[Diagnosis recommendations for late-onset Pompe disease]

Area of Science:

• Neuromuscular Disorders
• Lysosomal Storage Diseases
• Genetics

Context:

• Pompe disease is a progressive, autosomal recessive myopathy caused by mutations in lysosomal acid-α-glucosidase.
• The late-onset form presents heterogeneously, often mimicking other neuromuscular conditions, complicating diagnosis.

Purpose:

• To establish consensus-based recommendations for diagnosing late-onset Pompe disease.
• To provide a standardized diagnostic pathway for clinicians.

Summary:

• Patients with progressive limb-girdle weakness, fatigue, cramps, or muscle pain require evaluation.
• Initial assessment includes CK levels, electromyography, and dynamic spirometry; muscle biopsy is used for inconclusive cases.
• Suspected cases or those with non-diagnostic biopsies should undergo screening for lysosomal acid-α-glucosidase deficiency via dried blood spot (DBS) testing, confirmed by enzyme activity assays and gene sequencing.

Impact:

• Aims to reduce diagnostic delays for late-onset Pompe disease.
• Facilitates earlier intervention and improved patient outcomes.
• Establishes a clear diagnostic algorithm for a rare and debilitating condition.