Mazzolari Evelina, Forino Concetta, Razza Alessia, Porta Fulvio, Villa Anna, Notarangelo Luigi Daniele
Department of Pediatrics, University of Brescia, 25123 Brescia, Italy.
Am J Hematol. 2009 Aug;84(8):473-9. doi: 10.1002/ajh.21447.
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.
婴儿恶性骨硬化症（IMO）包括多种影响破骨细胞发育和/或功能的遗传疾病。IMO的基因型-表型相关性研究受到该疾病的罕见性、异质性以及临床病程严重性的阻碍，临床病程严重往往导致患者早年死亡。我们报告了1991年至2008年期间在单一中心诊断的20例连续性IMO患者（11例男性，9例女性）的临床、分子学发现及治疗情况。诊断时的平均年龄为3.9个月，平均随访时间为66.75个月。分别在9例、3例、1例和1例患者中检测到TCIRG1、OSTM1、ClCN7和TNFRSF11A基因的突变。6例患者的基因情况仍不明确。OSTM1和ClCN7突变与不良神经学预后相关。在9例TCIRG1缺陷患者中，6例出现低丙种球蛋白血症，1例表现为原发性肺动脉高压。14例患者接受了造血细胞移植；其中9例存活，8例有破骨细胞功能证据。这些数据可为IMO患者的治疗决策提供依据。
