In recent years, there has been a significant increase in the diagnosis of asymptomatic Late-Onset Pompe Disease (LOPD) patients, who are detected via family screening or Newborn Screening (NBS). The dilemma is when to start Enzyme Replacement Therapy (ERT) in patients without any clinical sign of the disease, considering its important benefits in terms of loss of muscle but also its very high cost, risk of side effects, and long-term immunogenicity. Muscle Magnetic Resonance Imaging (MRI) is accessible, radiation-free, and reproducible; therefore, it is an important instrument for the diagnosis and follow-up of patients with LOPD, especially in asymptomatic cases. European guidelines suggest monitoring in asymptomatic LOPD cases with minimal MRI findings, although other guidelines consider starting ERT in apparently asymptomatic cases with initial muscle involvement (e.g., paraspinal muscles). We describe three siblings affected by LOPD who present compound heterozygosis and wide phenotypic variability. The three cases differ in age at presentation, symptoms, urinary tetrasaccharide levels, and MRI findings, confirming the significant phenotypic variability of LOPD and the difficulty in deciding when to start therapy.
Keywords: Enzyme Replacement Therapy; Pompe disease; glycogen storage disease type 2; late onset; muscle MRI.