Title: Fabry Disease with Complex Restrictive Pulmonary Function Pattern

Author(s): Rasik Neupane, MD; Ashma Ul Husna, MD; Vipin D Villgran, MD

Email: rneupane@mercy.com

Introduction: Fabry disease is an X-linked inborn error of the glycosphingolipid metabolism caused by a deficiency of lysosomal hydrolase alpha-galactosidase A, resulting in intracellular accumulation of glycosphingolipids causing multisystemic disease. Complex Restriction (CR) is a pulmonary function pattern restriction not caused by a primary disorder of the lung parenchyma characterized by a disproportionately decreased Forced Vital Capacity percentage predicted (FVCpp) relative to the Total Lung Capacity percentage predicted (TLCpp). CR pattern is usually seen in neuromuscular disease, chest wall disorders, obesity, and diaphragmatic dysfunction. We present you with an unusual case of Fabry disease with pulmonary involvement with CR pulmonary function pattern from neuromuscular involvement.

Case Report(s): A 49-year-old male with Fabry disease presented with dyspnea. He was previously managed on agalsidase beta enzyme replacement therapy (ERT). Physical exam was significant for expiratory wheezes on auscultation. Prior laboratory investigations showed decreased alpha-galactosidase A (alpha-Gal A) activity. Computed tomography pulmonary angiography showed no pleuroparenchymal, vascular, diaphragmatic, or chest wall abnormalities. Cardiac workup with electrocardiography, echocardiography, and nuclear stress test was unremarkable. His body mass index was 17. A pulmonary function test (PFT) showed Obstruction with a Complex Restrictive pattern. He was treated with the Budesonide/Formoterol/Tiotropium combination and planned for additional ERT.

Discussion: It is hypothesized that patients with Fabry disease develop interstitial lung diseases from accumulation of glycosphingolipids in pulmonary alveoli leading to tissue remodeling and fibrosis. When the glycosphingolipids deposition and remodeling involve the bronchi, this can lead to chronic airway limitation and development of progressive airway obstruction. Similarly, intracellular glycosphingolipid accumulation also leads to neuropathy and skeletal myopathy.

Pulmonary function tests for Fabry disease mostly show obstructive airway disease, but occasionally, a restrictive or mixed pattern can be seen [3]. CR PFT pattern defined by TLCpp-FVCpp > 10% has never been described in Fabry patients. In our case, TLCpp-FVCpp was 38%. In our case, this CR pattern indicates both restriction and incomplete lung emptying from mechanical inability to reduce the volume of the thoracic cavity due to neuromuscular weakness [4]. Pulmonary presentations in Fabry disease are rare, and PFTs are crucial for diagnosis. CR pattern and FVCpp can be used to identify non-pulmonary causes of shortness of breath, especially in patients with concomitant neuromuscular involvement, and could potentially guide therapy and treatment response.