Researchers found the prevalence of late-onset Pompe disease (LOPD) in a cohort of patients from neuromuscular clinics to be around 1%, with an equivalent 1% prevalence of pseudodeficiency alleles, and the prevalence of genetic carriers for Pompe disease to be 1.9%. The findings of the multicenter study were published in Neurology Genetics.
Among the 9 individuals in this study with confirmed LOPD, 8 were Caucasian (89%) and 1 was African American. Genetic testing revealed 2 pathogenic variations—the common leaky (IVS1) splice site mutation (c-32-13 T>G) and a second mutation confirmed to be pathogenic.
Nine individuals were compound heterozygous for the pseudodeficiency haplotype (c.1726G>A and c.2065G>A). Nine of 17 patients carried the common IVS1 splice site mutation, while the remaining carriers demonstrated a variety of point mutations or deletions.
“Based on . . . [newborn screening], the incidence of Pompe is much higher than what was previously established,” the study authors wrote. “This poses a major public health issue because 75% of babies found to have [acid alpha-glucosidase (GAA)] deficiency have the late-onset variant and will need surveillance to pick up early signs of disease development.”
Read more about Pompe disease differential diagnosis
Investigators obtained consent from 921 patients undergoing an evaluation for muscle disease at 13 neuromuscular clinics in the United States and Canada between July 2015 and July 2018. Overall, 31% of patients had hyperCKemia, 25.8% demonstrated proximal muscle weakness only, and 2.2% exhibited neck weakness only.
The researchers collected blood samples for an enzyme assay to detect GAA enzyme deficiency levels. They successfully obtained GAA enzyme assay results from 906 of the 921 patients.
The investigators sent out the blood samples which had GAA enzyme levels ≤ 10 pmoL/punch/h for molecular testing to ascertain GAA gene mutations and to confirm the diagnosis. While the typical limit for GAA deficiency is <3.88 pmoL/punch/h, the investigators used the conservative upper limit of 10 pmoL/punch/h to allow for the detection of carriers and patients with pseudodeficiencies.
One limitation of this study involved the participation solely of patients who actively sought out medical care, limiting the cohort to only these patients and not including individuals exhibiting mild or early signs of the disease who did not seek out specialist care.
Wencel M, Shaibani A, Goyal NA, et al. Investigating late-onset Pompe prevalence in neuromuscular medicine academic practices: the IPaNeMA study. Neurology Genetics. 2021;7(6). doi:10.1212/NXG.0000000000000623