Muscle MRI can be an important tool for supporting clinical diagnosis and evaluating patients with late-onset Pompe disease (LOPD) longitudinally, a new case study published in Genes revealed.

Muscle MRI is convenient, radiation-free, and has a high degree of consistency in detecting disease changes such as fat replacement and edema and can be considered a valuable biomarker not only for diagnosing and monitoring the condition but also determining the appropriate time for therapy initiation, the researchers noted.

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The authors present a case study of three siblings with LOPD who carry a combination of two variants, one of which has yet to be documented in the literature. The siblings show differences in age of onset, symptoms, levels of urinary tetrasaccharides, and muscle MRI results, highlighting the significant phenotypic variability of LOPD and the difficulty in determining the ideal time to initiate therapy, they added.

The first patient is a 7-month-old infant with a healthy older sister (patient 2) and brother (patient 3). The first patient did not have any respiratory infections, and his blood samples were standard, except for a slight increase in CPK (275 mU/mL at 5 months of age; 316 mU/mL at 6 months of age. Notably, normal CPK values range from 24 to 190 U/L. Moreover, a dry blood spot test for Pompe disease identification revealed borderline values (1.9 µmol/L/h; normal value > 2).

Patient 2, who is 8 years of age, reported no such symptoms and was admitted to the pediatric department at 7 years of age due to a urinary tract infection. She reported mild steatosis during an abdomen ultrasound.

Patient 3 underwent a Pompe disease screening at 10 years of age, which was negative. His echocardiography and neurologic assessment results were reported to be normal, while his dry blood spot showed enzyme activity on the borderline. Moreover, his GAA sequencing results revealed the same mutations found in his younger siblings.

The follow-up period for Enzyme Replacement Therapy (ERT) for patient 2 was every week. In contrast, patient 3 was evaluated every 4 to 6 months and underwent muscle MRI every 12 months, while patient 1 was assessed every 3 to 4 months.

The Pompe Disease Newborn Screening Working Group in 2017 proposed that the most effective results from ERT can be obtained when the treatment is initiated when the patient shows measurable signs of the disease but is still clinically asymptomatic as a form of preventive medicine. More studies are necessary to confirm or reject these findings.

“Muscle MRI can be considered a potential useful biomarker not only for diagnosis and follow-up but also to define when to start therapy,”the authors highlighted.

In recent years, the number of presymptomatic cases of LOPD has increased due to factors such as screening within families of diagnosed individuals, increased awareness of the disease, and the implementation of expanded newborn screening, the researchers noted.


Faraguna, MC, Crescitelli, V, et al. Treatment dilemma in children with late-onset Pompe disease. Genes. Published online January 30, 2023. doi:10.3390/genes14020362