| Background and ObjectiveHereditary spherocytosis(HS)is characterized by anemia,jaundice,hepatosplenomegaly and cholelithiasis,which is one of the hemolytic diseases caused by erythrocyte membrane protein deficiency.HS is also an autosomal inherited disease with the highest incidence of 1/2,000 in Northern Europe and North America and a domestic incidence of 1/100,000.Because HS clinical manifestations vary in severity and symptoms are not typical,it is easy to miss the diagnosis and misdiagnosis in daily clinical work.It has been reported in the literature that the rate of missed diagnosis and misdiagnosis of HS in children is up to 69.2%.In recent years,there have been more and more reports on molecular genetics of HS in foreign countries,but there are few related studies in China,and most of them are based on individual cases.This study summarizes the clinical phenotype of children's HS,uses gene sequencing technology to detect disease-causing genes,and analyzes the molecular genetic characteristics of children with HS,In order to further improve the understanding of this disease,reduce missed diagnosis,misdiagnosis,and provide reference for clinical diagnosis and treatment.MethodsThe The clinical data of children with clinical diagnosis of HS from Henan Children's Hospital from June 2014 to June 2018 were retrospectively collected.A total of 43 children were eligible for diagnosis.Among them,20 children underwent genetic investigation and agreed to have peripheral blood samples taken for targeted capture or whole-exome second-generation sequencing.Sanger sequencing method was used to verify the suspected pathogenic loci and parent-of-origin analysis.Results1.General Information: Of the 43 children with confirmed HS,23 were males and 20 were females,with a male to female ratio of 1.15:1.The median age of onset is 1 year and 11 months(range,1 month to 10 years),with onset in infancy being the most common.Twenty-one(21/43,48.84%)children had a positive family history.2.Clinical features: Pallor(27/43,62.79%)was the most important first symptom,and the main clinical manifestations were anemia(36/43,83.72%),jaundice(35/43,81.40%),splenomegaly(33/43,76.74%),hepatomegaly(27/43,62.79%)and cholelithiasis(20/43,46.51%).3.Laboratory examination: Peripheral blood smear showed that the proportion of spherocytes was ?10% in 23 children(23/43,53.49%)and few or occasional spherocytes in 6 children(6/43,13.95%);bone marrow smear showed that the proportion of spherocytes was ?10% in 17 children(17/43,39.53%)and few or occasional spherocytes in 9 children(9/43,20.93%);erythrocyte osmotic fragility test was positive in 20 children(20/43,46.51%);acidified glycerol hemolysis test was positive in 16 children(16/43,37.21%);sucrose hemolysis test was performed in 9 children(9/43,20.93%);Coombs test and serum acidification hemolysis test showed no positive cases.4.Auxiliary examination: 33 cases(33/43,76.74%)with splenomegaly,27 cases(27/43,62.79%)with hepatomegaly,and 20 cases(20/43,46.51%)with cholelithiasis were evaluated for liver and spleen size and gallbladder status using ultrasound.5.Genetic test results: Twenty children underwent genetic testing,of which 13 children had heterozygous variants on three genes(ANK1,SPTB,and SPTA1)that were pathogenic or suspected to be pathogenic,eight were ANK1 variants,four were SPTB variants,and one was SPTA1 variant.Of the 13 novel variants,12 were unreported novel variants except for one inherited from the mother.6.Treatment results: The mean hemoglobin of the children increased from 78.24 ± 14.47 g/L to 88.69 ± 11.22 g/L after blood transfusion;the mean hemoglobin of the children after surgical splenectomy increased from 75.71 ± 9.96 g/L to 116.00 ± 5.54 g/L before and after surgery,and the difference between the two groups was statistically significant(P < 0.05).Conclusions1.The child developed progressive anemia and splenomegaly in infancy should consider the possibility of HS.It is recommended to complete HS-related examinations as early as possible to confirm the diagnosis at an early stage.2.Peripheral blood and/or bone marrow smears with spherocytosis and positive family history are reliable basis for the diagnosis of HS,and thirteen patients were genetically diagnosed to provide a basis for next-child genetic counseling;11 new variants were found in ANK1,SPTB,and SPTA1 genes,extending HS mutational profiles.3.Blood transfusions may be used to improve anemia in children with mild HS,and surgical splenectomy is recommended as early as possible for severe children in order to improve long-term prognosis. |
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