Osteoclast morphology in autosomal recessive malignant osteopetrosis due to a TCIRG1 gene mutation.
Bone biopsies were performed before and 7 weeks after transplantation of HLA-compatible bone marrow from the sister of a 3-month-old male infant with malignant autosomal recessive osteopetrosis due to a mutation in the TCIRG1 (ATP6i) gene. The first biopsy showed broad, immature bony trabeculae and no medullary hematopoiesis. Only few osteoclasts were present and electron microscopy showed absence of ruffled borders. The post transplant biopsy revealed donor osteoclasts with ruffled borders and intracytoplasmic mineral crystals as proof of active bone resorption that had not yet been detectable radiographically. Osteopetrosis is a genetically heterogeneous disease. Definition at the DNA-level will enable comparison of treatment strategies and prenatal diagnosis. As shown in this patient, the autosomal recessive form caused by a TCIRG1 gene mutation may be amenable to bone marrow transplantation. Activity of donor osteoclasts can be demonstrated morphologically on biopsy, before bone remodeling becomes evident radiologically.
Bruder
Elisabeth
E
Pediatric Pathology Section, Department of Pathology, University Hospital Zurich, Switzerland.
Stallmach
Thomas
T
Peier
Karin
K
Superti-Furga
Andrea
A
Vezzoni
Paolo
P
D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000473:pathology; D016026:Bone Marrow Transplantation; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008854:Microscopy, Electron; D009154:Mutation; D010010:Osteoclasts / Q000473:pathology* / Q000648:ultrastructure; D010022:Osteopetrosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D021122:Protein Subunits / Q000235:genetics; D014463:Ultrasonography; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics
D021122:Protein Subunits; C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases