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Journal of Minimal Access Surgery Jan 2024A true left-sided gall bladder (LSG) is a rare finding, is mostly discovered incidentally and often presents with symptoms similar to those of a normally positioned gall...
A true left-sided gall bladder (LSG) is a rare finding, is mostly discovered incidentally and often presents with symptoms similar to those of a normally positioned gall bladder. The diagnosis in most cases is intraoperative. The surgical technique is frequently difficult, with an increased risk of intraoperative injuries and conversion to open surgery. In this case report, we describe a rare scenario of a young male with hereditary spherocytosis who presented with jaundice and splenomegaly. The diagnosis of LSG was made by chance during pre-operative imaging. The patient was successfully managed with a splenectomy and a cholecystectomy via the minimal access approach in the same setting.
PubMed: 37148108
DOI: 10.4103/jmas.jmas_347_22 -
Indian Journal of Thoracic and... May 2023Inflammatory myofibroblastic tumors are a rare subset of lung lesions in the adult age group. They pose a diagnostic challenge as they present with non-specific...
Inflammatory myofibroblastic tumors are a rare subset of lung lesions in the adult age group. They pose a diagnostic challenge as they present with non-specific findings. We report a 27-year-old female with an inflammatory myofibroblastic tumor on a background of hereditary spherocytosis.
PubMed: 37124597
DOI: 10.1007/s12055-022-01464-6 -
Indian Pediatrics Apr 2023
Topics: Humans; Spherocytosis, Hereditary; Anemia, Hemolytic; Ankyrins; Liver Diseases
PubMed: 37002847
DOI: No ID Found -
Biomedicines Mar 2023Hereditary spherocytosis (HS) refers to the group of the most frequently occurring non-immune hereditary hemolytic anemia in people of Caucasian central or northern...
Hereditary spherocytosis (HS) refers to the group of the most frequently occurring non-immune hereditary hemolytic anemia in people of Caucasian central or northern European ancestry. HS is mainly associated with pathogenic variants of genes encoding defects in five membrane proteins, including anion exchanger 1 encoded by the gene. In this study, in a family affected with HS, we identified a hitherto unreported AE1 defect, variant p.G720W. The result of it is most likely the HS phenotype. Molecular dynamics simulation study of the AE1 transmembrane domain may indicate reasonable changes in AE1 domain structure, i.e., significant displacement of the tryptophan residue towards the membrane surface connected with possible changes in AE1 function. The WES analysis verified by classical sequencing in conjunction with biochemical analysis and molecular simulation studies shed light on the molecular mechanism underlying this case of hereditary spherocytosis, for which the newly discovered AE1 variant p.G720W seems crucial.
PubMed: 36979763
DOI: 10.3390/biomedicines11030784 -
Scientific Reports Mar 2023Iron homeostasis and dyserythropoiesis are poorly investigated in pyruvate kinase deficiency (PKD), the most common glycolytic defect of erythrocytes. Herein, we studied...
Iron homeostasis and dyserythropoiesis are poorly investigated in pyruvate kinase deficiency (PKD), the most common glycolytic defect of erythrocytes. Herein, we studied the main regulators of iron balance and erythropoiesis, as soluble transferrin receptor (sTfR), hepcidin, erythroferrone (ERFE), and erythropoietin (EPO), in a cohort of 41 PKD patients, compared with 42 affected by congenital dyserythropoietic anemia type II (CDAII) and 50 with hereditary spherocytosis (HS). PKD patients showed intermediate values of hepcidin and ERFE between CDAII and HS, and clear negative correlations between log-transformed hepcidin and log-EPO (Person's r correlation coefficient = - 0.34), log-hepcidin and log-ERFE (r = - 0.47), and log-hepcidin and sTfR (r = - 0.44). sTfR was significantly higher in PKD; EPO levels were similar in PKD and CDAII, both higher than in HS. Finally, genotype-phenotype correlation in PKD showed that more severe patients, carrying non-missense/non-missense genotypes, had lower hepcidin and increased ERFE, EPO, and sTFR compared with the others (missense/missense and missense/non-missense), suggesting a higher rate of ineffective erythropoiesis. We herein investigated the main regulators of systemic iron homeostasis in the largest cohort of PKD patients described so far, opening new perspectives on the molecular basis and therapeutic approaches of this disease.
Topics: Humans; Hepcidins; Iron; Erythropoietin; Anemia; Anemia, Hemolytic, Congenital Nonspherocytic; Erythropoiesis; Receptors, Transferrin
PubMed: 36927785
DOI: 10.1038/s41598-023-31571-2 -
World Journal of Clinical Cases Feb 2023The aim of the present study was to enhance understanding of the diagnosis and treatment of atypical hereditary spherocytosis (HS), and to broaden the diagnostic...
BACKGROUND
The aim of the present study was to enhance understanding of the diagnosis and treatment of atypical hereditary spherocytosis (HS), and to broaden the diagnostic thoughts of physicians for patients with jaundice.
CASE SUMMARY
A 28-year-old male presented with jaundice, bile duct stone, and splenomegaly, but without anemia. Other causes of jaundice were excluded, and gene sequencing revealed a novel heterozygous variant of c.1801C>T (p.Q601X) in exon 14 of the SPTB (NM_01355436) gene on chromosome 14 (chr14: 65260580) in the patient's blood; the biological parents and child of the patient did not have similar variants. A splenectomy was performed on the patient and his bilirubin levels returned to normal after surgery. Thus, a novel gene variant causing HS was identified. This variant may result in the truncation of β-hemoglobin in the erythrocyte membrane, leading to loss of normal function, jaundice, and hemolytic anemia. The clinical manifestations of the patient were hyperjaundice and an absence of typical hemolysis during the course of the disease, which caused challenges for diagnosis by the clinicians.
CONCLUSION
Following a definitive diagnosis, genetic testing and response to treatment identified a gene variant site for a novel hemolytic anemia.
PubMed: 36926142
DOI: 10.12998/wjcc.v11.i6.1349 -
Journal of Clinical Medicine Mar 2023We report a case of severe anemia caused by complex hereditary spherocytosis (HS) and X-linked sideroblastic anemia (XLSA) with two mutations in the spectrin beta ( and...
We report a case of severe anemia caused by complex hereditary spherocytosis (HS) and X-linked sideroblastic anemia (XLSA) with two mutations in the spectrin beta ( and 5-aminolevulinic acid synthase () genes. The proband was a 16-year-old male with severe jaundice and microcytic hypochromic anemia since his childhood. He had more severe anemia requiring erythrocyte transfusion, and had no response to vitamin B treatment. Next-generation sequencing (NGS) revealed double heterozygous mutations, one in exon 19 (c.3936G > A:p.W1312X) of the gene and another in exon 2 (c.37A > G:p.K13E) of the gene, and confirmed again by Sanger sequencing. The mutation of (c.37A > G) is inherited from his asymptomatic heterozygous mother, causing amino acid p.K13E, and the mutation has not yet been reported. The mutation of (c.3936G > A) is a nonsense mutation, leading to a premature termination codon in exon 19, and the mutation in the gene is not found in any of his relatives, which indicates a de novo monoallelic mutation. Conclusions: The double heterozygous mutations in the and genes lead to the joint occurrence of HS and XLSA in this patient, and are implicated in the more severe clinical phenotypes.
PubMed: 36902777
DOI: 10.3390/jcm12051990 -
Diagnostics (Basel, Switzerland) Feb 2023Hereditary 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...
BACKGROUND
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.
METHODS
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.
RESULTS
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 and missense p.Gly151Asp variant of were identified in two out of four hereditary elliptocytoses. The frameshift p.Leu884GlyfsTer27 variant of , nonsense p.Trp652Ter variant of the , and missense p.Arg490Trp variant of 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 were identified in four beta thalassemia cases.
CONCLUSIONS
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.
PubMed: 36832257
DOI: 10.3390/diagnostics13040770 -
Frontiers in Genetics 2023Hereditary spherocytosis (HS) is an autosomal dominant (AD) and autosomal recessive (AR) disorder that is mostly caused by mutations of the erythrocyte membrane-related...
Hereditary spherocytosis (HS) is an autosomal dominant (AD) and autosomal recessive (AR) disorder that is mostly caused by mutations of the erythrocyte membrane-related gene . Clinical and genetic testing data of 17 HS children with gene mutations were retrospectively collected. Clinical manifestations and phenotypic analysis of HS were summarized based on our experience and literature review. A total of 17 mutations of the gene were identified from 17 probands (12 sporadic cases and five familial cases), including 15 novel mutations and two previously reported ones. Among the 15 novel variants of , there were four non-sense mutations, four frameshift mutations, three splicing mutations, three missense mutations and one in-frame deletion of three amino acids. In the present study, HS patients with mutations in membrane binding domains had significantly lower hemoglobin (Hb) levels and higher total bilirubin (T-Bil) levels than those with mutations in regulatory domains. After reviewing and analyzing all available published reports of Chinese HS patients carrying ANK1 mutations in PubMed and Chinese journals, there were no significant differences in Hb, Ret and T-Bil between different mutation types or mutation regions. Mutations of the can be inherited or . Clinical manifestations of HS in children caused by mutations are similar to those of other types of hemolytic anemia. Our report expands the mutation spectrum of HS, thus providing references for clinical management and genetic counseling of HS.
PubMed: 36816036
DOI: 10.3389/fgene.2023.1088985