Lung involvement in Niemann-Pick disease type C1: improvement with bronchoalveolar lavage

Abstract

Progressive lung infiltration is a major cause of death in Niemann-Pick disease type A and B (NPA, NPB) and in the recently defined type C2. In type C1 (NPC1), the main manifestations are neurological. We report a patient with a classic, neurological, late infantile form of NPC1 disease, carrying the mutation P474L and the variant I642M in the NPC1 gene, who suffered recurrent respiratory manifestations. Bronchoalveolar lavage of a lung segment due to deteriorating respiratory condition revealed many foamy macrophages and was followed by an improvement in symptoms. Pneumopathy may therefore be considered a feature of NPC1 disease for which a partial bronchoalveolar lavage could be a useful treatment.

Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease

“…This finding raised the possibility, therefore, that much of the unpredicted sequestration of cholesterol found in these organs came about because of LDL-TC clearance by the infiltrating macrophages as well as the parenchymal cells of the respective organs. As an aside, this same infiltration of lipid-laden macrophages is seen in the lungs of children with NPC disease and is described pathologically as "lipoid pneumonitis" (41).…”

“…Clinically, in the human, this cellular abnormality may be expressed as severe liver disease, pulmonary failure, chronic diarrhea, or progressive neurological disease (39)(40)(41)(42). The biochemical hallmark of this syndrome is an age-related, progressive accumulation of unesterified cholesterol in the cells of every organ (21,33,43).…”

Lysosomal unesterified cholesterol content correlates with liver cell death in murine Niemann-Pick type C disease

“…These patients may also present with recurrent pulmonary symptoms and even die of acute pulmonary failure. Histologically, these clinical symptoms are associated with extensive pulmonary infiltration by lipid-laden macrophages that is referred to as "endogenous lipid pneumonia" (12)(13)(14)(15). If the affected children escape these hepatic and pulmonary complications, they invariably develop evidence of progressive neurodegeneration.…”

Respiratory manifestations in patients with inherited metabolic diseases

“…A therapeutic role of BAL aimed at reducing the accumulation of abnormal metabolites within airways has been hypothesised in some inherited metabolic diseases, although its effectiveness is still under debate. In a patient with Niemann-Pick type C disease with recurrent pneumonia and chronic hypoxia, BAL significantly improved respiratory symptoms and ILD [34].…”

“…Routine HRCT should be recommended in cases with symptoms and signs suggestive of pulmonary disease that might benefit from whole lung lavage as treatment [34,35].…”