Patients diagnosed with non-classic Pompe disease may suffer from aggravated symptoms if they have a history of the cardiological disorder. They may suffer from certain vascular abnormalities, such as arterial dissections, vertebrobasilar dolichoectasia, and aneurysms. Severe hypertrophic cardiomyopathy, respiratory failure, and generalised hypotonia are main features in infantile form of Pompe disease. Adults may manifest Pompe disease with stiffness and other stressors. Studies suggest that glycogen may accumulate within smooth muscle cells and endothelial cells leading to changes in the arterial wall.

Various studies conducted worldwide showed abnormal cardiac findings in patients with a history of cardiac diseases. They may manifest with symptoms like shortened PR interval, Wolf-Parkinson-White syndrome (WPWs), and right bundle branch block (RBBB). Moreover, as per studies conducted, some patients may have a larger mean aortic diameter and elevated left ventricular mass as seen on echocardiography.¹

Comorbidities Associated With Pompe Disease

In Pompe disease, steady accumulation of glycogen in tissues can lead to organ failure, progressive debilitation and death. It can also lead to a spectrum of disease severity. The severity can vary with the age of onset, organ involvement, and the degree and severity of muscle involvement. Due to the presence of muscle weakness and hypotonia, the disease can resemble neuromuscular disease or metabolic myopathy. The infantile form of Pompe disease can cause hepatomegaly, prominent cardiomegaly, weakness, and hypotonia. Non-classic form can have comorbidities related to musculoskeletal disorders, such as rigid spine syndrome, limb-girdle weakness and exercise intolerance. They also present with gastrointestinal features like difficulty swallowing and feeding, poor weight gain.² 

Late-onset Pompe disease (LOPD) is considered a multisystem disorder. Patients suffer from progressive muscle weakness and respiratory insufficiency leading to premature disability, supported ventilation, and eventually leading to death. Patients may also witness exercise intolerance, myalgia, and postural weakness, such as difficulty in walking, running, climbing stairs, or standing up from the floor. 

Patients have central and peripheral nerve disorders due to the accumulation of lysosomal glycogen in smooth muscles, anterior horn cells, and peripheral nerves. Multisystem LOPD patients may manifest with temperature alterations and neuropathic pain due to glycogen deposition in the Schwann cells of the peripheral nervous system. It can also result in autonomic dysfunction leading to dry eyes, orthostasis, gastrointestinal (GI) dysfunction, and sexual dysfunction.³

Infants Suffering From Pompe Disease

Infants before 6 months of age diagnosed with Pompe disease may develop progressive and massive cardiomegaly due to glycogen accumulation in cardiac muscle causing thickening of walls of both ventricles and interventricular septum. It can lead to hypertrophic cardiomyopathy eventually progressing to dilated cardiomyopathy. Increased left ventricular thickness can lead to obstruction of left ventricular outflow. As per studies conducted, autopsy of the infant form of Pompe disease showed that the heart was three times its normal size with endocardial fibroelastosis. Electrocardiography of such findings shows that the PR interval is shortened with a widened QRS complex which is typical of Pompe disease and differentiates from other causes of cardiac disease in infants.⁴

Early Onset Comorbidities With Pompe Disease

Patients face difficulties while speaking and swallowing their food as they suffer from oropharyngeal muscle weakness. Assessment of speech and swallowing is critical to identify the symptoms associated with the early onset of Pompe disease. Patients having respiratory distress are prone to muscle weakness as well. There is an increased risk for aspiration with decreased reserve for concurrent cardiac disease. 

Non-invasive respiratory support is warranted for all children with a new diagnosis of Pompe disease. Moreover, patients with a history of ventricular arrhythmias or cardiovascular collapse should be cautious as they are recommended to avoid dehydration and hypotension. Patients with the past medical history of congestive heart failure and supraventricular tachyarrhythmias should be cautious as well.⁵

Patients with a past medical history of respiratory muscle weakness become more fragile as the disease progresses. Spirometry and oxygen saturation tests should be conducted to monitor their respiratory function. Arterial blood gas (ABG) tests should be performed annually to see changes in the respiratory status. Patients with Pompe disease develop alterations during gas exchange and they might experience respiratory disturbances while sleeping. They can be assisted through mechanical coughing techniques, including respiratory physiotherapy. Positive pressure oxygen therapy should be applied to avoid hypoventilation, hypoxemia, and obstructive sleep apnea.⁶

References

  1. H.A. van Kooten , C.H.A. Roelen , E. Brusse , et al.  Cardiovascular disease in non-classic pompe disease: a systematic review., Neuromuscular Disorders. 2020, doi: https://doi.org/10.1016/j.nmd.2020.10.009
  2. Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. published correction appears in Genet Med. 2006 Jun;8(6):382. ACMG Work Group on Management of Pompe Disease; Case, Laura [corrected to Case, Laura E]]. Genet Med. 2006;8(5):267-288. doi:10.1097/01.gim.0000218152.87434.f3
  3. Toscano A, Rodolico C, Musumeci O. Multisystem late onset pompe disease (LOPD): an update on clinical aspects. Annals of translational medicine. 2019 Jul;7(13).
  4. Kishnani PS, Howell RR. Pompe disease in infants and children. The Journal of pediatrics. 2004 May 1;144(5):S35-43.
  5. Morales JA, Anilkumar AC. Glycogen storage disease type II. Updated 2021 May 4. In: StatPearls. 2021 Jan-.https://www.ncbi.nlm.nih.gov/books/NBK470558/
  6. Barba-Romero MA, Barrot E, Bautista-Lorite J, Gutierrez-Rivas E,et al.  Clinical guidelines for late-onset Pompe disease. Rev Neurol. 2012 Apr 16;54(8):497-507.

Reviewed by Harshi Dhingra, MD, on 7/27/2021.

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