eliglustat-tartrate and Lung-Diseases--Obstructive

Fabry disease is an X-linked disease due to a deficiency of the lysosomal enzyme alpha-galactosidase A. Clinical symptoms in classically affected males include acroparesthesia, anhydrosis and angiokeratoma, which may present during childhood followed by cardiac, cerebral and renal complications. Even though pulmonary involvement is not widely appreciated by clinicians, an obstructive lung disease is another recognized component of Fabry disease. Coronavirus Disease-19 (COVID-19), caused by the SARS-CoV-2 virus was labeled as a global pandemic and patients with Fabry disease can be considered at high risk of developing severe complications. The impact of COVID-19 on patients with Fabry disease receiving enzyme replacement therapy is still unknown. Many patients who receive treatment in the hospital experienced infusion disruptions due to fear of infection. Effects of temporary treatment interruption was described in more detail in other lysosomal storage diseases, but the recommencement of therapy does not fully reverse clinical decline due to the temporary discontinuation. When possible, home-therapy seems to be the most efficient way to maintain enzyme replacement therapy access during pandemic. Sentence take-home message: Home-therapy, when possible, seems to be the most efficient way to maintain enzyme replacement therapy access during pandemic in patients with Fabry disease.

Topics: Adult; alpha-Galactosidase; Betacoronavirus; Continuity of Patient Care; Coronavirus Infections; COVID-19; Enzyme Replacement Therapy; Fabry Disease; Female; Home Infusion Therapy; Humans; Infection Control; Infusions, Intravenous; Isoenzymes; Lung Diseases, Obstructive; Male; Middle Aged; Pandemics; Pneumonia, Viral; Recombinant Proteins; SARS-CoV-2; Severity of Illness Index; Time Factors

Fabry disease is an X-linked glycosphingolipidosis caused by a deficiency of α-galactosidase A, a lysosomal enzyme. Symptoms in hemizygous males and heterozygous females are due to lysosomal storage of globotriaosylceramide in the central and peripheral nervous system, vascular endothelium, cardiac valves and myocytes, gastrointestinal tract, and renal epithelium. Pulmonary involvement is also a recognized manifestation of Fabry disease, but histopathological evidence of pulmonary lysosomal storage is scant. We report a 51-year-old woman with a G43R α-galactosidase A mutation and normal spirometry testing 2.5 years prior to presentation, who experienced a dry, nonproductive cough that persisted despite treatment with antibiotics and bronchodilators. Spirometry demonstrated a mixed restrictive/obstructive pattern as well as impaired gas exchange. Patchy ground-glass pulmonary interstitial infiltrates were found on plain radiography and computerized tomography. She underwent an open lung biopsy that demonstrated peribronchiolar fibrosis and smooth-muscle hyperplasia. Prominent inclusion bodies of the bronchiolar/arteriolar smooth muscle and endothelium were present. Electron microscopy indicated the inclusion bodies were lamellated zebra bodies consistent with globotriaosylceramide storage. Enzyme replacement therapy (ERT) with agalsidase-beta was instituted. Since initiation of therapy, she occasionally has a dry cough but markers of obstructive lung disease have remained stable in the past 4 years. This report demonstrates that pulmonary involvement in Fabry disease is due to lysosomal storage, and suggests that ERT is capable of stabilizing pulmonary Fabry disease. However, progressive worsening of her total lung capacity indicates that ERT cannot reverse the ongoing process of fibrosis also seen in Fabry disease.

Topics: alpha-Galactosidase; Biopsy; DNA Mutational Analysis; Enzyme Replacement Therapy; Fabry Disease; Female; Humans; Isoenzymes; Lung; Lung Diseases, Obstructive; Middle Aged; Pulmonary Fibrosis; Respiratory Function Tests; Tomography, X-Ray Computed; Treatment Outcome; Trihexosylceramides