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
evaluated muscle biopsies,

fulfilled the
inclusion criteria

activity of GAA


Baseline characteristics of patients with unclassified LGMW

Median age
51 years

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.


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