CHEST Guidelines-Two-Siblings-With-Interstitial-Lung-Disease

Two-Siblings-With-Interstitial-Lung-Disease_chest

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The document presents a case study of two siblings diagnosed with interstitial lung disease (ILD), attributed to Niemann-Pick disease type B. The siblings, a 52-year-old woman and her 61-year-old brother, both experienced gradually worsening symptoms such as exertional dyspnea and cough. Medical histories include different environmental exposures but no smoking, connective tissue diseases, or medication-related ILDs.<br /><br />Both patients showed normal lung volumes with moderately impaired gas transfer on pulmonary function tests. Imaging demonstrated distinct lung patterns for each sibling; the woman showed interlobular septal thickening without specific features like honeycombing, whereas the man had upper lobe-predominant paraseptal emphysema, among other features. Histopathologic analysis of lung tissue in both patients revealed an accumulation of lipid-laden histiocytes and a diagnosis of acid sphingomyelinase deficiency was confirmed through enzyme activity and genetic tests demonstrating the R610del mutation in the SMPD1 gene.<br /><br />Niemann-Pick disease types A and B arise from mutations in the SMPD1 gene. Type B, affecting the siblings, is a milder form without neurological symptoms but accompanies extrapulmonary signs such as splenomegaly, hepatomegaly, and lipid-laden macrophages in tissues, including the lungs. This disease occurs along a phenotypic spectrum influenced by residual enzyme activity, with the two siblings exhibiting ILD and the structural abnormalities identified in chest CTs.<br /><br />Currently, therapeutic options include supportive care, while ongoing clinical trials explore recombinant enzyme replacement therapies. The case highlights the importance of recognizing phenotypic variability within familial ILD manifestations and considering underlying genetic predispositions. The presence of systemic clues beyond respiratory symptoms aids in diagnosing such rare genetic conditions.

Keywords

interstitial lung disease

Niemann-Pick disease type B

R610del mutation

SMPD1 gene

lipid-laden histiocytes

acid sphingomyelinase deficiency

phenotypic spectrum

enzyme replacement therapy

familial ILD

genetic predispositions