Italian researchers revealed the identification of the first known case of late-onset Pompe disease, according to a new study published in the journal Scientific Reports.
The team was led by Massimo Delledonne, PhD, a professor of Genetics in the Department of Biotechnology at the University of Verona in Italy. He generated the whole exome sequence of the Italian nobleman Cangrande della Scala, who lived between 1291 and 1329.
They then performed an in-depth variant annotation, high-quality filtering, and interpretation of the data and identified a genotype associated with late-onset Pompe disease.
“This genetic diagnosis was concordant with the limited clinical history available for Cangrande della Scala, who likely represents the earliest known case of this autosomal recessive metabolic disorder,” the researchers wrote.
Read more about Pompe disease history
In the present case, the researchers identified 2 pathogenic variants in the GAA gene, which encodes the α-glucosidase enzyme and is mutated in Pompe disease.
“The clinical phenotype of this disease is consistent with data from the historical records, suggesting that Cangrande della Scala is the earliest known case of this prototypic lysosomal storage disorder,” the researchers wrote.
Cangrande della Scala is an important historic figure who has scarce private life and health data due to the Scaliger family archives being destroyed. This is an important example of how next-generation sequencing can provide information about historical figures and help clarify details about their lives in an objective and accurate manner.
Pompe disease was first described by the Dutch pathologist Johannes Cassianus Pompe in 1932. The α-glucosidase enzyme was discovered by the Belgian biochemist Henri-Gery Hers, and the Austro-Hungarian biochemist Gerty Theresa Cori demonstrated that it was missing in patients with Pompe disease. This is the first report of a case of late-onset Pompe disease that occurred more than 700 years ago.
Iadarola B, Lavezzari D, Modi A, et al. Whole-exome sequencing of the mummified remains of Cangrande della Scala (1291-1329 CE) indicates the first known case of late-onset Pompe disease. Sci Rep. 2021;26;11(1):21070. doi:10.1038/s41598-021-00559-1