Johannes C. Pompe, MD, hero of neuroscience: the man behind the syndrome.

Johannes Pompe is famous for describing type II glycogenosis, Pompe disease. However, Pompe's participation in the Dutch resistance during World War II has not been well described in the neurology literature. Pompe saved many Jews by hiding them as patients, saved a Jewish boy who was a neighbor, hid many young resistance fighters in his laboratory, resisted the Nazi call for all Dutch doctors to submit to their puppet physician's chamber, and hid a radio transmitter in the animal room of his laboratory. He was executed by firing squad in a German reprisal shortly before the end of the war. Pompe's patriotism and religious and humanitarian values seem to have been the basis for his actions. His heroic and tragic story should not be forgotten and should serve as an example to all during such dark times.

Consensus treatment recommendations for late-onset Pompe disease.

INTRODUCTION: Pompe disease is a rare, autosomal recessive disorder caused by deficiency of the glycogen-degrading lysosomal enzyme acid alpha-glucosidase. Late-onset Pompe disease is a multisystem condition, with a heterogeneous clinical presentation that mimics other neuromuscular disorders. METHODS: Objective is to propose consensus-based treatment and management recommendations for late-onset Pompe disease. METHODS: A systematic review of the literature by a panel of specialists with expertise in Pompe disease was undertaken. CONCLUSIONS: A multidisciplinary team should be involved to properly treat the pulmonary, neuromuscular, orthopedic, and gastrointestinal elements of late-onset Pompe disease. Presymptomatic patients with subtle objective signs of Pompe disease (and patients symptomatic at diagnosis) should begin treatment with enzyme replacement therapy (ERT) immediately; presymptomatic patients without symptoms or signs should be observed without use of ERT. After 1 year of ERT, patients' condition should be reevaluated to determine whether ERT should be continued.

Whole-exome sequencing of the mummified remains of Cangrande della Scala (1291-1329 CE) indicates the first known case of late-onset Pompe disease.

Mummified remains of relevant historical figures are nowadays an important source of information to retrace data concerning their private life and health, especially when historical archives are not available. Next-generation-sequencing was proved to be a valuable tool to unravel the characteristics of these individuals through their genetic heritage. Using the strictest criteria currently available for the validation of ancient DNA sequences, whole-genome and whole-exome sequencing were generated from the mummy remains of an Italian nobleman died almost 700 years ago, Cangrande della Scala. While its genome sequencing could not yield sufficient coverage for in depth investigation, exome sequencing could overcome the limitations of this approach to achieve significantly high coverage on coding regions, thus allowing to perform the first extensive exome analysis of a mummy genome. Similar to a standard "clinical exome analysis" conducted on modern DNA, an in-depth variant annotation, high-quality filtering and interpretation was performed, leading to the identification of a genotype associated with late-onset Pompe disease (glycogen storage disease type II). 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.

[Pompe and his disease]. / Pompe en zijn ziekte.

Johannes Cassianus Pompe (1901-1945) studied medicine in Utrecht and trained in Amsterdam as a pathologist. In 1932 he reported on his findings in a girl of 7 months, who had succumbed to extreme hypertrophy of the heart. Microscopical analysis showed accumulation of glycogen not only in the heart, but also in the liver, kidneys and skeletal muscles. Pompe's life was cut short near the end of World War II, when he was arrested and eventually executed by the occupying forces. Currently Pompe's disease has been classified as glycogen storage disease type II, caused by deficiency of the lysosomal enzyme alpha-glucosidase. If the deficiency is partial, the disease manifests later in life, as muscle weakness. Enzyme replacement therapy is now feasible.