History

A male patient in his 60s had a prior history of coronary artery disease, hypertension and hyperlipidemia; the patient also had a coronary artery bypass graft.

The patient first reported symptoms of his progressive dysphagia and dysarthria in 2019. He also reported exhaustion, diminished endurance for exercise and trouble with even performing basic movements, such as picking up a towel or even raising his legs. He also noticed diffuse fasciculations that occurred a few times per day bilaterally in his arms and legs, along with possible eyebrow twitching, but which did not progress.

Before coming to RUSH, he was seen by three other outside neurologists who did not provide him with a clear diagnosis. His electromyography (EMG) results were reportedly normal with no clear evidence of neuropathy, neuron disease or myopathy; antibodies for myasthenia gravis were negative.

Presentation and Examination

His examination showed decreased facial strength, tongue weakness (worse on the right), neck flexion and weakness in the deltoid, right triceps, hip flexors, hip adductors, abductor pollicis brevis and rhomboids. He also had moderate thoracic scoliosis, mild right pectoral atrophy, a few fasciculations in the left proximal arm and moderately diminished vibration in the hallux bilaterally.

His electrophysiologic tests were abnormal. They indicated the patient had a chronic myopathy without membrane irritability, along with chronic partial denervation in the right upper extremity, which was consistent with a chronic right cervical motor radiculopathy at C6-C7.

Following this initial data, I scheduled the patient for an MRI of the brain and cervical spine, further bloodwork (CK, SPEP, MuSK antibody, paraneoplastic panel, and a 59-gene comprehensive muscular dystrophy panel) and a referral to a pulmonologist.

All of the patient’s bloodwork was normal.

The MRI of his brain and cervical spine revealed the following:

1. Fatty replacement of the tongue. The degenerative changes at the craniovertebral junction were mild. The hypoglossal canals were uninvolved.
2. S-shaped mild scoliosis of the cervicothoracic spine with cervical-dextro convexity at C6-C7. The patient also had slight cervical kyphosis centered at C6-C7 with mild anterolisthesis of C5. There were multilevel degenerative disc and endplate changes with uncovertebral and facet arthropathy.
3. The patient also had moderate spinal canal stenosis at C5-C6 and C6-C7, mild-to-moderate spinal canal stenosis at C4-C5 and varying degrees of foraminal narrowing at multiple levels as I detailed above.

The gene comprehensive muscular dystrophy panel found two pathogenic variants in the GAA gene. Both GAA variants are known to be associated with late-onset Pompe disease (LOPH).

In addition, his pulmonology tests showed restrictive lung disease as a result of having Pompe disease.

Based on the data, I recommended that we treat the patient with enzyme replacement therapy, the only available treatment for this condition.

What is Pompe disease?

Pompe disease is a rare type of genetic disorder that causes progressive weakness to the heart and skeletal muscles. For patients who have this disease, they have either an absence or deficiency in acid alfa glucosidase (GAA), which aids in breaking down glycogen. When glycogen builds up in the body, it can cause damage to skeletal and heart muscles.

Patients can either have early or late-onset Pompe disease. The early-onset form causes infants to have several challenges with feeding, weight gain, breathing and muscle weakness, among others. Without enzyme therapy, patients will typically die before turning 1-year old.

Those with LOPH can develop the condition as a juvenile or adult. Over time, muscle weakness leads to respiratory failure, then eventually death.

The National Institutes of Health estimate that 1 in every 40,000 people is affected by this disease in the United States.

Treatment

As part of the patient’s comprehensive care plan, we implemented several therapies to stabilize and hopefully improve his condition.

1. The patient began enzyme replacement therapy (ERT) initially with Lumizyme (alglucosidase alfa) infusions every two weeks and then with Nexviazyme (avalglucosidase alfa-ngpt) infusions, twice weekly, when it received FDA approval in 2021.
   ERT in Pompe disease helps to improve glycogen clearance from muscle tissues by lysosomes with a significant improvement in patient’s ability to ambulate and breathe with improvements noted as early as 13 weeks after treatment. Long-term data suggests that this benefit persists even after two years of treatment.
2. In addition to ERT, management of Pompe disease involves supportive care. Given the wide array of clinical manifestations, it is best managed in a multidisciplinary clinic. This patient was seen in the comprehensive Muscular Dystrophy Association (MDA) care clinic at RUSH. He met with our physical and occupational therapists who discussed strategies for energy conservation, avoiding falls and establishing a home exercise program.
3. He met with our speech-language therapist to address his difficulties chewing, jaw and tongue weakness and challenges with speech. Safe-swallowing strategies and implementation of expiratory muscle strength training device were discussed.
4. After a consultation with a dietician, the patient began eating a high-protein, high-fiber carbohydrate diet, which included two-to-four servings of fruits and vegetables, along with adequate hydration.
5. The pulmonology team also provided the patient with iVAPS ventilation to improve his breathing at night. Ultimately, the patient will be given transcutaneous CO2 and Oxide/Nitride/Oxide (ONO) to help wean him off nocturnal oxygen.

Outcome

At the last clinic visit in June 2023, the patient was noted to have a significant improvement in his pulmonary function test numbers compared to 2021. He felt that he needed his iVAPS less. He reported that he still was able to enjoy long bike rides.

Analysis

Pompe disease is a rare lysosomal disease. Diagnosis of this condition in adults can be delayed as it can cause a wide range of symptoms that can mimic other ailments. Experienced neuromuscular physicians at tertiary care centers, such as RUSH, are adept at recognizing rare neuromuscular illnesses.

Diagnosis of genetic neuromuscular illnesses should not be missed and currently we have novel therapies, such as ERT and gene therapies, to treat them. Quality and quantity of life for these individuals are improved by the supportive management provided by a multidisciplinary specialized clinic. RUSH is one of six adult MDA-funded clinics in Illinois that offers a comprehensive care model for individuals with neuromuscular diseases.