent data sources reveals the incidence of rare neuromuscular disorders in Germany

Abstract

Background Estimation of incidence in rare diseases is often challenging due to unspecific and incomplete coding and recording systems. Patient- and health care provider-driven data collections are held with different organizations behind firewalls to protect the privacy of patients. They tend to be fragmented, incomplete and their aggregation leads to further inaccuracies, as the duplicated records cannot easily be identified. We here report about a novel approach to evaluate the incidences of Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) in Germany. Methods We performed a retrospective epidemiological study collecting data from patients with dystrophinopathies (DMD and Becker muscular dystrophy) and SMA born between 1995 and 2018. We invited all neuromuscular centers, genetic institutes and the patient registries for DMD and SMA in Germany to participate in the data collection. A novel web-based application for data entry was developed converting patient identifying information into a hash code. Duplicate entries were reliably allocated to the distinct patient. Results We collected 5409 data entries in our web-based database representing 1955 distinct patients with dystrophinopathies and 1287 patients with SMA. 55.0% of distinct patients were found in one of the 3 data sources only, while 32.0% were found in 2, and 13.0% in all 3 data sources. The highest number of SMA patients was reported by genetic testing laboratories, while for DMD the highest number was reported by the clinical specialist centers. After the removal of duplicate records, the highest yearly incidence for DMD was calculated as 2.57:10,000 in 2001 and the highest incidence for SMA as 1.36:10,000 in 2014. Conclusion With our novel approach (compliant with data protection regulations), we were able to identify unique patient records and estimate the incidence of DMD and SMA in Germany combining and de-duplicating data from patient registries, genetic institutes, and clinical care centers. Although we combined three different data sources, an unknown number of patients might not have been reported by any of these sources. Therefore, our results reflect the minimal incidence of these diseases. Electronic supplementary material The online version of this article (10.1186/s13023-019-1125-2) contains supplementary material, which is available to authorized users.

Infants Diagnosed with Spinal Muscular Atrophy and 4 SMN2 Copies through Newborn Screening – Opportunity or Burden?1

“…If this is the case, the incidence rates following NBS should be much higher than the incidence, which is known in the general population. The incidence in our cohort was 1 : 7350 which is nearly identical with the figure of 1 : 7353 which was found in symptomatic patients in Germany in 2014 [48]. This is a strong argument that the majority of patients with a homozygous SMN1 deletion detected in the NBS will become symptomatic regardless of their SMN2 copy number.…”

Advances in Treatment of Spinal Muscular Atrophy – New Phenotypes, New Challenges, New Implications for Care

“…SMA is one of the most frequent monogenic neurodegenerative diseases with an incidence estimated to be around 1 : 6,000 to 1 : 10,000 in newborns [6][7][8][9]. SMA encompasses a wide clinical continuum of disease severity and has been classified into subtypes according to age at onset and the motor milestones achieved [10].…”

Newborn screening for spinal muscular atrophy in Germany: clinical results after 2 years

“…The incidence rate in newborns is usually 1:6.000 to 1:11.000 [ 2 ]. Pooled data from neuromuscular centers, genetic institutes and patient registries revealed an incidence of 1:7352 in Germany in 2014 [ 5 ].…”