Introduction
The Limb Girdle Muscular Dystrophies (LGMD) are a heterogeneous group of genetically inherited myopathies characterized by progressive weakness of the limb-girdle muscles. Pompe disease (PD) is a treatable lysosomal storage disorder with overlapping clinical features. The prevalence of these muscles disorders in Argentina is unknown.
Aims
To describe the frequency of LGMD and PD and the variants identified in a group of Argentinean patients.
Methods
A retrospective multicenter descriptive study was conducted in patients with muscle weakness investigated by a genetic panel for LGMD and PD through Next Generation Sequencing. The studied genes included: SGCA, SGCB, SGCG, SGCD, CAPN3, DYSF, TCAP, FKRP, ANO5, HNRPDL, GAA, CAV3.
Results
Samples from 472 patients were studied (259 males, mean age 39.0 ± 20.1 years old). In 51 patients (10.8%), a genetic disorder was confirmed. The most frequent diagnoses were: LGMD 2A/R1 (CAPN3) in 3%, Pompe Disease (GAA) in 2.5%, LGMD 2B/R2 (DYSF) in 2.1% and LGMD 2I/R9 (FKRP) in 0.8%. The main variants identified were CAPN3, c.1076C > T (p.P359L); GAA, c.-32 13 T > G; DYSF, c.5399_5400dupCC (p.F1801fs*24) and FKRP, c.826C > A (p.Leu276Ile). In only two of the 12 patients with a definitive diagnosis of PD the panel was carried out for screening purposes (0.4%).
Discussion
This panel confirmed a genetic muscular disorder in 10.8% of the investigated population. LGMD 2A/R1 was the most frequent genetic diagnosis. A definitive molecular diagnosis of Pompe disease was confirmed in 2.5% of the patients however, only 0.4% of the PD cases were new diagnosis.