Late-Onset Pompe Disease Presenting with Isolated Tongue Involvement

Abstract

Late-onset Pompe disease (LOPD) is a rare autosomal recessive metabolic disorder that is caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), which is responsible for glycogen breakdown. It has a wide clinical spectrum but usually presents with limb girdle and respiratory muscles weakness. Tongue involvement has been rarely reported as the sole initial symptom of LOPD. A 65-year-old male presented with difficulty in speech and eating for a 4-year duration. He started to notice speech difficulty with production of particular speech sounds such as /l/, /d/, and /t/. Within 1 year, he developed difficulties in manipulating food with the tongue and oral residue in lateral sulci requiring digital manipulation, which was suggestive of tongue muscles weakness. Clinical examination showed tongue fasciculations, mild atrophic changes, and mild tongue weakness. Investigations showed mildly elevated creatine kinase levels, and electromyography of the tongue muscles revealed moderate spontaneous activity, denervation, chronic reinnervation with high-amplitude motor unit potentials, and positive sharp waves, with preserved recruitment. Given the diagnostic uncertainty, a screening for LOPD was performed using a dried blood spot, and GAA enzyme activity levels were found to be low; 1.06 μmol/L/h (reference values in adults: 2.10-29.00 μmol/L/h). Next-generation sequencing showed pathogenic variant in GAA gene, confirming the diagnosis of LOPD. This rare report of LOPD presenting with isolated tongue involvement adds to the expanding phenotypic variability of this disease. Tongue involvement is an important and early clinical sign of LOPD that needs careful evaluation and can aid in early diagnosis of this rare and treatable disease.

Keywords: Acid maltase deficiency; Glycogen storage disease type II; Late-onset Pompe disease; Pompe disease; Tongue weakness.