Raising Awareness of Late-onset Pompe Crucial to Fight Diagnosis Delay, Study Says

Raising Awareness of Late-onset Pompe Crucial to Fight Diagnosis Delay, Study Says
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Increased awareness of late-onset Pompe disease (LOPD) is crucial to shorten the delay in diagnosis and start appropriate treatment as early as possible, a study says.

The study, “Late-onset Pompe disease (LOPD) in Belgium: clinical characteristics and outcome measures,” was published in the Orphanet Journal of Rare Diseases.

LOPD is caused by mutations in the GAA gene. This gene provides instructions for making an enzyme known as acid alpha-glucosidase (GAA) that is responsible for the breakdown of a sugar molecule called glycogen. Without this enzyme, glycogen starts accumulating inside cells until it reaches toxic levels, impairing certain organs and systems.

Current treatment for LOPD involves providing patients with the enzyme they are missing. These enzyme replacement therapies (ERTs) should be started as soon as possible to ensure the best possible outcome.

To characterize the prevalence, presentation, and diagnosis of LOPD in Belgium, investigators conducted a retrospective study with data from 52 LOPD patients followed at seven neuromuscular reference centers in the country.

In addition, the researchers assessed the sensitivity of different outcome measures, including the activity limitations (ActivLim) score, the six-minute walk test (6MWT; a measure of exercise capacity), and the 10-meter walk test (10MWT). This analysis was based on seven-year data gathered from 2010 to 2017 from the same population of LOPD patients.

Results showed that LOPD has an estimated prevalence of 3.9 cases per million in Belgium.

The mean age at symptom onset among the 52 patients was 28.9 years. However, on average, patients only received a confirmed genetic diagnosis of the disease at nearly 41 years of age, meaning there was an approximate 12-year delay in diagnosis.

Of the patients, 75% initially presented with limb-girdle weakness (muscle weakness in the arms and legs). In 13%, respiratory symptoms were the only manifestation of LOPD. A quarter of the 32 patients who had brain imaging scans had some type of abnormality.

Nineteen patients (37%) started receiving non-invasive ventilation when they reached a mean age of 49.5 years. They remained on treatment for an average period of 15 years after  symptom onset.

Apart from one patient, all received ERT for an average period of 8.1 years. The mean age at which patients started ERT was 41.2 years.

Genetic analyses revealed that all patients were compound heterozygotes, meaning they carried different mutations on each of the two copies of the GAA gene. The c.-32-13 T > G (IVS1) mutation was present in 96% of the patients, making it the most common genetic variant found in this population.

Regarding outcome measures, the investigators found that the 6MWT, the Medical Research Council sum score of limb muscle strength, and forced vital capacity (a measure of lung function) in a seated and supine position, all decreased, or worsened, over time with disease progression.

“This deterioration was not revealed by the 10MWT and ActivLim score, although our data suggested a trend towards a decline,” they wrote. “Awareness on LOPD should even be further increased, as we found a long diagnostic delay as described in other populations. As ERT is more effective in the beginning of the disease, early start of therapy is important.”

“In the follow-up of patients, physical outcome measures and patient reported outcome measures are needed, as the relation between these two is not straightforward. The 6MWD, but not the ActivLim score, is a sensitive outcome measure to follow up LOPD patients,” they concluded.

Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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