Researchers carried out a study to characterize the clinical manifestations and acid alpha-glucosidase (GAA) mutations of a group of patients with late-onset Pompe disease (LOPD), as published in Annals of Translational Medicine.

LOPD is distinguished from infantile-onset Pompe disease (IOPD) in that the symptoms are typically less severe, manifesting as progressive respiratory and proximal limb muscle weakness. In addition, LOPD is also typically characterized by GAA gene mutations and a decrease in lymphocytic GAA activity.

Zhao and colleagues decided to study 14 patients with LOPD who were seen at the First Affiliated Hospital of Nanjing Medical University in China. The researchers sought to identify the clinical manifestations of the disease and to carry out relevant genetic tests.

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The results demonstrated a heterogeneity of clinical symptoms experienced by the patients with LOPD. Eight of them presented with progressive limb weakness as an initial symptom, while 3 experienced airway infection with respiratory failure.

Among the later clinical features described by the participants were mild mitral and tricuspid insufficiency, extrapulmonary arterial hypertension, proximal limb-girdle weakness, osteoporosis, intermittent diarrhea, and fatigue. GAA activity was found in 13 patients, with a mean level of 0.20 µmol/L/h (0–0.36 µmol/L/h).

Next-generation sequencing of the GAA gene revealed 17 GAA mutations: 11 missense types and 6 deletion types. In addition, researchers discovered that c.2238G>C (p.W746C) was the most frequent variant, being at an allele frequency of 14.3%.

The researchers also discovered 4 novel variants that potentially related to the pathogenicity of LOPD: c.1299G>C (p.Q433H), c.1409A>G (p.N470S), c.2242delG (p.E748Rfs*16), and c.2832delA (p.E945Sfs*78).

“Considering the high fatality rate of IOPD, the high disability rate of LOPD, and the high medical costs associated with the disease, prenatal diagnosis and neonatal enzymology screening are recommended,” Zhao et al concluded.


Zhao HH, Ma Z, Ying ZX, et al. Clinical manifestations and acid inalpha-glucosidase mutation characterisation of a cohort of patients with late-onset Pompe disease in eastern China. Ann Transl Med. 2021;9(24):1803. doi:10.21037/atm-21-3710