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先天性聋哑患儿伴面色苍白、贫血1年
Congenital deaf-mutism with pale complexion and anemia for 1 year in a school-aged girl
患儿女，11岁，发现面色苍白、贫血逐渐加重1年，既往体质较弱，每年约3~5次右中肺肺炎病史，予抗感染治疗后可好转。患儿及其母亲均为先天性聋哑。体格检查可见贫血貌，无出血、黄疸、肝脾大和淋巴结肿大等表现，血常规提示三系减少，为正细胞性贫血，骨髓中粒红系有巨幼样变，未见明显原始细胞增多及其他转移瘤细胞，全外显子组测序提示存在已知ES致病突变：GATA2基因c.1084C > T（p.Arg362*）。该患儿最终确诊为ES，随访发现由MDS最终转化为AML。ES为罕见的常染色体显性遗传MDS，临床不多见，诊断较困难。建议对不明原因淋巴水肿、先天性耳聋，要警惕ES可能，应进一步完善相关基因检查明确诊断。
An 11-year-old girl was found to have pale complexion and anemia with gradual aggravation for one year. She was weak in the past and developed pneumonia in the right middle lung 3-5 times per year, which was improved after anti-infective therapy. She and her mother had congenital deaf-mutism. Physical examination showed the appearance of anemia, without bleeding, jaundice, hepatosplenomegaly, or lymph node enlargement. Routine blood test results showed reductions in all three blood cell lines, normocytic anemia, and megaloblastoid change in granulocytic and erythroid cell lines in bone marrow, with no obvious increase in primitive cells or metastatic tumor cells. Whole exome sequencing indicated the presence of a known pathogenic mutation for Emberger syndrome (ES), c.1084C > T (p.Arg362*) in the GATA2 gene. The girl was finally diagnosed with ES, and myelodysplastic syndrome (MDS) progressed to acute myeloid leukemia during follow-up. ES is a rare type of MDS with autosomal dominant inheritance in clinical practice, and it is difficult to make a confirmed diagnosis. ES should be considered for children with unexplained lymphedema and congenital deafness, and gene detection should be performed to make a confirmed diagnosis.
Emberger综合征 / GATA2基因 / 先天性耳聋 / 骨髓增生异常综合征 / 急性髓系白血病 / 学龄期儿童
Emberger syndrome / GATA2 gene / Congenital deafness / Myelodysplastic syndrome / Acute myelogenous leukemia / School-aged child
[1] Saida S, Umeda K, Yasumi T, et al. Successful reducedintensity stem cell transplantation for GATA2 deficiency before progression of advanced MDS[J]. Pediatr Transplant, 2016, 20(2):333-336.
[2] Nováková M, ?aliová M, Suková M, et al. Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome[J]. Haematologica, 2016, 101(6):707-716.
[3] Emberger JM, Navarro M, Dejean M, et al. Deaf-mutism, lymphedema of the lower limbs and hematological abnormalities (acute leukemia, cytopenia) with autosomal dominant transmission[J]. J Genet Hum, 1979, 27(3):237-245.
[4] Rakhmanov Y, Maltese PE, Paolacci S, et al. Genetic testing for Emberger syndrome[J]. EuroBiotech J, 2018, 2:19-21.
[5] Hsu AP, Sampaio EP, Khan J, et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome[J]. Blood, 2011, 118(10):2653-2655.
[6] Zawawi F, Sokolov M, Mawby T, et al. Emberger syndrome:a rare association with hearing loss[J]. Int J Pediatr Otorhinolaryngol, 2018, 108:82-84.
[7] Michelini S, Cardone M, Haag M, et al. A rare case of Emberger syndrome caused by a de novo mutation in the GATA2 gene[J]. Lymphology, 2016, 49(1):15-20.
[8] Spinner MA, Sanchez LA, Hsu AP, et al. GATA2 deficiency:a protean disorder of hematopoiesis, lymphatics, and immunity[J]. Blood, 2014, 123(6):809-821.
[9] Mutsaers PG, van de Loosdrecht AA, Tawana K, et al. Highly variable clinical manifestations in a large family with a novel GATA2 mutation[J]. Leukemia, 2013, 27(11):2247-2248.
[10] Brambila-Tapia AJL, García-Ortiz JE, Brouillard P, et al. GATA2 null mutation associated with incomplete penetrance in a family with Emberger syndrome[J]. Hematology, 2017, 22(8):467-471.
[11] Ostergaard P, Simpson MA, Connell FC, et al. Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome)[J]. Nat Genet, 2011, 43(10):929-931.
[12] Hahn CN, Chong CE, Carmichael CL, et al. Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia[J]. Nat Genet, 2011, 43(10):1012-1017.
[13] Dickinson RE, Griffin H, Bigley V, et al. Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency[J]. Blood, 2011, 118(10):2656-2658.
[14] Saste AB, Jiang F, Arias-Stella J, et al. Emberger syndrome with concomitant GATA2, NPM1 and FLT3-ITD mutations in remission after allogeneic stem cell transplant[J]. Biol Blood Marrow Tr, 2016, 22(3):S208-S209.
[15] Rastogi N, Abraham RS, Chadha R, et al. Successful nonmyeloablative allogeneic stem cell transplant in a child with Emberger syndrome and GATA2 mutation[J]. J Pediatr Hematol Oncol, 2018, 40(6):e383-e388.
[16] Cuellar-Rodriguez J, Gea-Banacloche J, Freeman AF, et al. Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency[J]. Blood, 2011, 118(13):3715-3720.
