目的: 通过1例以血小板减少、骨密度增高为主要表现的恶性常染色体隐性遗传骨硬化症(ARO)患儿的病例报告, 以期加强对ARO临床表现及基因型特点的认识, 从而提高该病诊治水平。方法: 结合1例新生儿恶性ARO患儿临床诊治过程及相关文献报道, 对该病病因、临床表现、基因型特点及诊治进行讨论。结果: 22日龄男婴因发热2 d、发现皮肤出血点1 d为主诉入院, 查体颜面部可见散在出血点, 按压不褪色, 查血小板23×109 L-1, X线胸片示肋骨骨质密度增高, CLCN7基因检测发现存在chr16:1506200 c.824_830delTCTTCGA移码突变复合杂合7-17号外显子重复突变, 该类型基因突变国内外尚未见报道。患儿移码突变源于其父亲, CNV重复突变遗传自其母亲, 且其父母均未发病, 根据基因型及患儿表型确诊为ARO。经对症及支持等治疗后患儿病情好转, 但出院后未至门诊复查, 1个月后死亡。结论: 对于新生儿不明原因的发热、血小板减少, 除外常见原因, 需警惕罕见病因, 如新生儿恶性ARO, 应积极完善相关基因检测, 以免漏诊误诊、延误治疗。 |
[1] STARK Z, SAVARIRAYAN R. Osteopetrosis[J]. Orphanet J Rare Dis, 2009, 4(1): 5.
[2] SUPERTI-FURGA A, UNGER S. Nosology and classification of genetic skeletal disorders: 2006 revision[J]. Am J Med Genet A, 2010, 143a(1): 1-18.
[3] TOLAR J, TEITELBAUM S L, ORCHARD P J. Mechanisms of disease: osteopetrosis[J]. Human Genetics, 2004, 351(27): 2839-2849.
[4] BALEMANS W, WESENBEECK L V, HUL W V. A clinical and molecular overview of the human osteopetroses[J]. Calcif Tissue Int, 2005, 77(5): 263-274.
[5] BLIZNETZ E A, TVERSKAYA S M, ZINCHENKO R A, et al. Genetic analysis of autosomal recessive osteopetrosis in Chuvashiya: the unique splice site mutation in TCIRG1 gene spread by the founder effect[J]. Eur J Hum Genet, 2009, 17(5): 664-672.
[6] PHADKE S R, FISCHER B, GUPTA N, et al. Novel mutations in Indian patients with autosomal recessive infantile malignant osteopetrosis[J]. Indian J Med Res, 2010, 131(4): 508-514.
[7] BESBAS N, DRAAKEN M, LUDWIG M, et al. A novel CLCN7 mutation resulting in a most severe form of autosomal recessive osteopetrosis[J]. Eur J Pediatr, 2009, 168(12): 1449-1454.
[8] PANGRAZIO A, CALDANA M E, SOBACCHI C, et al. Characterization of a novel Alu-Alu recombination-mediated genomic deletion in the TCIRG1 gene in five osteopetrotic patients[J]. J Bone Miner Res, 2009, 24(1): 162-167.
[9] SHAPIRO F. Osteopetresis: current clinical considerations[J]. Clin Orthop, 1993, 294(294): 34-44.
[10] LORÍACORTÉS R, QUESADACALVO E, CORDEROCHAVERRI C. Osteopetrosis in children: a report of 26 cases[J]. J Pediatr, 1977, 91(1): 43-47.
[11] GERRITSEN E J A, VOSSEN J M, LOO I H G V, et al. Autosomal recessive osteopetrosis: variability of findings at diagnosis and during the natural course[J]. Pediatrics, 1994, 93(2): 247-253.
[12] FRATTINI A, PANGRAZIO A, SUSANI L, et al. Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis[J]. J Bone Miner Res, 2003, 18(10): 1740-1747.
[13] 刘权中, 崔清波, 贾学渊, 等. 骨硬化症临床表现与遗传致病性[J]. 国际遗传学杂志, 2020, 43(1): 46-51.
[14] DRIESSEN G, GERRITSEN E, FISCHER A, et al. Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report[J]. Bone Marrow Transpl, 2003, 32(7): 657-663.
[15] ORCHARD P J, FASTH A L, LE RADEMACHER J, et al. Hematopoietic stem cell transplantation for infantile osteopetrosis[J]. Blood, 2015, 126(2): 270-276.
[16] 程健豪, 汪纯, 章振林. 氯离子通道蛋白7相关骨硬化症[J]. 中华骨质疏松和骨矿盐疾病杂志, 2017, 10(5): 491-498.
[17] KORNAK U, SCHULZ A, FRIEDRICH W, et al. Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis[J]. Human Molecular Genetics, 2000, 9(13): 2059-2063.
[18] WADA K, HARADA D, MICHIGAMI T, et al. A case of autosomal dominant osteopetrosis type Ⅱ with a novel TCIRG1 gene mutation[J]. J Pediatr Endocrinol Metab, 2013, 26(5-6): 575-577.
[19] SOBACCHI C. The mutational spectrum of human malignant autosomal recessive osteopetrosis[J]. Hum Mol Genet, 2001, 10(17): 1767-1773.
[20] 胡彬, 曾秉辉, 胡悦林, 等. 一例罕见的新的TCIRG1基因杂合性突变引起的婴儿恶性石骨症[J]. 中国病理生理杂志, 2015, 31(7): 1237-1241. |