title: A single-center experience in 20 patients with infantile malignant osteopetrosis.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Brescia, 25123 Brescia, Italy. mazzolar@med.unibs.it
authors.forename: Evelina
authors.initials: E
authors.lastname: Mazzolari
authors.forename: Concetta
authors.initials: C
authors.lastname: Forino
authors.forename: Alessia
authors.initials: A
authors.lastname: Razza
authors.forename: Fulvio
authors.initials: F
authors.lastname: Porta
authors.forename: Anna
authors.initials: A
authors.lastname: Villa
authors.forename: Luigi Daniele
authors.initials: LD
authors.lastname: Notarangelo
mesh_terms: D000361:Agammaglobulinemia / Q000235:genetics / Q000401:mortality / Q000628:therapy; D018118:Chloride Channels / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000401:mortality / Q000628:therapy; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010022:Osteopetrosis / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics; D012189:Retrospective Studies; D015996:Survival Rate; D014184:Transplantation, Homologous; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics
chemical_list: C097540:CLCN7 protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; C489946:OSTM1 protein, human; D053246:Receptor Activator of Nuclear Factor-kappa B; C472421:TCIRG1 protein, human; C505686:TNFRSF11A protein, human; D044767:Ubiquitin-Protein Ligases; D025262:Vacuolar Proton-Translocating ATPases