Lung biopsy is an invasive diagnostic method for the classification of diffuse parenchymal lung disease (DPLD) or so-called children's interstitial lung disease (chILD). Before lung biopsy, and solely based on the medical history and non-invasive diagnostics, the patient was classified as group A2 (DPLD-Growth abnormalities deficient alveolarization) and group B4 (DPLD-related to lung vessels structural processes) according to the Deutsch-Classification. We performed lung biopsy due to recurring severe respiratory infections, treated with multiple steroid pulses with moderate effects. Lung biopsy was performed by pediatric surgeons through a posterolateral mini-thoracotomy under general anesthesia without any complications, at the corrected age of 9 months. Histology confirmed BPD with hypoalveolarisation and an abnormal structure of the pulmonary vasculature with smooth muscle cell proliferation and altered extracellular matrix. A major histological finding was a variable pulmonary capillary hemangiomatosis (PCH), showing proliferating capillaries in row and grape-like formations around the alveolar septal tissue, that partly infiltrated alveolar septal tissue resulting in septal thickening. No participation or alteration of the pulmonary veins, particularly no obliterative fibrosis of the post-capillary venules was found. Small areas of the biopsy showed mild pulmonary interstitial glycogenosis (PIG) with cytoplasmic accumulation of glycogen in the interstitial cells (Figure 3).
Gentic testing by means of whole exom sequencing (WES) revealed a heterozygous mutation in the Endoglin (ENG) gene (c.172_1728del; p.{lle575del}) in the infant and the mother as a variant of unknown significance (VUS). There was no other pathogenic mutation in the following potential disease-causing genes (PH- and ILD-Panel): ABCA3, CSF2RW, FLNA, FOXF1, SFTPB, SFTPC, TBX4, ACVRL1, BMPR2, CAV1, EIF2AK4, GDF, KCNA5, KCNK3, SMAD4, SMAD9, AGPAT2, ALMS1, BSCL2, FOS, PPARG.