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A single‐center experience in 20 patients with infantile malignant osteopetrosis
Author(s) -
Mazzolari Evelina,
Forino Concetta,
Razza Alessia,
Porta Fulvio,
Villa Anna,
Notarangelo Luigi Daniele
Publication year - 2009
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.21447
Subject(s) - osteopetrosis , medicine , hypogammaglobulinemia , osteoclast , hematopoietic stem cell transplantation , transplantation , pediatrics , oncology , immunology , receptor , antibody
Infantile malignant osteopetrosis (IMO) includes various genetic disorders that affect osteoclast development and/or function. Genotype–phenotype correlation studies in IMO have been hampered by the rarity and heterogeneity of the disease and by the severity of the clinical course, which often leads to death early in life. We report on the clinical and molecular findings and treatment in 20 consecutive patients (11 males, nine females) with IMO, diagnosed at a single center in the period 1991–2008. Mean age at diagnosis was 3.9 months, and mean follow‐up was 66.75 months. Mutations in TCIRG1 , OSTM1 , ClCN7 , and TNFRSF11A genes were detected in nine, three, one, and one patients, respectively. Six patients remain genetically undefined. OSTM1 and ClCN7 mutations were associated with poor neurologic outcome. Among nine patients with TCIRG1 defects, six presented with hypogammaglobulinemia, and one showed primary pulmonary hypertension. Fourteen patients received hematopoietic cell transplantation; of these, nine are alive and eight of them have evidence of osteoclast function. These data may provide a basis for informed decisions regarding the care of patients with IMO. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.