Nerve Damage-induced Muscle Atrophy Coexists with Pompe Disease, Study Asserts

Patients with Pompe disease also may exhibit motor neuronopathy (motor and nerve deficits due to neuron degeneration) in addition to the classical myopathy (muscle disease) features, a case study suggests.

Researchers suggest that future studies also should focus on therapies that target the central nervous system, and that clinical trial setup and patient care take into account these atypical symptoms.

The study, “Clinical features of Pompe disease with motor neuronopathy” was published in Neuromuscular Disorders.

Pompe disease is a rare genetic disorder caused by the absence or deficiency of the acid alpha-glucosidase (GAA) enzyme. When GAA activity is low, a sugar molecule called glycogen accumulates inside cells, damaging organs and tissues throughout the body, but primarily skeletal muscle, smooth muscle, and cardiac muscle.

If left untreated, the accumulation of glycogen in cardiac and skeletal muscle leads to severe and progressive muscular weakness, a typical feature of myopathy, risking heart and respiratory failure.

Previous animal and patient studies have demonstrated accumulation of glycogen in spinal motor neurons, which are involved in muscle control.

“However, there is still no clinical or electrophysiological [communication between neurons] studies focusing on the features of motor neuronopathy in patients with Pompe disease,” the authors wrote.

The team of researchers analyzed seven Pompe disease patients (six boys and one girl, 7–11 years old) who exhibited some clinical, electrophysiological, and muscular features of motor neuronopathy (selective neurodegeneration within the peripheral nervous system). All study subjects had received enzyme replacement therapy (ERT) since birth or infancy.

All patients had slurred or slow speech caused by muscle weakness (dysarthria). All patients also had weakness of the neck and in the arms and legs. Around 71% (five of seven) patients developed bilateral foot drop, meaning they had trouble lifting the front part of their feet.

Four (57%) patients had distal predominant weakness of four limbs. Distal refers to a part of the body that is farther away from the center of the body than another part, for instance, the lower leg is distal to the thigh.

Patients also had below-normal or absent reflexes, a typical feature of motor neuropathy, with preserved sensory function.

Nerve cell communication studies’ results were consistent with compromised nerve cell connectivity, and, likewise, decreased muscle function.

Besides typical muscle biopsy findings for Pompe disease, researchers also reported the existence of angular fibers, and other changes such as fiber type grouping indicative of nerve damage-induced muscle atrophy.

“Taken together, these features support the co-existence of motor neuronopathy additionally to myopathy,” the researchers stated.

“In the post-ERT era of Pompe disease, patients may present as variable atypical clinical manifestations. Carefully identifying these
presentations, including motor neuronopathy, with regular follow-up will be helpful for optimization of clinical care and setup of future clinical trials in Pompe disease,” they added.