[Pulmonary phenotypes of inborn errors of metabolism]

Abstract

Inborn metabolic diseases or inborn errors of metabolism comprise a large number of rare and heterogeneous genetic diseases categorized in several subgroups depending on their pathophysiologic mechanisms. In this review, we focus on different metabolic diseases with respiratory symptoms in adults: lysosomal glycosphingolipidoses such as acid sphingomyelinase deficiency (Niemann-Pick types A and B disease), Gaucher, Fabry, Pompe diseases and mucopolysaccharidoses in general. We also address classical homocystinuria, which is a monogenic vascular disease, Hermansky-Pudlak syndrome, which is associated with disorders in the lysosomal-related-organelles, and lysinuric protein intolerance, which is due to an amino-acid transporter defect. Presentation and prognosis of these diseases are highly heterogeneous, and respiratory impairment may be central and prognostic. Many are primarily pediatric, and diagnoses are often delivered during childhood. Improved pediatric management has enabled better prognosis and new phenotype of the diseases in the adulthood. Some others can be diagnosed during adulthood. While some diseases call for specific, specialized treatment, all necessitate systematic multidisciplinary management. It is of paramount importance that a pneumologist be familiar with these phenotypes, most of which can benefit from early diagnosis and early therapeutic management with dedicated innovative treatments.

Keywords: Acid sphingomyelinase deficiency; Diagnostic précoce; Déficit en prolidase; Fabry disease; Gaucher disease; Hermansky–Pudlak syndrome; Homocystinuria; Homocystinurie classique; Intolérance aux protéines dibasiques; Lysinuric protein intolerance; Maladie de Fabry; Maladie de Gaucher; Maladie de Niemann–Pick AB-B; Maladie de Pompe; Maltase acid deficiency; Mucopolysaccharidosis; Mucopolysasccharidoses; Prolidase deficiency; Syndrome d’Hermansky–Pudlak; Traitement; Treatment.