Diagnosis and treatment of late-onset Pompe disease in the Middle East and North Africa region: consensus recommendations from an expert group

Abstract

Background: Pompe disease is a rare autosomal recessive disorder caused by a deficiency of the lysosomal enzyme alpha-glucosidase responsible for degrading glycogen. Late-onset Pompe disease has a complex multisystem phenotype characterized by a range of symptoms.

Methods: An expert panel from the Middle East and North Africa (MENA) region met to create consensus-based guidelines for the diagnosis and treatment of late-onset Pompe disease for the MENA region, where the relative prevalence of Pompe disease is thought to be high but there is a lack of awareness and diagnostic facilities.

Results: These guidelines set out practical recommendations and include algorithms for the diagnosis and treatment of late-onset Pompe disease. They detail the ideal diagnostic workup, indicate the patients in whom enzyme replacement therapy should be initiated, and provide guidance on appropriate patient monitoring.

Conclusions: These guidelines will serve to increase awareness of the condition, optimize patient diagnosis and treatment, reduce disease burden, and improve patient outcomes.

Fig. 1

Pathophysiology of late-onset Pompe disease. Abbreviations: GAA, acid alpha-glucosidase

Fig. 2

Biopsy from right vastus lateralis of a 46-year-old woman with LOPD. She had a long history of muscle weakness presenting with respiratory insufficiency. a Prominent fiber size variation and excess internalized nuclei with variable-sized subsarcolemmal and cytoplasmic vacuoles (H&E stain x200). b Pronounced vacuolation of many fibers, some vacuoles are slightly red-rimmed (modified Gomori trichrome stain x200). c Pronounced glycogen accumulation as intense staining of subsarcolemmal and cytoplasmic vacuoles (PAS stain x200). d Immunolabeling of multiple membrane-bound cytoplasmic vacuoles with dystrophin (Dystrophin 1, Biogenex Co. x200). Images provided by Dr Yalda Nilipour

Fig. 3

Muscle biopsy from left brachioradialis of a 40-year-old man with LOPD. He had had progressive limb–girdle muscle weakness since adulthood. a Slight variation in fiber size and some internalized nuclei with tiny cytoplasmic vacuoles in few fibers (H&E x400). b Only a little accumulation of glycogen in few fibers as punctate staining (PAS x400). c Tiny cytoplasmic vacuoles in few fibers. (Gomori trichrome x400). d Immunolabeling of dystrophin. Dot-like labelling of tiny membrane-bound cytoplasmic vacuoles in some fibers (Dystrophin 1, Biogenex Co. x400). Images provided by Dr Yalda Nilipour

Fig. 4

Algorithm for the diagnosis of LOPD. Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; CK, creatine kinase; DBS, dried blood spot; EMG, electromyography; FVC, forced vital capacity; GAA, acid alpha-glucosidase. *Alternative diagnosis made. Adapted with permission from AANEM. Diagnostic Criteria for Late-Onset (Childhood and Adult) Pompe Disease. Muscle Nerve. 2009;40:149–160 [107] © 2009 Wiley Periodicals, Inc

Fig. 5

Algorithm for treatment of LOPD. Abbreviations: ERT, enzyme replacement therapy; MRI, magnetic resonance imaging. *Restarting of ERT with alglucosidase alfa should be considered if there is rapid deterioration post-discontinuation