The absence of acid α-glucosidase (GAA) in the hypoglossal nerve may lead to histopathological appearance and neurodegeneration according to a study in a mouse model of Pompe disease.

It is thought that the dysfunction of the hypoglossal nerve, the nerve that controls tongue movement, leads to lingual impairment and sleep-disordered breathing, 2 common symptoms of Pompe disease.

Read more about the symptoms of Pompe disease.

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However, no studies directly showed that the lack of GAA enzyme leads to the degeneration of the hypoglossal nerve. 

In the present study, a team of researchers led by David D. Fuller, PhD., a professor in the Department of Physical Therapy at the University of Florida generated a novel transgenic mouse model that lacks GAA activity in choline acetyltransferase-positive neurons. In other words, these animals did not have GAA enzyme in the hypoglossal nerves but had it in their skeletal myofibers. Their aim was to see whether the lack of GAA enzyme in the hypoglossal nerves will lead to their progressive degeneration.

The researchers counted the number of hypoglossal nerves in animals that were 1 to 3 months old and in animals that were 21 to 24 months old. They found that the young animals had an average of 658 hypoglossal nerves while the old ones had 617 hypoglossal nerves on average. This corresponds to about a 7% decline in the number of hypoglossal nerves over this age span.

Importantly, there were striking differences in the histological appearance of the hypoglossal nerves in the animals of different ages, the authors reported. They said that the hypoglossal nerves of the older animals had markedly enlarged soma and extensive vacuolization, which are “prototypical hallmarks” of lysosomal storage diseases such as Pompe disease. 

The researchers are now evaluating the hypoglossal nerves in wild-type mice of the same age. 

These preliminary results were published in the FASEB Journal.


Barral BE, Singer ML, Rana S, et al. Hypoglossal motoneuron (XII MN) survival over the lifespan in Pompe disease. FASEB J. Published online May 13, 2022. doi:10.1096/fasebj.2022.36.S1.R3681