Pulmonary storage with emphysema as a sign of Niemann–Pick type C2 disease (second complementation group). Report of a case

Abstract

A case is described of Niemann-Pick type C2 disease presenting an infantile pneumopathic phenotype known to occur in this recently established, second, minor complementation group of Niemann-Pick type C (NPC) disease. However, the pulmonary involvement was unique, being dominated, in addition to the usual storage macrophage infiltration of the alveolar and septal compartments, by irregular emphysema attributed to storage cell migration into the bronchiolar lumen. The latter modified considerably the X-ray findings and hindered the initial clinical diagnosis. Otherwise, the storage phenotype, including the range of stored lipids, storage distribution, and cell and organ pathology, was found to be identical to that in the whole Niemann-Pick type C disease group dominated by NPC1. The biochemical findings (cholesterol esterification level) corresponded to the classical biochemical phenotype. Emphysema should thus be considered as a variant of the pulmonary NPC2 storage process, governed most probably by an epigenetic mechanism responsible for storage macrophage migration into the bronchiolar compartment.

Imaging of macrophage-related lung diseases

“…The lungs typically show a preserved architecture [86], and normally lack inflammation or fibrosis, although some authors have described "sclerotic" alveolar septa [87] as well as peribronchiolar and perivascular cuffs of connective tissue [88]. An intriguing but isolated case of emphysema caused by storage cell migration into the bronchiolar lumen has been reported [89].…”

Concurrent increase of cholesterol, sphingomyelin and glucosylceramide in the spleen from non‐neurologic Niemann–Pick type C patients but also patients possibly affected with other lipid trafficking disorders

“…Interestingly, the lipid pattern in raft microdomains [11–13] is similar to that found in visceral, in particular splenic NPC tissue [7] and the sphingolipids stored in NPC contain a high percentage of saturated fatty acyl chains [17], tight packing of such chains favouring raft formation [11,18]. Therefore, the possibility was considered that the NPC spleen lipid pattern with a concurrent accumulation of cholesterol, sphingomyelin, glucosylceramide (Acc‐CSG) and some other lipids [1,7,19] reflects a relatively unspecific accumulation of normal lipid membrane structures like the rafts, the Acc‐CSG lipid pattern suggesting a general affection of lipid trafficking involving rafts.…”

Lung cyst: An unusual manifestation of Niemann–Pick disease

“…Imaging features do not necessarily correlate with the degree of pulmonary function impairment in patients with subtype B NPD 2 . Two previous reports of NPD in children have described areas of low attenuation on HRCT consistent with emphysema 3–5 . This newly described pattern, ground‐glass opacities and cysts, is similar to that found in desquamative interstitial pneumonia 6 …”

“…This case report presents a patient with subtype B NPD characterized by ground‐glass opacities and cysts on HRCT of the chest. Pulmonary involvement in subtype B NPD may range from being asymptomatic to respiratory failure with oxygen dependence 1,3,4 Pulmonary function tests are often normal, except for decreased DL CO , as in this patient, with later development of a restrictive ventilatory defect 1 . The features of NPD on CXR are non‐specific and consist of diffuse reticular or reticulonodular infiltrates with basal predominance; later in the course of disease these may involve the entire lung field 2,3 …”

“…Subtype B is caused by a deficiency in acid sphingomyelinase activity and is characterized by hepatosplenomegaly, pulmonary and bone marrow involvement, without neurological deficit; it has an insidious course and a more benign prognosis. Pulmonary involvement is a major cause of morbidity and mortality in this subtype 1–3 …”