Cases Of Hereditary Spherocytosis Research Articles

Enhanced Recovery after Surgery Applied to Pediatric Laparoscopic Cholecystectomy for Simple Cholelithiasis: Feasibility and Teaching Insights.

Same-day discharge after a cholecystectomy is a common practice in the adult population and has been demonstrated as safe and viable for children as well. However, there is a lack of comprehensive teaching models for pediatric cholecystectomy. Drawing inspiration from standardized outpatient procedures, this study aimed to assess the clinical outcomes and feasibility of teaching programs and an Enhanced Recovery After Surgery (ERAS) protocol following ambulatory laparoscopic cholecystectomy in pediatric patients. In 2015, an ERAS pathway for laparoscopic cholecystectomy (LC) was implemented, focusing on admission procedures, surgery timing, anesthetic choices, analgesia, postoperative feeding, mobilization, and pain assessment. Day-case surgery was not applicable for acute cholecystitis, choledochal lithiasis, sickle cell disease, and hereditary spherocytosis cases. The protocol was employed for a group of attending surgeons and fellows, as well as a group of residents under the supervision of experienced surgeons. A retrospective analysis was conducted to evaluate the feasibility and effectiveness of ambulatory cholecystectomy in children and its utilization in training pediatric surgical trainees. Between 2015 and 2020, a total of 33 patients were included from a cohort of 162 children who underwent LC, with 15 children operated on by senior surgeons and 18 by young surgeons. The primary diagnoses were symptomatic gallbladder lithiasis (n = 32) and biliary dyskinesia (n = 1). The median age at the time of surgery was 11.3 years (interquartile range (IQR) 4.9-18), and the median duration of surgery was 54 min (IQR 13-145). One intraoperative complication occurred, involving gallbladder rupture and the dissemination of lithiasis into the peritoneal cavity. Three patients (9%) required an overnight stay, while no postoperative complications or readmissions within 30 days were observed. ERAS was successfully implemented in 30 patients (91%). No significant differences in surgical outcomes were noted between senior and young surgeons. At an average follow-up of 55 months, no long-term sequelae were identified. These findings align with the current trend of increasing use of outpatient laparoscopic cholecystectomy and underscore its feasibility in the pediatric population. The application of a structured ERAS protocol appears viable and practical for training the next generation of pediatric surgeons. Level III.

Membrane Protein Detection and Morphological Analysis of Red Blood Cells in Hereditary Spherocytosis by Confocal Laser Scanning Microscopy.

In hereditary spherocytosis (HS), genetic mutations in the cell membrane and cytoskeleton proteins cause structural defects in red blood cells (RBCs). As a result, cells are rigid and misshapen, usually with a characteristic spherical form (spherocytes), too stiff to circulate through microcirculation regions, so they are prone to undergo hemolysis and phagocytosis by splenic macrophages. Mild to severe anemia arises in HS, and other derived symptoms like splenomegaly, jaundice, and cholelithiasis. Although abnormally shaped RBCs can be identified under conventional light microscopy, HS diagnosis relies on several clinical factors and sometimes on the results of complex molecular testing. It is specially challenging when other causes of anemia coexist or after recent blood transfusions. We propose two different approaches to characterize RBCs in HS: (i) an immunofluorescence assay targeting protein band 3, which is affected in most HS cases and (ii) a three-dimensional morphology assay, with living cells, staining the membrane with fluorescent dyes. Confocal laser scanning microscopy (CLSM) was used to carry out both assays, and in order to complement the latter, a software was developed for the automated detection of spherocytes in blood samples. CLSM allowed the precise and unambiguous assessment of cell shape and protein expression.

Five Years’ Experience with Gene Panel Sequencing in Hereditary Hemolytic Anemia Screened by Routine Peripheral Blood Smear Examination

Hereditary hemolytic anemia (HHA) is defined as a group of heterogeneous and rare diseases caused by defects of red blood cell (RBC) metabolism and RBC membrane, which leads to lysis or premature clearance. The aim of this study was to investigate individuals with HHA for potential disease-causing variants in 33 genes reported to be associated with HHA. A total of 14 independent individuals or families diagnosed with suspected HHA, and in particular, RBC membranopathy, RBC enzymopathy, and hemoglobinopathy, were collected after routine peripheral blood smear testing. A custom designed panel, including the 33 genes, was performed using gene panel sequencing on the Ion Torrent PGM™ Dx System. The best candidate disease-causing variants were confirmed by Sanger sequencing. Several variants of the HHA-associated genes were detected in 10 out of 14 suspected HHA individuals. After excluding those variants predicted to be benign, 10 pathogenic variants and 1 variant of uncertain significance (VUS) were confirmed in 10 individuals with suspected HHA. Of these variants, the p.Trp704Ter nonsense variant of EPB41 and missense p.Gly151Asp variant of SPTA1 were identified in two out of four hereditary elliptocytoses. The frameshift p.Leu884GlyfsTer27 variant of ANK1, nonsense p.Trp652Ter variant of the SPTB, and missense p.Arg490Trp variant of PKLR were detected in all four hereditary spherocytosis cases. Missense p.Glu27Lys, nonsense p.Lys18Ter variants, and splicing errors such as c.92 + 1G > T and c.315 + 1G > A within HBB were identified in four beta thalassemia cases. This study provides a snapshot of the genetic alterations in a cohort of Korean HHA individuals and demonstrates the clinical utility of using gene panels in HHA. Genetic results can provide precise clinical diagnosis and guidance regarding medical treatment and management for some individuals.

A Novel SPTA1 Mutation in a Patient with Hereditary Spherocytosis without a Family History and Coexisting Gilbert's Syndrome.

Most patients with hereditary spherocytosis (HS) have a family history of disease, while those without such a history are difficult to diagnose. We herein report a case of HS with no family history harboring a novel heterozygous mutation of SPTA1, c.2161 G>A (p.E721K), and a homozygous polymorphism of UGT1A1*6. In silico analyses suggested that the mutation might contribute to the pathogenesis of HS. The coexistence of HS and Gilbert's syndrome increases the risk of gallstones. Therefore, splenectomy, alone or in combination with cholecystectomy, is recommended. The determination of genetic diathesis provides useful information for the management of hemolytic anemia.

Utility of Cryohemolysis Test in the Diagnosis of Hereditary Spherocytosis.

Diagnosis of Hereditary spherocytosis (HS) often requires time-consuming and/or expensive tests. Cryohemolysis test (CHT) is a simple and easy to perform test with high predictive value for HS diagnosis. In this prospective study, we evaluated the diagnostic utility of CHT for the diagnosis of HS. We included 60 suspected HS patients, 18 patients with Autoimmune hemolytic anemia (AIHA) and 120 healthy controls. Among the 60 suspected cases, there were 36 HS cases and 24 with other hemolytic anemias. The mean CHT (%) ± SD for controls, AIHA, other hemolytic anemias, and HS was 6.63 ± 2.79, 6.79 ± 4.36, 6.61 ± 2.76 and 26.7 ± 8.9, respectively. The CHT % was significantly higher in HS group when compared to controls (p = < 0.0001), AIHA (p = < 0.0001) and other hemolytic anemia groups (p = < 0.0001). At a CHT cut off of > 18.3%, the sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of HS in our study were 97.1%, 94.4%, 97.2% and 90.3%, respectively. CHT is a simple and sensitive test for the diagnosis of HS but remains underutilized. The addition of CHT in the diagnostic workup of HS will be very useful, especially in a resource limited setting.

A novel variant of SLC4A1 for hereditary spherocytosis in a Chinese family: a case report and systematic review

BackgroundThe incidence of hereditary spherocytosis (HS) is approximately 1:2000 in the western population, while it is much lower in the Chinese population. It is difficult to make a definite diagnosis due to the variable genotypic features and the lack of well-documented evidence for HS patients. Gene sequence examination is helpful for clear diagnosis.Case presentation:We presented the case of a 29-year-old male HS patient with skin yellowness, anorexia, and cholecystolithiasis as the first manifestations. Laboratory examination of the patient and his parents showed a mild reduction in hemoglobin and mean corpuscular hemoglobin concentration, increased reticulocytes, and promotion of indirect bilirubin in the patient and his father. Furthermore, small globular red blood cells with increased osmotic fragility were observed. In particular, the eosin-5’-maleimide binding test provided the strong evidence that band 3 protein was deleted in the erythrocyte membrane. Next-generation sequencing (NGS) and Sanger sequencing further demonstrated a heterozygous nonsense variant (exon16, c.G1985A: p.W662X) in SLC4A1, inherited from his father. Thus, the patient was diagnosed with HS, and then was effectively treated. After splenectomy, the anemia was relieved without any obvious unpleasant side effects.ConclusionWe report an extremely rare case of HS in China that presented with hereditary hemolytic anemia with band 3 deletion resulting from a novel variant of SLC4A1, and systematically review a large number of related literatures. This study, therefore, significantly contributes to the literature on HS.

A case report of hereditary spherocytosis (HS): Approach to diagnosis and management of HS

Hereditary spherocytosis (HS) is a type of congenital hemolytic anemia, in which heterogeneous alterations in one of the six genes that encode for proteins involved in vertical associations which tie the red blood cell (RBC) membrane skeleton to the lipid bilayer causesdysfunction or deficiency of cell membrane protein resulting in spherical-shaped, hyper- dense, and poorly deformable RBCs with a shortened life span. We report a case of HS in a 2-month-old female who presented with severe anemia, jaundice, and hepatosplenomegaly.The peripheral blood smear showed spherocytosis and reticulocytosis. The osmotic fragility was positive and direct antiglobin test was negative. The osmotic fragility test and direct antiglobulin test were positive. She was managed with packed RBCs (PRBCs) transfusionand folic acid supplementation.

The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper.

The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper.

A Case of Hereditary Spherocytosis in a Patient who Received Chemotherapy Safely after Splenectomy

症例は57歳，女性．20歳時に遺伝性球状赤血球症（HS）と診断され，溶血性貧血のため定期的に輸血をしていた．左乳房腫瘤自覚を機に左乳癌cT2N0M0 Stage IIAと診断され，手術を施行した．術後診断はpT2N1M0 Stage IIBとなり，術後補助療法として化学療法・内分泌療法・温存乳房照射を予定した．術後化学療法を開始後，貧血・総ビリルビン値上昇を認め，HSによる溶血が悪化したと考えられ，化学療法は中止となった．術後2年で肝臓・脾臓に転移巣を認め，今後化学療法を行う可能性を考慮し，溶血の予防策として脾臓摘出術を行った．その後，内分泌療法施行するも肝臓，骨，リンパ節に転移が出現したため，化学療法施行とした．溶血性貧血の進行はなく，安全に化学療法を施行できた．われわれは，脾臓摘出術後に安全に乳癌再発に対する化学療法が実施可能となったHSの1例を経験したので，若干の文献的考察を加えて報告する．

Hereditary Spherocytosis in PregnancyA Case Report

Hereditary Spherocytosis (HS) is the most common inherited red cell membrane disorder included under intracorpuscular defect. HS has both autosomal dominant and autosomal recessive inheritance. The disease may be mild, moderate or severe and requires a multidisciplinary approach for its management during pregnancy. Hereby, authors discusses a case of a 30-year-old female G2P1L1 at 34 weeks+4 days presented with anaemia not responding to iron therapy since first trimester. Peripheral blood smear revealed red blood cell’s were normocytic and normochromic. Spherocytes were seen with mild polychromatophilia and diagnosed as a case of HS and its management was done with haematological support.

Identification of a De Novoc.1000delA ANK1 mutation associated to hereditary spherocytosis in a neonate with Coombs-negative hemolytic jaundice-case reports\xa0and review of the literature\xa0

BackgroundTo strengthen the understanding of Hereditary Spherocytosis (HS) and determine the disease-causing mutation present with neonatal jaundice. HS is a hemolytic condition resulting from various erythrocyte membrane defects. Many different mutations result in HS, including mutations in ANK1.Case presentationA term neonate presented at ten hours with severe jaundice requiring exchange transfusion. At two months he was hospitalized due to repeated pallor and anemia requiring blood transfusions. Using next-generation sequencing, we discovered the responsible mutation in the proband but not in his parents; a heterozygous nucleotide variation of c.1000delA (p.1334Sfs*6) in ANK1. Thus hereditary spherocytosis was diagnosed.ConclusionsGenetic detection is an important means of discovering the cause of hemolytic anemia in neonates and infants where routine diagnostic tests are unrevealing. We found a novel de novo mutation, c.1000delA (p.1334Sfs*6) in ANK1 that might account for other cases of HS in the Chinese population.

A Case of Hereditary Spherocytosis with Associated Hypersplenism

Hereditary spherocytosis is a less common blood disorder where the cytoskeleton of red blood cell is defective due to mutation in their structural proteins and consequently the cell becomes spherical and fragile and destructed earlier than their usual life span. The case was a 25 year old male who had been suffering from continuous lethargy, weakness and abdominal pain for 2 years. After thorough clinical and laboratory exams he had spherical red blood cells in peripheral blood film and elevated fragile osmotic test, therefore he diagnosed with hereditary spherocytosis. Hereditary spherocytosis an infrequent red blood cell disorder where the cells become round and easily destructed and osmotic fragile test helps for confirmed diagnosis.

Long-Term Evaluation of the Outcomes of Subtotal Laparoscopic and Robotic Splenectomy in Hereditary Spherocytosis.

Hereditary spherocytosis (HS) is a common inherited disease affecting the erythrocyte membrane. Total splenectomy (TS) is effective in reducing hemolysis and decreasing the need of transfusions, but total removal of the spleen represents a potential risk factor for infectious and non-infectious complications. On the other hand, subtotal splenectomy (STS) could be an alternative therapy for HS. The aim of this study is to establish which surgical approach has the best outcome in HS. All patients (n = 63) receiving splenectomy for HS between 2002 and 2016 from one institution were retrospectively reviewed. Hemoglobin and reticulocytes levels during preoperative and postoperative follow-up periods were compared. Additionally, a meta-analysis was performed analyzing data regarding hemoglobin and reticulocytes levels from several available studies. At 1-year follow-up, our clinical data showed that mean hemoglobin levels increased after TS from (mean ± SD) 9.77 ± 1.82 to 11.88 ± 2.08g/dl, while after STS from 8.98 ± 1.66 to 11.87 ± 1.38g/dl. At 3-year and 5-year follow-up after TS, we observed an increase from 9.77 ± 1.82 to 13.59 ± 2.03 and 13.46 ± 1.64g/dl, respectively. At 3-year and 5-year follow-up after STS in our cohort, we observed an increase from 8.98 ± 1.66 to 13.21 ± 1.95 and 13.68 ± 1.65g/dl, respectively. The meta-analysis (for a follow-up period of 1year) showed that the hemoglobin levels increased with 2.61g/dl (95% CI 2.15-3.08g/dl; p < 0.001) after TS, and with 1.67g/dl (95% CI 1.25-2.10g/dl; p < 0.001) after STS. We conclude that subtotal and minimally invasive splenectomy could be considered as the first line of treatment in severe HS cases, especially in children.

A clinical and experimental study of adult hereditary spherocytosis in the Chinese population.

Hereditary spherocytosis (HS) is often misdiagnosed due to lack of specific diagnostic methods. Our study summarized clinical characteristics and described the diagnostic workflow for mild and moderate HS in Chinese individuals, using data from 20 adults, 8 of whom presented a familial history for HS. We used scanning electron microscopy (SEM) to diagnose HS. We observed reduced eosin maleimide fluorescence activity (5.50 mean channel fluorescence (MCF) units) in the 10 cases of HS, which differed significantly when compared with 10 normal adults (15.50 units), iron deficiency anemia (15.50 MCF units), and megaloblastic anemia (12.00 MCF units) values (P < .05). Next generation sequencing results revealed that 9 out of 10 patients were found to have mutations in the spectrin alpha chain (SPTB), anchor protein (ANK1), and SLC4A1 genes. These mutations were not reported in the Human Gene Mutation Database (HGMD), 1000 human genome, ExAC, and dbSNP147 databases. Splenectomy proved to be beneficial in alleviating HS symptoms in 10 cases. It was found that for the diagnosis of HS, SEM and next generation gene sequencing method proved to be more ideal than red blood cell membrane protein analysis using sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blotting.

A tetranucleotide deletion in the ANK1 gene causes hereditary spherocytosis; a case of misdiagnosis

Hereditary spherocytosis is a congenital red blood cell disorder. Typical clinical manifestations include anemia, jaundice and splenomegaly, which overlap with the thalassemia phenotype. Therefore, in high prevalence thalassemia regions, hereditary spherocytosis cases are often misdiagnosed. Here, a case once diagnosed as thalassemia, based on preliminary clinical examinations, underwent genetic testing in our laboratory, where analysis of globin gene mutations proved negative. We conducted both clinical and genetic analyses on the patient and his family. We collected clinical data, performed erythrocyte membrane protein analysis by SDS-PAGE and sequenced the ANK1 gene. We also investigated pathogenic mechanisms through cDNA sequencing and literature studies. From patient clinical data, we diagnosed the patient with moderate to severe hereditary spherocytosis, rather than thalassemia. SDS-PAGE data showed that Ankyrin protein expression was reduced. Sequencing of genomic DNA identified a frameshift mutation (ANK1:c.2394_2397del CAGT). cDNA sequencing showed that the expression of a mutant allele was significantly decreased. Our study corrected a clinical misdiagnosis and confirmed the diagnosis of hereditary spherocytosis in this patient. Identification of such causative mutations is important for accurate downstream patient therapy and is critically important for the prevention/detection of another affected birth. Additionally, the disruption of mRNA transcribed from the mutant allele resulted in a significant reduction in Ankyrin expression and was speculatively considered the pathogenic mechanism behind this mutation.

Clinical utility of targeted gene enrichment and sequencing technique in the diagnosis of adult hereditary spherocytosis

The present study aimed to use the targeted capture and sequencing technique to diagnose adult hereditary spherocytosis (HS). These results were compared with clinical features and laboratory examinations to explore the diagnosis of HS. Whole blood and clinical data from ten patients with HS were collected. Genomic DNA was extracted, and a library was prepared. Exomes of patients with ten HS-related genes encoding red cell membrane skeleton protein were captured and sequenced. Bioinformatics analyses were carried out throughout the 1000 Genomes Project, ExAC, dbSNP147, and 1000 Normal Han Population databases. Gene mutations were found in 9 out of 10 cases of HS. Our data validation showed 90% specificity. Three types of gene mutations were found, including 6 cases of SPTB, 3 cases of ANK1, and 2 cases of SLC4A1. There were 4 mutation forms, including nonsense mutation, missense mutation, shear mutation, and code shift mutation, all of which were new, heterozygous mutations. These variations were predicted to be pathogenic in four databases. Our data demonstrate that targeted gene enrichment and sequencing methods were an efficient tool for determining genetic etiologies of red blood cell (RBC) membrane disorders and can facilitate accurate diagnosis and genetic counseling. They are also in good agreement with the clinical results.

Hereditary Spherocytosis : A Clinical Experience

Although hereditary spherocytosis is a common cause of hemolytic anemia among whites of Northern European descent, it is uncommon in Asia. In the past 8.5 years (from December 1978 to June 1987), we found only six cases of hereditary spherocytosis. They were 3 males and 3 females, and their ages ranged from 3 months to 8 years, with a mean age of 3.3 years. The most common presenting complaint was anemia (6 cases) followed by jaundice (4 cases) and splenomegaly (4 cases). Other symptoms were fever, abdominal pain and hepatomegaly. The mean hemoglobin concentration of these patients was 7.5 g/dl, in which 2 patients had severe anemia (less than 6 g/dl). Reticulocyte count ranged from 1.9% to 10% (mean 5.9%). All patients were found to have spherocytosis in their peripheral blood smears and an increased red blood cell fragility. Splenectomy was performed in one patient. There was no significant complication after operation in a 7-month follow up. The clinical manifestation returned to normal and the mean hemoglobin concentration increased. The existence of hereditary spherocytosis could not be proven in almost all parents of the patients. Based on this fact, is 'congenital spherocytosis' a more suitable term instead of hereditary spherocytosis?

Hereditary spherocytosis and allied disorders

Hereditary spherocytosis and allied disorders

PS1200 IDENTIFICATION OF MUTATIONS IN RED CELL MEMBRANOPATHIES USING NGS‐TARGETED SEQUENCING PANEL

Background:Red cell membranopathies refers to genetically and phenotypically heterogenous disorders due to defects in red cell membrane and skeletal proteins. Phenotypes vary from severe transfusion‐dependent hemolytic anemia to fully compensated hemolysis. Causative genes implicated in RBC membranopathies are numerous, making a gene‐by‐gene approach time consuming, expensive and labor intensive. Use of Next Generation Sequencing (NGS) targeted sequencing panel can expedite the molecular diagnosis after routine laboratory tests.Aims:This study aimed at defining a strategy for effective diagnosis of RBC membrane defects and identification of pathogenic mutations associated with the disease.Methods:Patients with clinical symptoms of hemolytic anemia, jaundice, hepatosplenomegaly and some requiring frequent blood transfusions were recruited in this study. Blood was collected from the patients after informed consent. Peripheral blood smear examination and flow cytometric based EMA binding test were performed and identification of mutations in red cell membrane proteins was done using NGS‐targeted sequencing panel. The relationship between gene mutations and clinical phenotypes was analyzed by In silico prediction tools such as SIFT, Polyphen2.Results:We identified mutations in 21 cases of Hemolytic Anemia (HA) in membrane protein‐coding genes using NGS‐targeted sequencing panel. Five Hereditary Spherocytosis (HS) patients were diagnosed with mutations in ankyrin (ANK1) gene, 3 patients with alpha spectrin (SPTA1) gene and 4 patients with beta spectrin (SPTB) gene. Band 3 (SLC4A1) gene mutations was identified in two HS cases and in 2 with dRTA cases. Five patients showed mutation in PIEZO1 gene causing Hereditary xerocytosis (HX). Twelve novel mutations were found as shown in Table 1.Summary/Conclusion:RBC membranopathies showed highly varied etiology. Our experience demonstrates the high diagnostic yield of NGS for molecular diagnosis of RBC membrane disorders associated with defects in large genes. Timely detection of the disorder not only offers therapeutic benefits for our patients but is likely to help in genetic counseling and future antenatal diagnosis, if required.image

PB1973 CONTRIBUTION OF NGS IN THE DIAGNOSIS OF HEREDITARY SPHEROCYTOSIS: CASE REPORT

Background:Hereditary spherocytosis (HS) is the most frequent cause of non‐immune haemolytic anaemia (HA) among individuals of Northern European ancestry; its estimated prevalence is 1:2000. HS results from various molecular defects leading to decreased production or abnormality of one or more red blood cell (RBC) membrane proteins i.e., ankyrin, protein 4.2, band 3 and spectrin. The majority of HS cases (75%) are inherited in an autosomal dominant manner. Especially because of the spherical shape, RBCs are trapped in the spleen and have a shortened life span. Among other factors, according to the importance of the deficiency or protein abnormality it conducts to a clinical expression that may range from asymptomatic to severe chronic HA. Most often a phenotypic diagnosis can be made but next‐generation gene sequencing (NGS) has a place in difficult cases i.e. unsolved cases of HA, transfusion prior to diagnosis and discrepancy between clinical phenotype and diagnosis.Aims:We report here the case of a 18‐year‐old patient with a suspected HS, prominent splenomegaly and unknown personal or family history.Methods:Case report:The patient complained of fatigue for several months and grade 2 dyspnea. In the past, he repeatedly presented with biliary colic pain. He apparently had no personal or family medical history. Two years ago, he nevertheless had jaundice secondary to haemolytic anaemia. The evolution was spontaneously favourable and no further investigation was undertaken. He has a twin brother and a 20‐year‐old sister, both in good health. The clinical examination found a prominent splenomegaly. Haemoglobinopathy and most frequent RBC enzyme deficiencies were excluded. Given the high clinical suspicion of HS, his parents and siblings (although asymptomatic) were screened for HS.Results:The main biological data are reported in the Table 1.Molecular genetic analyses were performed: NGS targeted sequencing panel, containing panel 40 genes associated to haemolytic anemia, and confirmation by Sanger identified a nonsense mutation on the cytoplasmic domain of Band3. The mutation is novel and drastic; it causes a stop codon at 75 residues. The mutation is transmitted by the mother. NGS targeted sequencing analysis did not demonstrate any other abnormalities that could explain the phenotypic variability observed in the propositus and his mother.Given the profound anaemia associated to the voluminous spleen (main diameter of 25 cm by CT‐scan evaluation) and given the presence of symptomatic gallstones, the patient underwent a splenectomy and a cholecystectomy. After the procedure, he recovered from fatigue and the haemoglobin level returned to normal with no signs of residual haemolysis.Summary/Conclusion:This case reports a HS related to a new nonsense mutation in SLC4A1. The transmission is autosomal dominant but the penetrance is heterogeneous within the same family.image