Prevalence Of LOPD In Patients With Undifferentiated Proximal Myopathy And Undiagnosed Muscle Biopsy

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

Abbreviations

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.

Reference

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.

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MAT-KW-2300241 V1 Jul 2023