Niemann-Pick Type B: A Rare Cause of Interstitial Lung Disease

Abstract

Niemann-Pick disease (NPD) is a rare lysosomal storage disease (LSD) with multisystemic involvement. The disease is heterogeneous and classified into three subtypes: type A and B result from deficient acid sphingomyelinase activity and leads to the accumulation of sphingomyelin and type C is a genetically different disease resulting from defective intracellular trafficking of cholesterol with accumulation of glycosphingolipids. Type A is generally a neurodegenerative disease and is fatal in infancy. Type B is a less severe form characterized by pulmonary involvement, hepatosplenomegaly, hyperlipidemia and most patients live into adulthood. In type C, clinical presentation is dominated with neurological involvement. Pulmonary involvement occurs in all three types of Niemann-Pick but most frequently in type B. Clinical manifestations range from a lack of symptoms to respiratory failure, and respiratory symptoms are usually mild with recurrent cough, dyspnoea on exertion and recurrent respiratory infections. Interstitial lung disease (ILD) is the most prominent feature with slow progression, characterized by worsening pulmonary function tests. In recent years, enzyme replacement therapy has shown promising results in clinical trials, such as improvement in organomegaly and pulmonary involvement with the potential to improve patients' lives. We present three cases of NPD with pulmonary involvement, each exhibiting a different pattern of ILD and evaluate therapeutic options.

Case report: One pediatric liver-transplant recipient with SARS-CoV-2 infection suffering unexplained mixed acidosis

“…Niemann-Pick disease is an uncommon autosomal recessive inherited disease which could affect multiple organs including liver, spleen, lung and other macrophage-abundant organs ( 13 ). Previous reports of NPD type B cases showed that interstitial lung lesions are common ( 14 ). The girl’s X-ray showed interstitial changes leading to CO 2 retention, which may explain the respiratory acidosis.…”

The Long-term Lung and Respiratory Outcomes of Acid Sphingomyelinase Deficiency: A 10- and 20-year Follow-up Study

“…In the lungs, excess sphingomyelin accumulation in alveolar macrophages impairs their normal function, causing a buildup of surfactant lipids and proteins in the alveoli known as pulmonary alveolar proteinosis (3,10). The alveoli become filled with lipoproteinaceous material, impairing gas exchange and causing respiratory symptoms that can ultimately lead to respiratory failure if untreated due to impaired diffusion capacity and ventilation-perfusion mismatch (10)(11)(12)(13).…”