Study objective and method
Examine patients with LGMW and/or hyperCKemia and undiagnosed muscle biopsy for LOPD
Inclusion criteria: Inconclusive LGMW with undiagnosed muscle biopsies
Of the
340
evaluated muscle biopsies,
69
fulfilled the
inclusion criteria
Testing:
DBS+enzyme
activity of GAA
Results
Baseline characteristics of patients with unclassified LGMW
Median age
51 years
Median
symptom onset
6 years
Clinical and laboratory data of patients with unclassified LGMW
Median DBS GAA activity: 1.18 nmol/punch×21 hours
Reduced GAA activity was identified through enzyme kinetic testing in two patients
Myopathic symptoms
Laboratory results
Diagnostic yield of LOPD: 2/69 (2.9%)
Patient 1
Patient 2
A 22-year–old Caucasian female with the chief complaint of muscular exertion intolerance associated with muscle aches and cramps.
Patient profile
A 29-year–old Caucasian male with atrophies of the shoulder, pelvic girdle, and paravertebral muscles. Predominantly left-sided scapula alata and positive Gower’s sign.
Completely unspecific myopathic changes with evidence of small lipid droplets
Muscle biopsy
• Suspicious changes associated with Pompe disease
• Vacuolated muscle fibers
• Glycogen storage with enhanced lysosomal activity
No signs of HCM, FVC: <80%
Other findings
No signs of HCM, FVC: 72%
LOPD not only demonstrates wide variability in the clinical phenotype but also in the
histopathological changes in the skeletal muscles.
Conclusion
Revisiting muscle biopsies is important in neuromuscular disease diagnosis.
Muscle biopsy can aid in LOPD identification, but glycogen-related vacuolation can be absent.
An inconclusive muscle biopsy does not rule out Pompe disease.
DBS evaluation should precede muscle biopsy for all LGMW patients
ALAT: Alanine aminotransferase; AST: Aspartate transaminase; CK: Creatine kinase; DBS: Dried blood spots; FVC: Forced vital capacity; HCM: Hypertrophic cardiomyopathy; LGMW: Limb-girdle myopathic weakness; LOPD: Late-onset Pompe disease.
Golsari A, Nasimzadah A, Thomalla G, et al. Prevalence of adult Pompe disease in patients with proximal myopathic syndrome and undiagnosed muscle biopsy. Neuromuscul Disord. 2018;28(3):257–261.
MAT-KW-2300241 V1 Jul 2023