Study of clinical characteristics and related gene mutations in children with hereditary spherocytosis / 中华实用儿科临床杂志

ABSTRACT

Objective:To analyze the clinical phenotypes and molecular genetic characteristics of hereditary spherocytosis (HS) in children.Methods:The clinical data of children with HS in the Affiliated Children′s Hospital of Zhengzhou University from June 2014 to June 2018 were collected and analyzed retrospectively.The peripheral blood samples of 20 children and their parents were collected and targeted capture or whole exon group sequencing was performed using the second generation sequencing technique, and the suspicious mutation sites were verified by Sanger sequencing.Results:A total of 43 pediatric patients (23 males, 20 female) were included in this study.The median age of onset of 1 year old and 11 months (1 month to 10 years old). Pallor (27/43 cases, 62.79%) was the main symptom.Typical clinical manifestations were anemia (36/43 cases, 83.72%), jaundice (35/43 cases, 81.40%), splenomegaly (33/43 cases, 76.74%), and hepatomegaly (27/43 cases, 62.79%). The proportion of spherical erythrocytes in peripheral blood of 23 cases (23/43 cases, 53.49%)≥ 0.1, and the proportion of spherical erythrocytes in bone marrow smears of 17 cases (39.53%) was ≥ 0.1, and 20 cases were positive in erythrocyte osmotic fragility test (20/43 cases, 46.51%). Comparison of 29 children before and after blood transfusion post-transfusion hemoglobin (Hb) [(88.69±11.22) g/L vs. (78.24±14.47) g/L], mean corpuscular volume (MCV) [(89.37±7.15) fL vs.(84.08±7.49) fL], mean corpuscular hemoglobin (MCH) [(29.12±2.70) pg vs.(27.36±1.95) pg], mean corpuscular hemoglobin corpuscular (MCHC) [(361.79±32.27) g/L vs.(356.31±31.43 ) g/L] were increased, and the total bilirubin (TB) level was lower after blood transfusion than before blood transfusion [(33.27±16.42) μmol/L vs.(41.58±15.40) μmol/L], the differences were statistically significant ( t=-3.538, -5.187, -5.412, -7.404, 2.527, all P<0.05). Seven children underwent splenectomy postoperative Hb[(116.00±5.54) g/L vs.(75.71±9.96) g/L], MCH[(29.87±1.62) pg vs.(24.61±1.65) pg], MCHC [(391.14±12.99) g/L vs.(315.14±51.99) g/L] all increased, the difference was statistically significant ( t=-9.234, -4.330, -4.031, all P<0.05). The Hb in the operation group was significantly higher than that in the blood transfusion group, including the treatment effect of operation was more significant ( t=-9.247, P<0.05). Thirteen pathogenic mutations (11 new mutations not reported) were detected in 3 genes ( ANK1, SPTB and SPTA1) in 13 children, 8 of who were mutations in ANK1, 4 cases of which were mutations in SPTB and 1 case of which was mutation in SPTA1.Among the 13 mutations, 12 cases were de novo except one inherited from the mother. Conclusions:Anemia and pallor are the initial symptoms of HS in children.Blood transfusion can temporarily improve the symptoms of anemia and jaundice.Splenectomy is an effective and fundamental treatment.The gene diagnosis of 13 pediatric patients got gene diagnosis, which provided basis for genetic consultation of the next fetus.Eleven new mutations were found in ANK1, SPTB, SPTA1 genes, which exten-ded the gene mutation spectrum of HS.