Niemann-Pick disease type C2 presenting as fatal pulmonary alveolar lipoproteinosis: morphological findings in lung and nervous tissue.
BACKGROUND
Niemann-Pick disease type C1 (NPC1) and type C2 (NPC2) display the same pattern of neurovisceral storage due to deficiencies within lysosomes. NPC2 is a much rarer condition, and as reports on the pathological changes are scarce, the morphological findings in the lungs and brain in two siblings who died at an early age from pulmonary involvement are described. The diagnosis of NPC2 was confirmed at postmortem mutational analysis.


METHODS
Both siblings presented with postnatal conjugated hyperbilirubinemia. They subsequently developed progressive respiratory insufficiency with opacification of the lungs on X-ray examination and died at the ages of 8 and 13 months. The lungs contained intra-alveolar accumulation of periodic acid-Schiff positive material, foamy macrophages, and hyperplasia of the alveolar cells, consistent with pulmonary alveolar lipoproteinosis. On neuropathological examination, storage material in swollen perikarya in the deep cerebellar nuclei, thalamus, medulla oblongata, and in the paravertebral ganglion cells was found. Meganeurites were present in the cerebral cortex. A few axonal spheroids were also observed. There seemed to be a reduced number of Purkinje cells in the cerebellum.


CONCLUSIONS
Evidence that NPC2 is associated with severe pulmonary alveolar lipoproteinosis is supported. There were extensive neuropathological changes with storage material in swollen perikarya and a few axonal spheroids.
Bjurulf
Björn
B
Department of Pediatrics, Ullevål University Hospital, Oslo, Norway.
Spetalen
Signe
S
Erichsen
Aage
A
Vanier
Marie T
MT
Strøm
Erik H
EH
Strømme
Petter
P
D002352:Carrier Proteins / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007223:Infant; D008065:Lipoid Proteinosis of Urbach and Wiethe / Q000150:complications*; D008297:Male; D009417:Nerve Tissue / Q000473:pathology*; D052556:Niemann-Pick Disease, Type C / Q000150:complications* / Q000235:genetics; D011650:Pulmonary Alveoli / Q000473:pathology* / Q000648:ultrastructure; D013902:Radiography, Thoracic; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D006023:Glycoproteins; C104585:NPC2 protein, human; D033921:Vesicular Transport Proteins