探讨遗传性球形红细胞增多症(HS)患儿的临床表现及诊断经过，并进行相关文献复习。

选择2018年4月，首都儿科研究所附属儿童医院收治的1例HS患儿为研究对象。采用回顾性分析方法，收集该例患儿的临床病例资料，并对其病史、相关实验室检查和基因检测结果进行分析。对国内外数据库中，儿童HS相关文献进行复习。本研究符合2013年修订的《世界医学协会赫尔辛基宣言》要求。

①本例患儿为女性，年龄为13岁8个月。患儿6岁时初次发病，以皮肤及巩膜黄染、乏力为主要表现。多次在其所居住地的县、市及省级医院就诊，均未被明确诊断。②于本院及外院主要实验室检查结果：外周血涂片检查显示，球形红细胞所占比例为9%～27%。胆红素检测显示，总胆红素为52.6～313.8 μmol/L，直接胆红素为8.2～14.6 μmol/L，间接胆红素为38.0～302.1 μmol/L，均异常增高。红细胞渗透脆性(EOF)试验显示，红细胞开始出现溶血时，EOF为0.68% NaCl(正常参考值为0.38%～0.46% NaCl)，完全溶血时EOF为0.44% NaCl(正常参考值为0.28%～0.32% NaCl)。③基因检测结果：患儿全外显子基因检测显示，红细胞血影蛋白β(SPTB)基因2号与3号外显子疑似杂合缺失，疾病表型为球形红细胞增多症2型(常染色体显性遗传)、椭圆形红细胞增多症3型(遗传方式不明确)、致死性或近致死性新生儿溶血性贫血(遗传方式不明确)。患儿父亲存在PIEZO1基因chr16-88804044位点杂合突变c.1118C>T(p.P373L)，其母亲未发现HS相关基因突变。④诊断及治疗：根据实验室检查及基因检测结果，该例患儿被确诊为HS。治疗建议：必要时进行脾切除术。2020年6月，患儿于当地医院进行脾切除术后，黄疸消失，但是出现轻度贫血。⑤文献复习结果：根据本研究制定的检索策略，共计检索到35篇关于HS患儿相关文献，其中7篇报道12例HS患儿发病与SPTB基因有关，SPTB基因不同位点突变患儿的临床表现不同。

HS患儿临床表现异质性大，易被临床漏诊、误诊。临床需结合患儿临床表现、家族病史、针对性实验室检查和基因检测结果，对该病患儿进行早诊断、早治疗，进而改善患儿预后。

To explore clinical manifestations and diagnosis in children with hereditary spherocytosis (HS), and review relevant literature.

A child with HS who was admitted to the Children′s Hospital Affiliated to Capital Institute of Pediatrics in April 2018 was selected as research subject. Retrospective analysis method was used to collect clinical case data, and analyze of her medical history, results of relevant laboratory examinations and genetic testing. Related literatures of children with HS in home and abroad databases were reviewed by strategies.This research was in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013.

①The child was a girl, aged 13 years and 8 months. She was 6 years old at first onset, with xanthochromia and icteric sclera, and fatigue as the main manifestations. She has repeatedly visited the county, city and provincial hospitals where she lives, but no definite diagnosis has been obtained. In April 2018, she visited the Children′s Hospital Affiliated to Capital Institute of Pediatrics. ②Main laboratory test results: the proportion of spherical red blood cells was 9% to 27% by peripheral blood smears. Concentrations of total bilirubin was 52.6-313.8 μmol/L, direct bilirubin was 8.2-14.6 μmol/L, and indirect bilirubin was 38.0-302.1 μmol/L which all were abnormally increased by bilirubin testing. At the beginning of hemolysis, erythrocyte osmotic fragility (EOF) was 0.68% NaCl (reference range: 0.38% to 0.46% NaCl), and 0.44% NaCl at complete hemolysis (reference range: 0.28% to 0.36% NaCl). ③Genetic testing results: a suspected heterozygosity loss in exons 2 and 3 of spectrin beta erythrocytic (SPTB) gene was detected and the disease phenotypes were spherocytosis type 2 (autosomal dominant), elliptocytosis type 3 (inherited mode unknown), and fatal or near-fatal neonatal hemolytic anemia (inherited mode unknown). Her father had a heterozygous mutation c. 1118C>T(p.373L) of PIEZO1 gene at chr16-88804044 site. ④Diagnosis and treatment: according to results of laboratory examination and genetic testing, the child was diagnosed as HS, and splenectomy was recommended if necessary. In June 2020, she underwent splenectomy in a local hospital, and after that, her jaundice disappeared and anemia was mild. ⑤Literature review results: a total of 35 pieces of HA related literature were reviewed, 12 cases of HS children reported in 7 pieces of literature were related to SPTB gene. The clinical manifestations of children with SPTB gene mutation at different sites were different.

Clinical manifestations of children with HS are highly heterogeneous and are easily missed diagnosed. Early definite diagnosis and treatment of HS depends on clinical manifestations, targeted laboratory examinations and genetic testing, so as to improve the prognosis of children with HS.