Infantile Osteopetrosis and Juvenile Xanthogranuloma Presenting Together in a Newborn: A Case Report and Literature Review

• Published in: Pediatric and developmental pathology Vol. 14; no. 4; pp. 307 - 312
• Main Authors: Almarzooqi, Saeeda, Reed, Suzanne, Fung, Bonita, Boué, Daniel R., Prasad, Vinay, Pietryga, Daniel
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.07.2011; SAGE PUBLICATIONS, INC
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Biopsy; Humans; Infant, Newborn; Male; Membrane Glycoproteins - genetics; Osteopetrosis - complications; Osteopetrosis - genetics; Osteopetrosis - pathology; Xanthogranuloma, Juvenile - complications; Xanthogranuloma, Juvenile - genetics; Xanthogranuloma, Juvenile - pathology; juvenile xanthogranuloma; PLEKHM1 gene; infantile osteopetrosis
• ISSN: 1093-5266; 1615-5742
• DOI: 10.2350/10-09-0909-CR.1

Osteopetrosis (OP) is a clinically and genetically heterogeneous disorder characterized by increased bone density. Associations between OP and other clinical entities are rare but include muscular degeneration, Dandy-Walker syndrome, craniosynostosis, and poikiloderma. Infantile OP has also been diagnosed in a group of infants with neuronal storage disease. An association between OP and juvenile xanthogranuloma (JXG) has never been previously reported. Herein we present a case of an intermediate form of OP in a newborn who presented with hepatosplenomegaly and pancytopenia. Histologic evaluation of a bone marrow biopsy demonstrated abnormally thickened bony trabeculae. A liver biopsy demonstrated prominent expansion of portal areas by a histiocytic infiltrate expressing CD45, CD14, CD68, CD163, factor XIIIa, and fascin, while the biopsy was negative for S100 and CD1a. These findings were those associated with JXG. Genetic testing demonstrated a mutation involving the Pleckstrin homology domain-containing family M member 1 (PLEKHM1) gene. A different mutation in this gene has been previously reported in one other patient with OP. Our case is the 2nd reported case with PLEKHM1 mutation in a patient with a mild form of OP. It also demonstrates the 1st reported occurrence of OP concomitantly with JXG.