FRD-2022-0009 – Spanish – Plain language summary: How the Pompe Registry is helping to identify and explain gene changes in Pompe disease
What is this summary about?
This is a summary of an article originally published in the journal Human Mutation. Pompe disease is a rare genetic disorder. In the USA, one person in every 10,000 to 28,000 people is born with Pompe disease. Pompe disease develops when both parents pass on a copy of a gene, called GAA, that has a disease-causing change to it. The GAA gene contains the instructions to make an enzyme called acid alpha glucosidase; abbreviated as ‘GAA’, which breaks down glycogen into glucose. When the GAA gene contains a disease-causing change, this can lead to a total absence of GAA or the enzyme failing to function properly. As a result, glycogen builds up in cells and causes damage to organs such as the heart and muscles. There is a wide range of severity and symptoms in Pompe disease, including muscle weakness, heart and breathing issues, and extreme tiredness (fatigue). There are many changes in the GAA gene (called variants) that can result in Pompe disease. The severity of symptoms and when symptoms start partly depend on the variants that the people with Pompe disease have inherited from their parents.
What was learned & how?
Researchers looked at GAA gene variants from people with Pompe disease using a database called the Pompe Registry. Since 2004, the Pompe Registry has collected worldwide clinical information on people with Pompe disease and their gene changes. The researchers investigated how many different GAA variants are currently listed in this registry, and how common each variant was overall and in different geographical regions. The researchers assigned the people to three groups based on the age of when their symptoms began and if they had an enlarged heart diagnosed in their first year of life. Out of 1753 people enrolled in the Pompe Registry, the researchers analyzed data from 1079 people from 26 countries. 2075 GAA gene variants were identified, 80 of which had not been reported before. A harmful variant called c.-32-13T>G was the most common overall and was present in North America, Latin America and Europe.
What are the practical implications?
This analysis supports healthcare professionals and people with Pompe disease to appreciate the geographic distribution and to assess the nature of GAA variants. The findings can help with the diagnosis of Pompe disease and the understanding of how different variants relate to the start and severity of symptoms. This information will also help genetic counsellors and doctors to have discussions with people with Pompe disease and their families and caregivers about genetic risk and family planning.