The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann-Pick Disease: A Comprehensive Review

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2024-02, Vol.14 (2), p.211
• Main Authors: Tirelli, Claudio, Rondinone, Ornella, Italia, Marta, Mira, Sabrina, Belmonte, Luca Alessandro, De Grassi, Mauro, Guido, Gabriele, Maggioni, Sara, Mondoni, Michele, Miozzo, Monica Rosa, Centanni, Stefano
• Format: Article
• Language: English
• Subjects: acid sphingomyelinase deficiency; Acids; Alveoli; Biopsy; Brain diseases; Bronchoscopy; Care and treatment; Cholesterol; Computed tomography; Development and progression; Enzymes; Esterification; Genetic aspects; Genetic disorders; Genotype & phenotype; Health aspects; Hematopoietic stem cells; Humans; Lipids; Lung - metabolism; Lung diseases; Lung Diseases - genetics; Lung Diseases - therapy; Lung transplantation; Lungs; Lysosomal storage diseases; Metabolic disorders; Mutation; Neural coding; Niemann-Pick disease; Niemann-Pick Disease, Type A - genetics; Niemann-Pick Disease, Type A - metabolism; Niemann-Pick Disease, Type A - therapy; Niemann-Pick Disease, Type B - genetics; Niemann-Pick Disease, Type B - therapy; Niemann-Pick Diseases - genetics; Niemann-Pick Diseases - therapy; NPC1; Npc1 protein; NPC2; Olipudase α; Rare Diseases; Search engines; SMPD1; Sphingomyelin phosphodiesterase; Stem cell transplantation
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom14020211

Niemann-Pick Disease (NPD) is a rare autosomal recessive disease belonging to lysosomal storage disorders. Three types of NPD have been described: NPD type A, B, and C. NPD type A and B are caused by mutations in the gene coding for sphingomyelin phosphodiesterase 1, with a consequent lack of acid sphingomyelinase activity. These diseases have been thus classified as acid sphingomyelinase deficiencies (ASMDs). NPD type C is a neurologic disorder due to mutations in the genes or , causing a defect of cholesterol trafficking and esterification. Although all three types of NPD can manifest with pulmonary involvement, lung disease occurs more frequently in NPD type B, typically with interstitial lung disease, recurrent pulmonary infections, and respiratory failure. In this sense, bronchoscopy with broncho-alveolar lavage or biopsy together with high-resolution computed tomography are fundamental diagnostic tools. Although several efforts have been made to find an effective therapy for NPD, to date, only limited therapeutic options are available. Enzyme replacement therapy with Olipudase α is the first and only approved disease-modifying therapy for patients with ASMD. A lung transplant and hematopoietic stem cell transplantation are also described for ASMD in the literature. The only approved disease-modifying therapy in NPD type C is miglustat, a substrate-reduction treatment. The aim of this review was to delineate a state of the art on the genetic basis and lung involvement in NPD, focusing on clinical manifestations, radiologic and histopathologic characteristics of the disease, and available therapeutic options, with a gaze on future therapeutic strategies.