Late-Onset Pompe Disease With Left-Sided Bronchomalacia

Abstract

Pompe disease is a rare autosomal recessive disorder caused by ␣-glucosidase deficiency. Lower airway involvement and management are rare in patients with late-onset Pompe disease. We describe the case of a 16-y-old girl with late-onset Pompe disease who presented with obvious progressive deterioration in respiratory function. Pulmonary hypertension was also apparent on echocardiography. She had been on enzyme replacement therapy and nighttime CPAP ventilation for several years. Flexible bronchoscopy was used for diagnosis and subsequent implantation of a bronchial airway stent. Following implantation of the stent, the patient's pulmonary function stabilized, and her pulmonary hypertension resolved. The patient continued on enzyme replacement therapy and nighttime CPAP ventilation. This case highlights that lower airway involvement may occur with lateonset Pompe disease and that flexible bronchoscopy can be an effective tool for both diagnosis and management of lower airway collapse in late-onset Pompe disease.

Airway abnormalities in very early treated infantile‐onset Pompe disease: A large‐scale survey by flexible bronchoscopy

“…All the above descriptions might relate to the dysphonia, sleep-disordered breathing, decreased cough, impaired airway clearance, and other respiratory illnesses (Bay et al, 2019;McCall & ElMallah, 2019;Owens et al, 2018;Turner et al, 2016;Yang et al, 2014). (Yang et al, 2014(Yang et al, , 2015.…”

“…Evaluation of speech disorders in our patients suggested varying degrees of hypernasal resonance, consonant substitution, consonant omission, and consonant distortion in all patients 3 years of age and older, even with very early and regular ERT. Previous studies of patients with IOPD suggest speech disorders with consonant substitutions, consonant omissions, cluster reductions, mild to moderate hypernasal resonance, hoarseness, and a wet voice (Yang et al, , , ). The speech defect could be due to the compromised muscle strength in the oral cavity and the oropharynx.…”

The Respiratory Phenotype of Pompe Disease Mouse Models

“…As summarized above, there is significant glycogen accumulation in the bronchial and tracheal smooth muscle tissue of Pompe mice, resulting in reduced airway patency [67]. Similarly, studies of IPD and LOPD patients show glycogen accumulation in the trachea, bronchi, and bronchioles, which leads to trachea-bronchomalacia and an inability to maintain an open airway [25,84,85]. This malacia exacerbates respiratory insufficiency since the smaller airway radius results in increased resistance to airflow.…”

“…Therefore, the currently available ERT treatment with rhGAA may not effectively target neural tissue [83] because rhGAA cannot cross the blood-brain barrier. Furthermore, although ERT has significantly improved survival and quality of life of patients with Pompe disease, some patients on ERT still have mild to moderate accumulation of glycogen in the diaphragm [84], intercostal muscles [84], and airway smooth muscle [25,85] and pathology in respiratory control neurons [85]. Therefore, novel therapies need to target both muscle and neuronal pathology in order to treat the respiratory dysfunction.…”

“…ERT improves survival by clearing glycogen in cardiac muscle and improving cardiac function. However, because ERT does not effectively clear glycogen in respiratory skeletal muscle, airway smooth muscle, and neural control centers, many patients on ERT still suffer from respiratory dysfunction and require ventilatory support [6,8,[20][21][22][23][24][25]. Recent advances in gene therapy hold promise for treating Pompe disease, as gene therapy has the potential to ameliorate respiratory insufficiency [6,8,[26][27][28][29][30].…”